Archive for month: November, 2024

A recent study highlighted a significant link between elevated levels of hypersensitive C-reactive protein (hs-CRP) and the risk of developing non-alcoholic fatty liver disease (NAFLD) in non-obese individuals. With both NAFLD and obesity on the rise worldwide, NAFLD has become one of the most prevalent chronic diseases throughout the globe, often accompanied by elevated hs-CRP levels. Given that NAFLD can progress to more severe liver diseases, the findings published in the European Journal of Medical Research have valuable implications for early detection and preventive strategies, particularly in non-obese populations where the risk may often be underestimated.

The study analyzed data from 6,558 individuals who underwent physical exams between March and November 2017 to investigate the correlation between serum hs-CRP levels and NAFLD in non-obese people. Using multivariate logistic regression, the research assessed risk factors associated with NAFLD across participants aged 20 to 94 years, including 4,240 males and 2,318 females. Out of the total participants, 1,396 individuals were diagnosed with NAFLD by marking a prevalence rate of 21.3%. The data showed a stark difference in prevalence between genders where 24.9% of men were affected when compared to 14.7% of women. Statistical analysis confirmed a higher prevalence of NAFLD among males (χ² = 93.748, P < 0.001).

With further examination, the study revealed that several physiological factors were higher in NAFLD patients than in the control group. These factors included hs-CRP, age, waist circumference (WC), body mass index (BMI), systolic blood pressure, and diastolic blood pressure. Logistic regression analysis established that hs-CRP remains an independent risk factor for NAFLD, even when adjusted for other relevant variables. These results suggest that hs-CRP levels could serve as a valuable indicator of NAFLD risk in non-obese individuals which provides a clinical tool to improve risk prediction and screening in populations that may otherwise go undiagnosed.

These findings suggest a positive association between NAFLD prevalence and increasing hs-CRP levels in both men and women, irrespective of obesity. The elevated levels of hs-CRP observed in NAFLD patients reflect underlying inflammation, which is believed to play a role in the development and progression of the disease. This inflammation marker could be instrumental in identifying high-risk individuals who lack traditional risk factors such as obesity. Overall, the study emphasizes the need for healthcare practitioners to consider hs-CRP levels when assessing NAFLD risk, particularly in individuals who do not exhibit typical obesity-related symptoms.

Source:

Xia, G., Xu, Y., Zhang, C., Li, M., Li, H., & Chen, C. (2024). High levels of serum hypersensitive C-reactive protein are associated with non-alcoholic fatty liver disease in non-obese people: a cross-sectional study. In European Journal of Medical Research (Vol. 29, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s40001-024-02065-2

The nonhormonal drug elinzanetant showed substantial benefit for hot flashes, sleep disturbance, and quality of life in data from three randomized controlled trials presented at The Menopause Society 2024 Annual Meeting in Chicago. OASIS 1 and 2 trials were published in JAMA, and the OASIS 3 trial was presented as a poster at the conference. Recent research paper summarizes the findings from three randomized controlled trials (OASIS 1, 2, and 3) evaluating the efficacy and safety of the investigational drug elinzanetant for the treatment of vasomotor symptoms associated with menopause.

Elinzanetant Mechanism and Trial Design

Elinzanetant is a selective neurokinin receptor antagonist that targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons, which are thought to play a role in thermoregulation and hot flashes during menopause. The OASIS 1 and 2 trials enrolled postmenopausal women aged 40-65 years with at least 50 moderate to severe vasomotor symptoms per week. They were randomized to receive either 120 mg of oral elinzanetant or placebo once daily for 12 weeks, after which the placebo group switched to elinzanetant for the final 14 weeks.

Findings from Elinzanetant Trials

The results showed that elinzanetant led to a significant reduction in the daily frequency and severity of vasomotor symptoms compared to placebo. Elinzanetant also significantly improved sleep disturbance and quality of life measures. The OASIS 3 trial, which assessed elinzanetant for 1 year, supported the findings from the earlier trials, demonstrating sustained efficacy over a longer duration.

