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HPA axis function in patients with right and left focal lateralized epilepsy

Neuro Endocrinol Lett. 2024 Apr 7;45(2). Online ahead of print.

ABSTRACT

OBJECTIVES: There is a complex, reciprocal link between epilepsy and the hypothalami pituitary-adrenal (HPA) axis. This study aimed to evaluate the role of the HPA axis in individuals with focal epilepsy, including those with right- or left-hemispheric lateralized epilepsy.

MATERIAL AND METHODS: The study comprised 60 individuals with focal epilepsy, ages 18 to 85, with seizures coming from a single hemisphere, no destructive lesions on cranial magnetic resonance imaging, and 32 healthy persons. Blood was drawn from the patient and control groups at 8.00 for serum cortisol level and at 23.00 for serum melatonin level. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were administered to both the patient and control groups.

RESULTS: Patients showed decreased melatonin levels (p < 0.001) and poorer sleep quality (p = 0.035). The cortisol level of the patients was found to be lower than the cortisol level of healthy individuals, although it was not statistically significant (p = 0.107). Cortisol and melatonin levels did not significantly differ between patients with seizures coming from the right or left hemisphere. The patients with seizures originating from the left hemisphere had a longer duration of epilepsy disease (p = 0.013), higher seizure frequency (p = 0.013), lower age of first seizure onset (p = 0.038), and a higher rate of polytherapy (p = 0.05).

CONCLUSION: Low cortisol and melatonin levels in patients with focal epilepsy may be an indicator of disruption in the HPA axis. There is no significant difference in the HPA axis function between patients with focal epilepsy according to the epileptic hemisphere.

PMID:38583190

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CD14 Polymorphism Is Not Associated with SARS-CoV-2 Infection in Central European Population

Folia Biol (Praha). 2023;69(5-6):181-185. doi: 10.14712/fb2023069050181.

ABSTRACT

A 2021 in silico study highlighted an association between the CD14 polymorphism rs2569190 and increased susceptibility to SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19). The aim of our study was to confirm this finding. We analysed the CD14 polymorphism (C→T; rs2569190) in 516 individuals who tested positive for SARS-CoV-2, with differing disease severity (164 asymptomatic, 245 symptomatic, and 107 hospitalized). We then compared these patients with a sample from the general population consisting of 3,037 individuals using a case-control study design. In comparison with carriers of the C allele, TT homozygotes accounted for 21.7 % of controls and 20.5 % in SARS-CoV-2-positive individuals (P = 0.48; OR; 95 % CI – 0.92; 0.73-1.16). No significant differences in the distribution of genotypes were found when considering co-dominant and recessive genetic models or various between-group comparisons. The CD14 polymorphism is unlikely to be an important predictor of COVID-19 in the Caucasian population in Central Europe.

PMID:38583179 | DOI:10.14712/fb2023069050181

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Does Mixing Activated Charcoal With Cola Improve Tolerability Without Affecting Pharmacokinetics? A Randomized Controlled Crossover Trial

J Emerg Nurs. 2024 Apr 6:S0099-1767(24)00077-1. doi: 10.1016/j.jen.2024.03.001. Online ahead of print.

ABSTRACT

INTRODUCTION: Activated charcoal is the most common form of gastrointestinal decontamination used for the poisoned patient. One limitation to its use is patient tolerability due to palatability. Some recommend mixing activated charcoal with cola to improve palatability. An important question is whether mixing activated charcoal with cola affects the ability of the activated charcoal to adsorb xenobiotic.

METHODS: This was a prospective randomized controlled crossover trial. Five healthy adults aged 18 to 40 years were recruited. Participants received 45 mg/kg acetaminophen rounded down to the nearest whole tablet. One hour later, they were randomized to receive 50 g of an activated charcoal-water premixture alone or mixed with cola. Acetaminophen levels were collected. The area under the curve of acetaminophen concentrations over time was measured as a marker for degree of absorption. Participants also completed an appeal questionnaire in which they rated the activated charcoal preparations. Participants would then return after at least 7 days to repeat the study with the other activated charcoal preparation.

