Use of benzodiazepines for seizure control in kids tied to future risk of polytherapy, reveals study

Managing antiseizure treatment in epileptic patients relies on the benefit–risk ratio. More data on using antiseizure medication (ASM) in children must be available.

The present study published in Epilepsia investigated the prevalence of prescription patterns for antiseizure medication for pediatric epilepsy patients in France. The most common antiseizure medicine prescribed was valproate, followed by lamotrigine and levetiracetam. From 2013-2016, there was reduced prevalence of benzodiazepine usage, whereas the prevalence of levetiracetam use increased. Using benzodiazepines increased the likelihood of switching from bitherapy to polytherapy. The usage of benzodiazepines may pose a future risk for polytherapy prescriptions; they highlight
This study described antiseizure medication use in children with epilepsy (CwE) in France, focusing on chronic use of benzodiazepines and related implications.
Researchers conducted a 5-year cohort study from January 2012. They used data from the French national health care data system Children with Epilepsy were identified through the International Classification of Diseases, 10th Revision codes and medications( January 2012 to December 2015; followed them until December 2016) . They described ASMs and assessed whether the risk of initiating a polytherapy after a bitherapy depends on whether benzodiazepine was included in the bitherapy.
Key findings from this study are:
Researchers identified 62 885 Children with Epilepsy.
Valproate was the most reimbursed ASM (40%).
This was followed by lamotrigine, levetiracetam, clobazam, and carbamazepine, which constituted 17.6%, 9.3%, 6.1 %, and 5.8 %, respectively.
Prescriptions were initiated in 74.5% of Children with epilepsy at the hospital.
The number of CwE with at least one benzodiazepine reimbursement decreased from 15.3% to 10.1 % in 2013 and 2016, respectively.
CwE prevalencewith levetiracetam reimbursements increased. On the other hand, the prevalence with valproate decreased.
A switch from a bitherapy to a polytherapy was more likely when the bitherapy included a benzodiazepine with a subdistribution hazard ratio or sHR of 1.20
They concluded that during the study period, CwE prevalence with at least one benzodiazepine reimbursement decreased. Benzodiazepines were also associated with increased use of subsequent ASM polytherapy.
Reference:
Auvin, S., Guillo, S., De Rycke, Y., Tran, D., & Tubach, F. (2024). Benzodiazepines for pediatric epilepsies and their risks in a cohort within the French health care data. Epilepsia. https://doi.org/10.1111/epi.17906

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Which is better – intravenous or nebulized dexmedetomidine as premedication?

Recently published research paper investigates the comparative effectiveness of nebulized dexmedetomidine versus traditional intravenous administration in attenuating hemodynamic responses associated with laryngoscopy and tracheal intubation. The study involved 60 patients undergoing surgery under general anesthesia, who were randomly allocated into two groups receiving either intravenous or nebulized dexmedetomidine as premedication. The study found that nebulized dexmedetomidine resulted in better obtundation of hemodynamic responses following laryngoscopy and maintained hemodynamics intraoperatively, compared to intravenous administration. Nebulized dexmedetomidine was associated with a lower sedation score and fewer adverse effects, such as bradycardia and hypotension, compared to intravenous administration. The study highlights the potential benefits of alternative administration methods for dexmedetomidine in improving perioperative outcomes and enhancing patient safety. The findings suggest that nebulized dexmedetomidine may offer a promising alternative to intravenous administration for attenuating hemodynamic responses during airway manipulation. The study also discusses the importance of assessing the mode of dexmedetomidine delivery on hemodynamic responses and emphasizes the need for further exploration and research in diverse clinical settings and patient populations.

Comparison of Administration Groups

The comparison of basic parameters between the two administration groups showed no significant differences in age, weight, or comorbidities, indicating that the randomization process was effective in creating homogeneous groups. The study also found no significant difference in the ASA grades between the groups. The comparison of baseline vitals showed no significant differences in heart rate, systolic and diastolic blood pressure, MAP, respiratory rate, and temperature between the groups. The study observed a statistically significant decrease in heart rate, blood pressure, and MAP in the intravenous group compared to the nebulized group at various time intervals after induction, highlighting the importance of vigilant monitoring during the post-induction period. Additionally, the study found that nebulized dexmedetomidine achieved a deeper level of sedation compared to intravenous administration.

