Early Administration Research Articles

Stepping Back: How Should Pass/Fail Scoring Influence Step 1 Timing?

Although most students complete Step 1 before clerkships, some institutions delay the exam until after clerkships. The change to pass/fail grading adds additional complexity that should be considered when deciding about exam timing. Both early and late administration may affect learning outcomes, learner behavior, student well-being, and residency match success. Step 1 completion before clerkships promotes learning outcomes (e.g., integration and mastery of foundational material), may encourage students to focus on the curriculum, and may better prepare students for clinical science exams (CSEs). However, delaying the exam ensures that students maintain foundational knowledge and may encourage clinical educators to demonstrate basic science illustrations. An early Step 1 may affect learner behavior by allowing clerkship students to focus on clinical learning. The associated National Board of Medical Examiners performance report may also be used for Step 2 and CSE preparation. However, delaying Step 1 allows greater scheduling flexibility based on developmental milestones. Administration of Step 1 before clerkships removes a significant stressor from the clinical year and decompresses the residency application period. However, a delayed Step 1 reduces the pressure on students to engage in numerous extracurricular and research activities to distinguish themselves due to the pass/fail change. An early Step 1 exam may also lead to improved CSE performance, which is often linked to clerkship honors criteria, an increasingly valuable distinction for residency match success after the change to pass/fail. In contrast, delaying Step 1 is associated with higher first-time pass rates, which may be especially important for students at risk for failure. Medical educators and students should collaboratively approach the question of Step 1 timing, considering these factors within the context of the medical school program, curricular constraints and priorities, and students' individual needs and goals.

POSITIVE IMPACT OF TRANEXAMIC ACID IN VARIOUS MEDICAL SETTINGS

The role of successful hemostasis cannot be overemphasized. Bleeding can occur due to various reasons and its cause is not always evident. Any delay in restoring the proper hemostasis is associated with increased risk of complications and therefore results in increased mortality. Discovered in 1962 by Japanese researchers Shosuke and Utako Okamoto, tranexamic acid (TXA) is an anti-fibrinolytic agent that inhibits plasminogen activation by blocking the lysine binding sites on plasminogen. Thanks to its ability to inhibit fibrinolysis it stabilizes the preformed fibrin mesh-work and has a beneficial effect in reducing blood loss in wide range of clinical settings. TXA has been shown to reduce the risk of perioperative bleeding in patients undergoing noncardiac surgeries. CRASH trials provided the largest body of evidence confirming effectiveness of early administration of TXA, defined as administration within 3 hours after trauma, in reducing mortality in patients with severe injuries and traumatic brain injury. Recent evidence indicates that TXA administration in treatment of postpartum hemorrhage results in notable mortality reduction. Topical or locally injected tranexamic acid may reduce blood loss and improve visibility of the surgical field. More high-quality studies are needed to determine safety, efficacy and dosage. The risk of serious adverse events, especially vascular occlusive events, in patients receiving TXA compared to placebo group did not differ significantly.

Strategies for early adrenaline administration using a kitchen timer for time management

Strategies for early adrenaline administration using a kitchen timer for time management

Effectiveness of combination therapy with intrathecal or intraventricular administration of polymyxin B for hospital-acquired central nervous system infections caused by carbapenem-resistant Acinetobacter baumannii: A retrospective study

To evaluate the therapeutic regimen, efficacy and safety of intrathecal or intraventricular (ITH/IVT) administration of polymyxin B for hospital-acquired central nervous system (CNS) infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). A retrospective study was undertaken of patients with CNS infections caused by CRAB treated with ITH/IVT combination therapy. The primary outcome was the clinical efficacy of treatment. The secondary outcomes were the bacterial clearance rate and the safety of therapy. In total, 35 patients who received ITH [n=13 (37.1%)] or IVT [n=22 (62.9%)] polymyxin B as combination therapy were included in this study. The median duration of ITH/IVT polymyxin B therapy was 9 (interquartile range 7-11) days. The overall clinical cure rate and bacterial clearance rate were 77.1% and 85.7%, respectively. No adverse effects considered to be related to ITH/IVT polymyxin B were recorded. Clinical failure was independently associated with an Acute Physiology and Chronic Health Evaluation II score ≥15 [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.05-1.42; P=0.038] and a Glasgow Coma Scale score ≤8 (OR 0.69, 95% CI 0.49-0.88; P=0.029). Early administration (≤4 days of infection onset) of ITH/IVT polymyxin B therapy resulted in a significantly higher clinical cure rate (OR 0.65, 95% CI 0.49-1.12; P<0.001), and may reduce the length of treatment and adverse effects. ITH/IVT administration of polymyxin B is a valid alternative for the treatment of CNS infections caused by CRAB. Early use of ITH/IVT polymyxin B can result in greater clinical success.