RESULTS: Four male participants and 1 female participant were recruited. There was no statistical difference in preference score for activated charcoal alone versus the cola-activated charcoal mixture. There was no statistical difference in the area under the curve of acetaminophen concentrations over time between activated charcoal alone and the cola-activated charcoal mixture. Of note, the study is limited by the small sample size, limiting its statistical power.

DISCUSSION: The absorption of acetaminophen in an overdose model is no different when participants received activated charcoal alone or a cola-activated charcoal mixture as suggested by area under the curve. In this small study, there was no difference in preference for activated charcoal alone or a cola-activated charcoal mixture across a range of palatability questions. On an individual level, some participants preferred the activated charcoal-cola mixture, and some preferred the activated charcoal alone.

PMID:38583171 | DOI:10.1016/j.jen.2024.03.001

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Near-infrared fluorescence lymph node template region dissection plus backup lymphadenectomy in open radical cystectomy for bladder cancer using an innovative handheld device: A single center experience

J Surg Oncol. 2024 Apr 7. doi: 10.1002/jso.27618. Online ahead of print.

ABSTRACT

BACKGROUND: The extent of pelvic lymphadenectomy (PLND) as part of radical cystectomy (RC) for bladder cancer (BC) remains unclear. Sentinel-based and lymphangiographic approaches could lead to reduced morbidity without sacrificing oncologic safety.

OBJECTIVE: To evaluate the feasibility and diagnostic value of fluorescence-guided template sentinel region dissection (FTD) using a handheld near-infrared fluorescence (NIRF) camera in open radical cystectomy.

DESIGN, SETTING, AND PARTICIPANTS: After peritumoral cystoscopic injection of indocyanine green (ICG) 21 patients underwent open RC with FTD due to BC between June 2019 and June 2021. Intraoperatively, the FIS-00 Hamamatsu Photonics® NIRF camera was used to identify and resect fluorescent template sentinel regions (FTRs) followed by extended pelvic lymphadenectomy (ePLND) as oncological back-up.

OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Descriptive analysis of positive and negative results per template region.

RESULTS AND LIMITATIONS: FTRs were identified in all 21 cases. Median time (range) from ICG injection to fluorescence detection was 75 (55-125) minutes. On average (SD), 33.4 (9.6) lymph nodes were dissected per patient. Considering template regions as the basis of analysis, 67 (38.3%) of 175 resected regions were NIRF-positive, with 13 (7.4%) regions harboring lymph node metastases. We found no metastatic lymph nodes in NIRF-negative template regions. Outside the standard template, two NIRF-positive benign nodes were identified.

CONCLUSION: The concept of NIRF-guided FTD proved for this group all lymph node metastases to be found in NIRF-positive template regions. Pending validation in a larger collective, resection of approximately 40% of standard regions may be sufficient and may result in less morbidity.

PMID:38583145 | DOI:10.1002/jso.27618

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Massed written exposure therapy delivered to veterans with posttraumatic stress symptoms on an acute inpatient mental health unit

J Trauma Stress. 2024 Apr 7. doi: 10.1002/jts.23042. Online ahead of print.

ABSTRACT

Written exposure therapy (WET) is a brief, manualized trauma-focused treatment typically delivered in five individual weekly sessions. Given the brevity and effectiveness of WET, researchers have begun to focus on its delivery in a massed format. However, only one case study examining massed delivery has been published to date. As such, the objective of the current study was to examine the acceptability, feasibility, and preliminary effectiveness of massed WET among veterans with a trauma- and stressor-related disorder receiving care on an acute inpatient mental health unit. Veterans (N = 26) were assessed prior to, immediately after, and 1 month following massed WET. Most veterans found massed WET to be useful and acceptable. Recruitment and retention rates suggested that the treatment was feasible. Notably, the results revealed statistically significant reductions in overall posttraumatic stress symptoms, ηp 2 = .81, p < .001; depressive symptoms, ηp 2 = .71, p < .001; and functional impairment, ηp 2 = .42, p = .002. These findings add to a growing body of literature highlighting the preliminary effectiveness of WET across various settings, populations, and delivery formats. Limitations include the small sample size and uncontrolled design.