Study Limitations and Conclusion

The research paper also discusses limitations, such as the evaluation of a single dose of dexmedetomidine and the exclusion of other routes of administration, suggesting the need for further research. Overall, the study presents valuable insights into the potential benefits of nebulized dexmedetomidine in achieving optimal sedation, minimizing hemodynamic fluctuations, and improving patient safety during perioperative care.

Reference –

Singla A, Saraswat R K, Bharadwaj A, et al. (February 23, 2024) Nebulized Versus Intravenously Administered Dexmedetomidine for Obtunding

Hemodynamic Responses to Laryngoscopy and Tracheal Intubation: A Randomized Double-Blind Comparative Study. Cureus 16(2): e54768. DOI

10.7759/cureus.54768

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Water-Free Cyclosporine Solution may Improve Dry Eye Disease symptoms: JAMA

A recent study published in the recent edition of Journal of American Medical Association revealed promising results in the treatment of Dry Eye Disease (DED). This study focused was set out to evaluate the efficacy and safety of a water-free cyclosporine ophthalmic solution in Chinese participants with moderate to severe DED.

The multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial was conducted from March 4, 2021 to July 22, 2022 and enrolled a total of 206 adult participants from 12 hospitals in China. The participants were randomly assigned to receive either the water-free cyclosporine solution or a vehicle control. After a 29-day treatment period, the results were analyzed.

The primary endpoints of the study were changes in total corneal fluorescein staining (tCFS) and dryness score on a visual analog scale (VAS) at day 29. The findings revealed a marked improvement in tCFS in the cyclosporine group when compared to the vehicle group by demonstrating the superiority of the treatment. However, the dryness score on the VAS did not show notable improvement between the two groups at day 29.

The study also evaluated the safety profile of the treatment. During the 29-day treatment period, treatment-related adverse events were reported in a small percentage of participants in both the cyclosporine and vehicle groups that indicates an acceptable safety profile for the water-free cyclosporine solution. Overall, the development of a water-free cyclosporine ophthalmic solution presents a potential solution to the challenges posed by the hydrophobic nature of traditional cyclosporine formulations in delivering effective treatment to the ocular surface.

Reference:

Peng, R., Jie, Y., Long, Q., Gong, L., Zhu, L., Zhong, X., Zhao, S., Yan, X., Gu, H., Wu, H., Li, G., Zhang, K., Krösser, S., Xu, R., & Hong, J. (2024). Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease. In JAMA Ophthalmology. American Medical Association (AMA). https://doi.org/10.1001/jamaophthalmol.2024.0101

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Exercise Caution: Meta-analysis reports significant prevalence of bleeding after PCI

Iran: A systematic review and meta-analysis has shown that the incidence of bleeding after PCI is 4.4 %, which is a significant result. The findings, published in the Indian Heart Journal, highlight the need for healthcare policymakers to pay more attention to the complications associated with PCI.

The researchers suggest that interventional cardiologists should consider the effective factors in these bleeding and how to control and treat them due to the importance of this complication.

Percutaneous coronary intervention (PCI) is one of the most widely used methods for treating coronary artery disease. Previous studies have shown that complications such as hematoma, bleeding, and embolism may occur due to the trauma inflicted on the vessels during the procedure. Among these complications, the most common one of PCI is bleeding, which is tied to an increased risk of adverse events, including myocardial infarction (MI), death, and stroke, and an increased length of hospital costs and stay.

Reza Heidary Moghadam, Kermanshah University of Medical Sciences, Kermanshah, Iran, and colleagues aimed to determine the prevalence of bleeding after PCI through a systematic review and meta-analysis covering the period from 1989 to 2023.

Multiple databases were searched using validated keywords. The I2 index was used to check for heterogeneity among studies. The meta-analysis included observational studies (case-control studies, cohort studies, cross-sectional studies), access to the full text of the article, randomized clinical trials, and studies that reported the frequency or percentage of bleeding after PCI.

Based on the analysis, the researchers reported the following findings:

  • The review of 8 studies, with a sample size of 397,298 participants, showed high heterogeneity (I2: 97.8 %). Therefore, the random effects method was used to analyze the results.
  • The prevalence of bleeding after intervention in percutaneous coronary arteries was reported to be 4.4 %.

In conclusion, the incidence of bleeding after PCI was reported to be 4.4 %, which is a significant result. Therefore, the results can serve as an important criterion for developing suitable treatment and prevention strategies.