Safety Considerations

Regarding safety, the most commonly reported adverse events with elinzanetant were headache, fatigue, and sleepiness. A higher proportion of elinzanetant users discontinued the study compared to placebo. However, there were no serious adverse events deemed treatment-related, and no evidence of endometrial hyperplasia, malignancy, or liver toxicity.

Potential Role of Elinzanetant

The authors suggest that elinzanetant may be a useful option for women who cannot or prefer not to use hormone therapy, including those with a history of estrogen-sensitive cancers, venous thromboembolism, or migraines with aura. The dual targeting of the NK-1 and NK-3 receptors by elinzanetant, in contrast to the NK-3 receptor-specific fezolinetant, may contribute to the broader improvements observed in vasomotor symptoms, sleep, and quality of life.

Key Points

1. The research paper summarizes the findings from three randomized controlled trials (OASIS 1, 2, and 3) evaluating the efficacy and safety of the investigational drug elinzanetant for the treatment of vasomotor symptoms associated with menopause.

2. Elinzanetant is a selective neurokinin receptor antagonist that targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons, which are thought to play a role in thermoregulation and hot flashes during menopause. The OASIS 1 and 2 trials enrolled postmenopausal women aged 40-65 years with at least 50 moderate to severe vasomotor symptoms per week, and randomized them to receive either 120 mg of oral elinzanetant or placebo once daily for 12 weeks, after which the placebo group switched to elinzanetant for the final 14 weeks.

3. The results showed that elinzanetant led to a significant reduction in the daily frequency and severity of vasomotor symptoms compared to placebo. Elinzanetant also significantly improved sleep disturbance and quality of life measures. The OASIS 3 trial, which assessed elinzanetant for 1 year, supported the findings from the earlier trials, demonstrating sustained efficacy over a longer duration.

4. Regarding safety, the most commonly reported adverse events with elinzanetant were headache, fatigue, and sleepiness. A higher proportion of elinzanetant users discontinued the study compared to placebo. However, there were no serious adverse events deemed treatment-related, and no evidence of endometrial hyperplasia, malignancy, or liver toxicity.

5. The authors suggest that elinzanetant may be a useful option for women who cannot or prefer not to use hormone therapy, including those with a history of estrogen-sensitive cancers, venous thromboembolism, or migraines with aura.

6. The dual targeting of the NK-1 and NK-3 receptors by elinzanetant, in contrast to the NK-3 receptor-specific fezolinetant, may contribute to the broader improvements observed in vasomotor symptoms, sleep, and quality of life.

Reference –

Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA. Published online August 22, 2024. doi:10.1001/jama.2024.14618

Copenhagen: New data shows that the number of children suffering a seizure after swallowing medications or illegal substances has doubled between 2009 and 2023 in the US.

The findings were presented today (Wednesday) at the European Emergency Medicine Congress.

The most common substances involved in these poisonings include over-the-counter antihistamines, prescription antidepressants and painkillers, and illegal synthetic cannabinoids.

Dr Conner McDonald from the University of Virginia School of Medicine told the Congress: “Seizure is one of the most severe symptoms a poisoned patient can experience, and children are particularly vulnerable. Depending on variables such as where a seizure happens, how long it continues and the pre-existing health of the child, seizures can lead to long-term damage or even death.”

Working with Professor Christopher Holstege, Chief of the Division of Medical Toxicology at the University of Virginia School of Medicine, and colleagues, Dr Farah gathered data from the US National Poison Data System on seizures in children and teenagers (under the age of 20 years) that resulted from exposure to any single substance between 1 January 2009 and 31 December 2023.

The National Poison Data System brings together information from the 55 poison centres across the US. These centres are consulted in the most serious cases of poisoning, including poisoning in children that results in seizure.