PMID:38583141 | DOI:10.1002/jts.23042

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Yoga-based lifestyle intervention for healthy ageing in older adults: a two-armed, waitlist randomized controlled trial with multiple primary outcomes

Geroscience. 2024 Apr 7. doi: 10.1007/s11357-024-01149-5. Online ahead of print.

ABSTRACT

Yoga-based clinical research has shown considerable promise in varied ageing-related health outcomes in older adults. However, robust frameworks have yet to be used in intervention research to endorse yoga as a healthy ageing intervention to test the multidimensional construct of healthy ageing. This was an assessor-masked, randomized controlled trial conducted among 258 sedentary, community-dwelling older adults aged 60-80 years, randomly allocated to 26-week yoga-based intervention (YBI) (n = 132) or waitlist control (WLC) (n = 126). The effectiveness of YBI was assessed through two separate global statistical tests, generalized estimating equations and rank sum-based test, against a comprehensive healthy aging panel comprised of ten markers representing the domains of physiological and metabolic, cognitive, physical capability, psychological, and social well-being. The secondary outcomes were individual primary marker scores, Klotho, inflammatory markers, and auxiliary blood markers. We could establish the healthy aging effect of the 26-week YBI over WLC using two models of global statistical test (GEE, β = 0.29; 95% CI = 0.20 to 0.38, p < 0.001), and rank sum-based test (β = 0.28, 95% CI = 0.19 to 0.36, p < 0.001). There were also significant improvements in direction of benefit at individual levels of all the aging markers. Exploratory evaluation with adopted indices from contemporary clinical trials also validated the potential of YBI for healthy aging; HATICE adapted composite score (mean difference = – 0.18; 95% CI = – 0.26 to – 0.09, p < 0.001) and healthy ageing index (mean difference = – 0.33; 95% CI = – 0.63 to – 0.02, p = 0.03). The global effect of YBI across multiple ageing-related outcomes provides a proof of concept for further large-scale validation. The findings hold a great translational value given the accelerated pace of population aging across the globe. Trial registration: CTRI/2021/02/031373.

PMID:38583114 | DOI:10.1007/s11357-024-01149-5

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Value of Information for Clinical Trial Design: The Importance of Considering All Relevant Comparators

Pharmacoeconomics. 2024 Apr 7. doi: 10.1007/s40273-024-01372-0. Online ahead of print.

ABSTRACT

Value of Information (VOI) analyses calculate the economic value that could be generated by obtaining further information to reduce uncertainty in a health economic decision model. VOI has been suggested as a tool for research prioritisation and trial design as it can highlight economically valuable avenues for future research. Recent methodological advances have made it increasingly feasible to use VOI in practice for research; however, there are critical differences between the VOI approach and the standard methods used to design research studies such as clinical trials. We aimed to highlight key differences between the research design approach based on VOI and standard clinical trial design methods, in particular the importance of considering the full decision context. We present two hypothetical examples to demonstrate that VOI methods are only accurate when (1) all feasible comparators are included in the decision model when designing research, and (2) all comparators are retained in the decision model once the data have been collected and a final treatment recommendation is made. Omitting comparators from either the design or analysis phase of research when using VOI methods can lead to incorrect trial designs and/or treatment recommendations. Overall, we conclude that incorrectly specifying the health economic model by ignoring potential comparators can lead to misleading VOI results and potentially waste scarce research resources.

PMID:38583100 | DOI:10.1007/s40273-024-01372-0

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A novel scoring system for early prediction of massive transfusion requirement in trauma patients

Intern Emerg Med. 2024 Apr 7. doi: 10.1007/s11739-024-03541-7. Online ahead of print.