“Health policymakers can also utilize the findings of the meta-analysis to prioritize research on the complication of bleeding after PCI and its outcomes and implement effective measures to prevent and manage this complication.,” the researchers wrote.

One limitation of the meta-analysis is that it only included studies published in English, potentially excluding relevant studies published in other languages. Furthermore, various studies were excluded due to inadequate quality, such as those that did not report prevalence and those with small sample sizes.

Reference:

Heidary Moghadam R, Mohammadi A, Salari N, Ahmed A, Shohaimi S, Mohammadi M. The prevalence of bleeding after percutaneous coronary interventions: A systematic review and meta-analysis. Indian Heart J. 2024 Jan-Feb;76(1):16-21. doi: 10.1016/j.ihj.2024.01.009. Epub 2024 Jan 10. PMID: 38216122.

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High CRP in Metabolic Syndrome patients Linked to high Cancer Risk, finds study

Metabolic syndrome (MetS) has long been associated with an increased risk of cancer development. However, the dynamics of MetS over time and its correlation with cancer risk remain understudied. This study delves into the trajectories of MetS scores and their relationship with the onset of various cancers, shedding light on the importance of sustained monitoring for early intervention. This study was published in the journal Cancer by Deng L. and colleagues,

Metabolic syndrome, characterised by a cluster of metabolic abnormalities including obesity, hypertension, dyslipidemia, and insulin resistance, has been linked to heightened cancer susceptibility. Chronic inflammation, often coexisting with MetS, further exacerbates this risk, potentially accelerating cancer initiation and progression.

In this prospective cohort study, researchers analysed data from 44,115 participants to investigate the association between MetS score trajectories and new-onset cancer. Latent mixture modelling was employed to identify distinct MetS score trajectory patterns, and Cox proportional hazards regression models were used to assess cancer risk based on these patterns.

Key Findings:

Four MetS score trajectory patterns were identified:

  • Low-stable (n = 4657)

  • Moderate-low (n = 18,018)

  • Moderate-high (n = 18,288)

  • Elevated-increasing (n = 3152)

Compared to those with a low-stable trajectory, individuals with an elevated-increasing pattern had a significantly higher risk of overall cancer incidence and specific cancer types:

  • Overall cancer risk (HR: 1.27; 95% CI: 1.04–1.55)

  • Breast cancer (HR: 2.11; 95% CI: 1.04–4.34)

  • Endometrial cancer (HR: 3.33; 95% CI: 1.16–6.77)

  • Kidney cancer (HR: 4.52; 95% CI: 1.17–10.48)

  • Colorectal cancer (HR: 2.54; 95% CI: 1.27–5.09)

  • Liver cancer (HR: 1.61; 95% CI: 1.09–4.57)

  • Moreover, among participants exhibiting chronic inflammation (C-reactive protein levels ≥3 mg/L), the elevated-increasing trajectory was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers.

The research  indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer.

Furthermore the. study underscores the significance of long-term monitoring and evaluation of MetS trajectories in assessing cancer risk. Identification of elevated-increasing MetS trajectories may serve as an early indicator for heightened cancer susceptibility, particularly for breast, endometrial, kidney, colorectal, and liver cancers. This emphasises the necessity for proactive management strategies targeting MetS to mitigate cancer risk effectively.

Reference:

Deng, L., Liu, T., Liu, C.-A., Zhang, Q., Song, M.-M., Lin, S.-Q., Wang, Y.-M., Zhang, Q.-S., & Shi, H.-P. The association of metabolic syndrome scores trajectory patterns with risk of all cancer types. Cancer,2024. https://doi.org/10.1002/cncr.35235

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Elevated CSF glial fibrillary acid protein linked to nonrelapsing progressive multiple sclerosis: JAMA

USA: A recent cohort study published in JAMA Neurology has shed light on the emerging cerebrospinal fluid (CSF) biomarkers of disease activity and progression in multiple sclerosis.

In the study, activated glial markers (glial fibrillary acid protein [GFAP] in particular) and neurofilament heavy chains were associated specifically with nonrelapsing progressive disease outcomes. Elevated CSF GFAP was associated with long-term multiple sclerosis disease progression.

“We found that elevated GFAP and neurofilament heavy chain were associated with nonrelapsing progression and lymphocyte measures were associated with relapsing biology in patients with both relapsing and primary progressive clinical phenotypes,” the researchers wrote. “Elevated neurofilament light chain reflected both processes.”