Botulinum toxin-A in acute acquired comitant esotropia during COVID pandemic in children and young adolescents

Abstract Purpose: To study the effectiveness of botulinum toxin A (BTX-A) in the treatment of patients with acute acquired comitant esotropia (AACE) due to excessive use of mobile and laptops in the COVID era in the pediatric population and adolescents. Methods: This was a retrospective, interventional study of pediatric patients and young adults who presented with AACE and received unilateral or bilateral BTX-A. All the patients complained of binocular diplopia and sudden onset of esotropia with a history of mobile or laptop usage during the COVID era (2020–2023). Twenty-seven patients with acute-onset esotropia in 3 years (2020–2023) were included. All patients were administered 2.5–7.5 units of BTX-A (Botox, Allergan, India) into the unilateral or bilateral medial rectus muscle of the deviating eye under short general anesthesia or local anesthesia. The main outcome measures were pre- and post-injection angle of deviation, pre- and post-injection stereopsis, final level of stereopsis achieved, recurrence, and whether strabismus surgery was later required. Results: The mean age of patients was 12.85 ± 7.15 years (range: 4–25 years). The mean dosage of Botox was 6 U (2.5–7.5 U). The mean follow-up was 6 months (6 months–2 years). The mean preoperative angle of deviation (AOD) was 41.11 ± 10.9 prism diopters (PD) for distance and 41.67 ± 10.9 PD for near. The maximum effect of BTX-A was seen at 1 month; post-injection AOD was 13.65 ± 14.7 PD for distance and 14.87 ± 15.8 PD for near (P &lt; 0.001). Over half of the patients achieved optimal outcomes, with improvements in stereopsis and sensory fusion. Early intervention (within 3 months of symptom onset) significantly correlated with treatment success. Conclusion: While BTX-A therapy for acute-onset esotropia demonstrates efficacy, patient-specific considerations are essential. This study highlights the evolving nature in the digital age and early administration of BTX-A along with close follow-up to monitor residual and recurrence of esotropia. The surgical intervention can increase the final success rate.

Efficacy of a mitochondrial drug cocktail in preventing acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is difficult to differentiate from prolonged febrile seizures during the acute phase. Mitochondrial dysfunction-induced energy depletion is among the key mechanisms underlying acute encephalopathy. Therefore, this study aimed to examine the efficacy of a “mitochondrial cocktail” in preventing AESD. We retrospectively studied children experiencing status epilepticus associated with fever lasting more than 30 min, focusing on those who received the mitochondrial cocktail between February 2016 and December 2020, and those who did not receive it within 24 h between February 2012 and January 2014. The mitochondrial cocktail contained vitamins B1, C, and E; biotin; coenzyme Q10; and l-carnitine. AESD occurred in 1 of 41 (2.4 %) patients in the administration group and 7 of 39 (17.9 %) patients in the non-administration group. The incidence of AESD was lower in the administration group than in the non-administration group, with a significant difference (p = 0.027). The incidence of encephalopathy, including cases classified as AESD and unclassified, was 7/41 (17.1 %) and 7/39 (17.9 %) in the administration and non-administration groups, respectively, with no significant difference. However, the number of cases with worsening pediatric cerebral performance category scores was significantly lower in the administration group compared to the non-administration group (p = 0.015). In conclusion, early administration of the mitochondrial cocktail may help prevent AESD. Some encephalopathy cases do not progress to a biphasic state or develop AESD. Thus, the mitochondrial cocktail should be administered as early as possible to prevent AESD.

Gas6/Axl signaling promotes hematoma resolution and motivates protective microglial responses after intracerebral hemorrhage in mice