ABSTRACT

Early resuscitation using blood products is critical for patients with severe hemorrhagic shock. We aimed to develop and validate a new scoring system, hemorrhagic shock transfusion prediction (HSTP) score, to predict the need for massive transfusion (MT) in these patients, compared to the widely used Assessment of Blood Consumption (ABC) score. Trauma patients admitted to Emtiaz Hospital in Iran from 2017 to 2021 were retrospectively included. Patients assigned a code 1 or 2 according to the Emergency severity index (ESI) triage system have been divided into MT and non-MT groups. MT was defined as receiving ≥ 10 units of packed cells (PCs) in 24 h. Demographic information, admission vital signs, and lab results available within 15 min were compared between the groups. A new predictive score was developed using logistic regression of statistically significant parameters. Out of 1029 patients, 651 (63.3%) required MT. An arrival, diastolic blood pressure < 79.5 mm Hg, absolute lymphocyte count > 1850/μL, base excess < – 4.25, and blood glucose > 156 mg/dL were independent predictors included in the HSTP score. The sensitivity and specificity were 74.36% and 53.87% for the HSTP score, compared to 31.03% and 76.16% for the ABC score. Moreover, the positive and negative predictive values were 77.88% and 49.03% for the HSTP score, versus 74.15% and 33.66% for ABC. The new scoring system demonstrated higher sensitivity and improved positive and negative predictive values compared to the ABC score. This score can assist physicians in making accurate transfusion decisions quickly, but further prospective studies are warranted to validate its clinical utility.

PMID:38583098 | DOI:10.1007/s11739-024-03541-7

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Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia: The SHASTA-2 Randomized Clinical Trial

JAMA Cardiol. 2024 Apr 7. doi: 10.1001/jamacardio.2024.0959. Online ahead of print.

ABSTRACT

IMPORTANCE: Severe hypertriglyceridemia (sHTG) confers increased risk of atherosclerotic cardiovascular disease (ASCVD), nonalcoholic steatohepatitis, and acute pancreatitis. Despite available treatments, persistent ASCVD and acute pancreatitis-associated morbidity from sHTG remains.

OBJECTIVE: To determine the tolerability, efficacy, and dose of plozasiran, an APOC3-targeted small interfering-RNA (siRNA) drug, for lowering triglyceride and apolipoprotein C3 (APOC3, regulator of triglyceride metabolism) levels and evaluate its effects on other lipid parameters in patients with sHTG.

DESIGN, SETTING, AND PARTICIPANTS: The Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia (SHASTA-2) was a placebo-controlled, double-blind, dose-ranging, phase 2b randomized clinical trial enrolling adults with sHTG at 74 centers across the US, Europe, New Zealand, Australia, and Canada from May 31, 2021, to August 31, 2023. Eligible patients had fasting triglyceride levels in the range of 500 to 4000 mg/dL (to convert to millimoles per liter, multiply by 0.0113) while receiving stable lipid-lowering treatment.

INTERVENTIONS: Participants received 2 subcutaneous doses of plozasiran (10, 25, or 50 mg) or matched placebo on day 1 and at week 12 and were followed up through week 48.

MAIN OUTCOMES AND MEASURES: The primary end point evaluated the placebo-subtracted difference in means of percentage triglyceride change at week 24. Mixed-model repeated measures were used for statistical modeling.