The researchers analysed the data according to the children’s ages and the substance they had consumed. Overall, they found that cases had increased from 1,418 in 2009 to 2,749 in 2023, corresponding with an average yearly increase of five per cent.

Among children aged between six and 19 years, the number of cases had doubled over the 15-year period. In children under six years, there was a 45% increase in cases over the 15-year period.

The substances responsible for most of this increase include diphenhydramine (an over-the-counter antihistamine commonly used for allergies, hay fever and nasal congestions), tramadol (an opioid prescribed for pain in adults), bupropion (an antidepressant prescribed for adults and children), and synthetic cannabinoids known as K2 or spice (illegal substances that are man-made and chemically similar to substances found in the cannabis plant).

Dr McDonald explained: “Diphenhydramine can be purchased in the United States in bottles containing 500 or 600 tablets. Bupropion is being more frequently prescribed to treat depression in adults and children. Other legal and illegal drugs can be bought online and shipped around the world. Therefore, these drugs are becoming more available in homes and within the reach of children.”

Speaking before the Congress, Professor Holstege said: “The increase in seizures in children exposed to these drugs is extremely worrying and must be addressed. It’s a stark reminder to parents and carers to store medications safely so that children cannot get hold of them.

“In the US, we also need to have a serious discussion on whether products like diphenhydramine should be sold in containers with such large quantities of pills and whether these products should be contained within blister packs to make it more difficult for children and suicidal individuals to gain access to such a large quantity.”

Dr Barbra Backus is chair of the EUSEM abstract selection committee. She is an emergency physician in Rotterdam, The Netherlands, and was not involved with the research. She said: “The increase in drug poisoning among children is worrysome. Although these data are for the US, we know that drugs are the most common sources of poisoning in children around the world. It is important that we keep looking for safer distribution and storage of medication. Blister packs and child-resistant pill bottles can help, but all drugs, whether they are over the counter, prescribed, or illegal should be kept out of reach or locked away where children cannot access them.

“No parent or carer ever wants to see their child suffer a drug-induced seizure, especially when it could have been prevented.”

Seizures caused by children swallowing medications or illegal substances doubled over 15-year period European Emergency Medicine Congress (EUSEM 2024)

Airway blockage poses a critical emergency and poses substantial challenges for healthcare providers, as effectively managing this condition requires precise decision-making. Numerous patients with airway obstruction necessitate interventions beyond the confines of the operating room, each carrying distinct risks. Recent paper investigated factors associated with emergency interventions in acute airway obstructive diseases (AAODs) in internal medicine conditions. The study was a retrospective observational single-center study that included 150 patients admitted to Yokosuka Kyosai Hospital, Japan, for AAOD between April 2012 and March 2022. The study aimed to identify predictors for emergency interventions such as intubation, cricothyroidotomy, and tracheostomy in patients with AAODs.

Results revealed several significant findings from univariate analysis, including age, Glasgow Coma Scale, respiratory rate, National Early Warning Score (NEWS), Sequential Organ Failure Assessment (SOFA) score, stridor, dysphagia, drooling, frequent suctions, airway examination abnormalities (AEAs), and diagnosis. Multivariate logistic regression indicated that AEA, upper airway diseases, and SOFA score were predictors for intervention, with AEA being associated with the highest risk for airway interventions. However, the study found that the sensitivity and specificity of AEA were insufficient.

Diseases and Predictive Factors

The paper also discussed various diseases that can lead to airway emergencies, such as acute epiglottitis, peritonsillar abscess, tonsillitis, pharyngitis, Lemierre’s syndrome, hemoptysis, and airway foreign body. It highlighted the importance of thorough physical examinations in predicting airway interventions and the need for accurate diagnostic methods in emergency settings.

Limitations and Further Research

The authors mentioned the limitations of the study, including its retrospective nature and the need for a multicenter study to confirm the results. They also discussed the importance of physical examinations in predicting airway interventions and the need for future prospective studies to overcome the study’s limitations.