There is a lack of biomarkers distinguishing nonrelapsing progressive disease biology from relapsing biology in multiple sclerosis. Cerebrospinal fluid is an accessible fluid that most closely reflects central nervous system biology. Considering this, Anne H. Cross, Washington University School of Medicine, St Louis, Missouri, and colleagues aimed to identify CSF biological measures associated with progressive MS pathobiology.

For this purpose, the researchers assessed data from two prospective MS cohorts: a test cohort provided serial CSF, clinical, and imaging assessments in a multicenter study of patients with relapsing MS (RMS) or primary progressive MS (PPMS) who were initiating anti-CD20 treatment. A single-site confirmation cohort assessed CSF at baseline and long-term (>10 years) clinical follow-up (analysis: 2022-2023).

Test-cohort participants were initiated standard-of-care ocrelizumab treatment. Confirmation-cohort participants received standard-of-care disease-modifying MS therapies or were untreated.

The study’s outcomes were twenty-five CSF markers, including neurofilament heavy chain, neurofilament light chain, and GFAP; 24-week confirmed disability progression (CDP24); and brain magnetic resonance imaging measures reflecting tissue loss, focal injury, and progressive biology (slowly expanding lesions [SELs]).

The following were the key findings of the study:

  • The test cohort (n = 131) included 100 patients with RMS (mean age, 36.6 years; Expanded Disability Status Scale [EDSS] score, 0-5.5), and 31 patients with PPMS (mean age, 44.9 years; EDSS score, 3.0-6.5).
  • The confirmation cohort (n = 68) included 41 patients with RMS and 27 with PPMS enrolled at diagnosis (age 40 years).
  • In the test cohort, GFAP was correlated with SEL count (r = 0.33), a greater proportion of T2 lesion volume from SELs (r = 0.24), and lower T1-weighted intensity within SELs (r = –0.33) but not with acute inflammatory measures.
  • Neurofilament heavy chain was correlated with SEL count (r = 0.25) and lower T1-weighted intensity within SELs (r = –0.28).
  • Immune markers correlated with measures of acute inflammation and, unlike GFAP, were impacted by anti-CD20.
  • In the confirmation cohort, higher baseline CSF GFAP levels were associated with long-term CDP24 (hazard ratio, 2.1).

“The findings underscore a role for chronic inflammation and glial activity in nonrelapsing progressive pathobiology and identify GFAP and NfH as more specific candidate biomarkers for progressive biology, potentially improving on NfL, which indicates both injury from acute disease activity and insidious injury,” the research team wrote.

“Future clinical trials should incorporate combined measurement of these markers, which could be useful for assessing the effect of emerging therapies on subclinical relapsing and progressive disease mechanisms,” they concluded.

Reference:

Cross AH, Gelfand JM, Thebault S, et al. Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis. JAMA Neurol. Published online March 11, 2024. doi:10.1001/jamaneurol.2024.0017

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Magnolia berry, fruit used in Chinese medicine, promising as treatment in colon cancer: Study

UK: A new study published in ACS Pharmacology & Translational Science found that a fruit used in Chinese medicine contains a very effective compound that could help treat colon cancer.

The compound called Schisandrin B (Sch B), a lignan extracted from the fruit of Schisandra chinensis (known as five-flavor berry or magnolia berry), induced apoptosis and inhibited cell proliferation and tumor growth in vitro and in vivo. The findings provide an essential background for clinical trials investigating the effects of Sch B in patients with colon cancer.

The anti-tumor compound, when introduced to late-stage colon cancer cells, performed especially well.

The tiny magnolia berry, a staple in traditional Chinese medicine, may hold the key to fighting one of the most common and lethal forms of cancer. The plant is already widely available online, though it should be taken only under medical supervision due to various known adverse drug interactions.

Colon cancer, or colorectal cancer, is among the most prevalent and lethal malignant tumors in the world. The lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B is a lignan extracted from the fruit of Schisandra chinensis and has been reported for its anticancer properties. However, to date, no studies have been performed to characterize the exact molecular mechanisms underlying the antitumorigenic effects of Sch B in colon cancer.

To address the knowledge gap, Murphy Lam Yim Wan, School of Pharmacy and Biomedical Sciences, Faculty of Science and Health, University of Portsmouth, Portsmouth, United Kingdom, and colleagues aimed to explore the antitumorigenic effects of Sch B in colon cancer and to understand the underlying therapeutic mechanism.