RESULTS: Of 229 patients, 226 (mean [SD] age, 55 [11] years; 176 male [78%]) were included in the primary analysis. Baseline mean (SD) triglyceride level was 897 (625) mg/dL and plasma APOC3 level was 32 (16) mg/dL. Plozasiran induced significant dose-dependent placebo-adjusted least squares (LS)-mean reductions in triglyceride levels (primary end point) of -57% (95% CI, -71.9% to -42.1%; P < .001), driven by placebo-adjusted reductions in APOC3 of -77% (95% CI, -89.1% to -65.8%; P < .001) at week 24 with the highest dose. Among plozasiran-treated patients, 144 of 159 (90.6%) achieved a triglyceride level of less than 500 mg/dL. Plozasiran was associated with dose-dependent increases in low-density lipoprotein cholesterol (LDL-C) level, which was significant in patients receiving the highest dose (placebo-adjusted LS-mean increase 60% (95% CI, 31%-89%; P < .001). However, apolipoprotein B (ApoB) levels did not increase, and non-high-density lipoprotein cholesterol (HDL-C) levels decreased significantly at all doses, with a placebo-adjusted change of -20% at the highest dose. There were also significant durable reductions in remnant cholesterol and ApoB48 as well as increases in HDL-C level through week 48. Adverse event rates were similar in plozasiran-treated patients vs placebo. Serious adverse events were mild to moderate, not considered treatment related, and none led to discontinuation or death.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of patients with sHTG, plozasiran decreased triglyceride levels, which fell below the 500 mg/dL threshold of acute pancreatitis risk in most participants. Other triglyceride-related lipoprotein parameters improved. An increase in LDL-C level was observed but with no change in ApoB level and a decrease in non-HDL-C level. The safety profile was generally favorable at all doses. Additional studies will be required to determine whether plozasiran favorably modulates the risk of sHTG-associated complications.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04720534.

PMID:38583092 | DOI:10.1001/jamacardio.2024.0959

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The impact of augmented reality glasses on human visual efficiency and digital eye fatigue

Zhonghua Yan Ke Za Zhi. 2024 Apr 11;60(4):352-358. doi: 10.3760/cma.j.cn112142-20231122-000246.

ABSTRACT

Objective: To investigate the differences in reading efficiency and visual fatigue between the use of augmented reality (AR) glasses and laptops. Methods: A prospective self-controlled study was conducted. Healthy students from Capital Medical University who frequently engaged in long-term near work and used laptops and other digital display devices were recruited as subjects at Beijing Tongren Hospital, Capital Medical University between November 1 and November 15, 2023. LogMAR visual acuity, visual functions (accommodation, convergence, and fusion), and visual fatigue scores (Likert visual fatigue scale) of the participants were assessed. The order of using the laptop and AR glasses for each participant was determined by a coin toss. Reading efficiency (reading speed and error rate multiplied by the detection rate of incorrect numbers) with different devices for 10 minutes at the same time on different dates and visual fatigue scores after watching a 20-minute video were measured. Statistical analyses were performed using paired t-tests and Wilcoxon signed-rank tests. Results: A total of 20 eligible subjects were included, comprising 7 males and 13 females, with a mean age of (25.45±2.27) years. There was no significant change in binocular visual acuity before and after using AR glasses and laptops (both P>0.05). The reading speed and reading efficiency of using AR glasses [(34.03±9.25) and (29.19±7.62) digits/min, respectively] were significantly lower than those of using laptops [(39.43±10.36) and (35.67±9.87) digits/min, respectively] (t=4.36, P<0.001), while the difference in error detection rate was not statistically significant (t=1.29, P=0.213). There was no statistically significant difference in visual fatigue scores before watching videos with the two devices (Z=-0.71, P=0.480). However, the visual fatigue score after watching videos with AR glasses [(20.55±5.04) points] was significantly higher than that with laptops [16.50 (13.00, 19.75) points] (Z=-2.85, P=0.004). The visual fatigue scores after watching videos with both devices were significantly higher than before (P<0.05), with a more significant increase observed with AR glasses [(6.05±3.50) points] (Z=-3.41, P<0.001). Conclusion: Compared with using laptops, the reading speed and efficiency were lower, and the visual fatigue was more pronounced with the use of AR glasses at the current technical level. Further optimization and improvement of AR glasses are warranted.

PMID:38583059 | DOI:10.3760/cma.j.cn112142-20231122-000246