Conclusion

In conclusion, the paper identified AEA, upper airway diseases, and SOFA score as predictors for emergency interventions in AAOD. However, it highlighted the limitations of these predictors and the need for further research to improve the accuracy of predicting interventions for AAOD.

Key Points

– The study investigated factors associated with emergency interventions in acute airway obstructive diseases (AAODs) in internal medicine conditions.

– It was a retrospective observational single-center study involving 150 patients admitted to Yokosuka Kyosai Hospital, Japan, for AAOD between April 2012 and March 2022.

– The study aimed to identify predictors for emergency interventions such as intubation, cricothyroidotomy, and tracheostomy in patients with AAODs.

– Factors associated with emergency interventions included age, Glasgow Coma Scale, respiratory rate, National Early Warning Score (NEWS), Sequential Organ Failure Assessment (SOFA) score, stridor, dysphagia, drooling, frequent suctions, airway examination abnormalities (AEAs), and diagnosis.

– AEA, upper airway diseases, and SOFA score were identified as predictors for intervention, with AEA being associated with the highest risk for airway interventions, but with insufficient sensitivity and specificity.

– Diseases such as acute epiglottitis, peritonsillar abscess, tonsillitis, pharyngitis, Lemierre’s syndrome, hemoptysis, and airway foreign body were discussed as conditions leading to airway emergencies, emphasizing the importance of thorough physical examinations and the need for accurate diagnostic methods in emergency settings.

Reference –

Suzuki N, Doi T, Abe T, et al. (October 07, 2024) Predictors of Emergency Interventions in Acute Airway Obstructive Diseases: A Retrospective Single-Center Observational Study. Cureus 16(10): e71031. DOI 10.7759/cureus.71031

People with constipation may have a higher risk of having a heart attack or stroke, and the risk increases in people who also have high blood pressure. The findings of a new study are published in the American Journal of Physiology-Heart and Circulatory Physiology. The study has been chosen as an APSselect article for October.

High blood pressure, diabetes, obesity, smoking and age are a few of the traditional risk factors for cardiovascular disease. A recent study of the connections between the heart and gut revealed that constipation-a condition that also increases with age-is associated with high blood pressure and cardiovascular disease. This heart and gut connection was independent of these traditional risk factors or medication used to treat high blood pressure such as calcium channel blockers.

In this study, the research team used data from over 400,000 people in the U.K. Biobank to determine if constipation could be an independent, nontraditional risk factor for cardiovascular disease. This database contains electronic medical records, lifestyle surveys, and self-reported health conditions and medication use data. Because the biobank contained limited information from nonwhite populations at the time of data collection, the current study is based on data from males and females of white European ancestry.

The researchers found 11.5% of people analyzed had experienced at least one major adverse cardiac event, with much higher rates in men (67.3% of all cases who had a cardiovascular event). Constipation rates overall were higher in women (55.9% of all cases).

More than 157,400 of the participants had high blood pressure and 8.6% of them were also diagnosed with constipation. Those with constipation “demonstrated a significantly increased risk of [major adverse cardiac events] compared with those with regular bowel habits,” the researchers wrote. This increased risk was adjusted for the use of constipating medications.

In addition, the researchers found genetic correlations in more than 9 million instances of genetic variations between constipation and major cardiac events, showing constipation shares 21% to 27% of genetic variants with cardiovascular disease. Genome analysis estimated constipation to be a heritable trait about 4% of the time.

Identifying the associations between constipation and heart disease can help scientists “discover new therapeutic interventions and implement more effective management strategies based on individual risk assessment in line with precision medicine principles,” the researchers wrote.

Reference:

Tenghao Zheng,Leticia Camargo Tavares,Mauro D’Amato, andFrancine Z. Marques, Constipation is associated with an increased risk of major adverse cardiac events in a UK population, American Journal of Physiology-Heart and Circulatory Physiology, https://doi.org/10.1152/ajpheart.00519.2024