For this purpose, the researchers performed a comprehensive analysis of the molecular mechanism underlying the antitumorigenic effects of Sch B on human colon cancer cells using a combination of RNA-seq, Raman spectroscopy, molecular biological experiments, and computational docking.

The in vivo efficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines.

The key findings of the study were as follows:

  • Raman spectroscopy, computational, RNA-seq, and molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis.
  • CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis.
  • Sch B reduced colon tumor growth in vivo.

The latest study gives cause for hope as it opens up new avenues toward more targeted, less toxic therapies where natural compounds play a larger role in cancer treatment.

Despite the promising potential of Sch B and magnolia berry extract in cancer treatment, the high costs of clinical trials and the inability to patent natural products pose significant barriers to their approval as medical treatments.

“These results provided an essential background for clinical trials examining the effects of Sch B in colon cancer patients,” the researchers concluded.

Reference:

ACS Pharmacol. Transl. Sci. 2024, 7, 3, 863–877. Publication Date: February 22, 2024. https://doi.org/10.1021/acsptsci.4c00009

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Proinflammatory diet, higher habitual salt intake tied to increased risk of type 2 diabetes: Study

China: Adopting an anti-inflammatory diet and reducing salt intake can significantly reduce the risk of type 2 diabetes (T2D), a recent study has shown.

The findings published in Diabetes, Obesity and Metabolism journal emphasize the importance of promoting healthy eating habits and reducing high-salt foods intake to prevent T2D and improve public health.

“Participants who followed a proinflammatory diet had an 18% higher risk of type 2 diabetes than those who adhered to an anti-inflammatory diet, after accounting for all confounding factors,” the researchers reported.

In the fully adjusted model, participants who reported always adding salt to foods had a higher T2D (HR, 1.30) risk than those who never or rarely added salt.

The study was conducted by Ningjian Wang, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues to explore the relationship between proinflammatory diet, habitual salt intake and the onset of type 2 diabetes.

For this purpose, the researchers conducted a prospective study among 171 094 UK Biobank participants who completed at least one 24-hour dietary questionnaire and were free of diabetes at baseline. The participants were followed up until March 1, 2023, for T2D incidence, with diagnosis information obtained from linked medical records.

Based on 28 food parameters, an Energy-adjusted Diet Inflammatory Index (E-DII) was calculated. Habitual salt intake was determined through the self-reported frequency of salt addition to foods. The Cox proportional hazard regression model was used to test the associations between E-DII, habitual salt intake, and type 2 diabetes incidence.

The study led to the following findings:

  • Over a median follow-up period of 13.5 years, 6216 cases of type 2 diabetes were documented.
  • Compared with participants with a low E-DII (indicative of an anti-inflammatory diet), participants with a high E-DII (indicative of a pro-inflammatory diet) had an 18% heightened risk of developing type 2 diabetes.
  • The association between E-DII and type 2 diabetes tends to be linear after adjustment for major confounders.
  • Participants with a proinflammatory diet and always adding salt to foods had the highest risk of type 2 diabetes incidence (hazard ratio 1.60).

In conclusion, the findings indicate that a higher habitual salt intake and proinflammatory diet were associated with an increased risk of type 2 diabetes.

“These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes,” the researchers concluded.

Reference:

Shen W, Cai L, Wang B, Li J, Sun Y, Chen Y, Xia F, Wang N, Lu Y. Associations of a proinflammatory diet, habitual salt intake, and the onset of type 2 diabetes: A prospective cohort study from the UK Biobank. Diabetes Obes Metab. 2024 Feb 26. doi: 10.1111/dom.15517. Epub ahead of print. PMID: 38409502.

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MSR 2023: Now possible to open medical college with intake capacity of only 50 MBBS seats

It is now possible to open a medical college with an intake capacity of only 50 MBBS seats under the new Minimum Standard Requirements (MSR) 2023 regulations for undergraduate medical courses.

“These new rules enable even smaller hospitals with a 220-bed capacity to start a medical college for 50 MBBS students,” the National Medical Commission (NMC) officials told the Medical Dialogues team.

For more information click on the link

 

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Vaccine monitoring is crucial as SARS-CoV-2 variants continue to evolve, says study

Researchers at the Francis Crick Institute and the National Institute for Health and Care Research Biomedical Research Centre at UCLH have highlighted the importance of continued surveillance of emerging SARS-CoV-2 variants and vaccine performance as the virus continues to evolve.

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