BackgroundIntracerebral hemorrhage (ICH) stands out as the most fatal subtype of stroke, currently devoid of effective therapy. Recent research underscores the significance of Axl and its ligand growth arrest-specific 6 (Gas6) in normal brain function and a spectrum of neurological disorders, including ICH. This study is designed to delve into the role of Gas6/Axl signaling in facilitating hematoma clearance and neuroinflammation resolution following ICH. MethodsAdult male C57BL/6 mice were randomly assigned to sham and ICH groups. ICH was induced by intrastriatal injection of autologous arterial blood. Recombinant mouse Gas6 (rmGas6) was administered intracerebroventricularly 30 min after ICH. Virus-induced knockdown of Axl or R428 (a selective inhibitor of Axl) treatment was administrated before ICH induction to investigate the protective mechanisms. Molecular changes were assessed using western blot, enzyme-linked immunosorbent assay and immunohistochemistry. Coronal brain slices, brain water content and neurobehavioral tests were employed to evaluate histological and neurofunctional outcomes, respectively. Primary glia cultures and erythrophagocytosis assays were applied for mechanistic studies. ResultsThe expression of Axl increased at 12 h after ICH, peaking on day 3. Gas6 expression did not remarkably changed until day 3 post-ICH. Early administration of rmGas6 following ICH significantly reduced hematoma volume, mitigated brain edema, and restored neurological function. Both Axl-knockdown and Axl inhibitor treatment abolished the neuroprotection of exogenous Gas6 in ICH. In vitro studies demonstrated that microglia exhibited higher capacity for phagocytosing eryptotic erythrocytes compared to normal erythrocytes, a process reversed by blocking the externalized phosphatidylserine on eryptotic erythrocytes. The erythrophagocytosis by microglia was Axl-mediated and Gas6-dependent. Augmentation of Gas6/Axl signaling attenuated neuroinflammation and drove microglia towards pro-resolving phenotype. ConclusionsThis study demonstrated the beneficial effects of recombinant Gas6 on hematoma resolution, alleviation of neuroinflammation, and neurofunctional recovery in an animal model of ICH. These effects were primarily mediated by the phagocytotic role of Axl expressed on microglia.

Safety and efficacy of early beta-blocker initiation in acute heart failure and cardiogenic shock: systematic review and meta-analysis

BackgroundThe beta-blocker (BB) initiation in acute heart failure (AHF) patients is still controversial. Some show the benefit of BB employment in decreasing the mortality outcome. This study aims to assess the safety and efficacy of in-hospital and long-term outcomes of BB initiation in AHF hospitalized patients. We searched multiple databases examining the outcome of AHF patients who had administered BB as the therapy initiation. Primary outcomes were all-cause mortality, composite endpoint after BB initiation when hospitalized, and post-discharge all-cause mortality. The secondary outcomes were adverse events after in-hospital BB initiation, including hypotension and symptomatic bradycardia after BB initiation when hospitalization and rehospitalization.ResultsEight cohort studies with 16,639 patients suffering from AHF and cardiogenic shock, with 9923 participants allocated to the early BB group and 6,713 patients in the control group. The follow-up durations ranged from 2 to 24 months. Early BB administration significantly reduced in-hospital composite endpoints (RR: 0.42; 95% CI (0.30–0.58); p < 0.001), in-hospital all-cause mortality (RR: 0.43; 95% CI (0.31–0.61); p < 0.001), discharge mortality (RR: 0.51; 95% CI (0.41–0.63); p < 0.001), and rehospitalization (RR: 0.57; 95% CI (0.44–0.74); p < 0.001). There were no discernible differences in in-hospital BB-related adverse events between the two groups (p = 0.13). Subgroup analyses conducted on AHF patients presenting with cardiogenic shock revealed no significant differences in in-hospital composite endpoint and in-hospital mortality, and similar results were shown in the naive BB population.ConclusionsThe BB initiation in AHF patients shows advantages in efficacy and safety outcome.

Early High-Dose Erythropoietin and Cognitive Functions of School-Aged Children Born Very Preterm

Children born very preterm are at risk for long-term neurodevelopmental sequelae. Prophylactic high-dose recombinant human erythropoietin (rhEpo) shortly after birth has not been shown to improve cognitive, motor, and behavioral development at 2 and 5 years. To investigate whether early high-dose rhEpo is associated with better executive functions and processing speed-late-maturing cognitive functions-in school-aged children born very preterm. This single-center cohort study was a prospective, observational follow-up study of a multicenter neonatal clinical trial; 365 children born very preterm (mean gestational age, 29.3 weeks [range, 26.0-31.9 weeks]) who had been enrolled in the Swiss EPO Neuroprotection Trial at birth between 2005 and 2012, and who were included in the primary outcome analyses at 2 years, were eligible to be recruited for the EpoKids study between 2017 and 2021 when they were at school age. Term-born children were additionally recruited and included in a control group. Data were analyzed between May and September 2022. Administration of rhEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 2 days of life as part of the Swiss EPO Neuroprotection Trial. A comprehensive neuropsychological test battery assessed executive functions and processing speed, and parents reported on their child's executive functions in everyday life to test the hypothesis that early high-dose rhEpo administration is associated with better cognitive outcomes at school age. In the EpoKids study, 214 children born very preterm (58.6% of 365 children in eligible cohort) were assessed at a mean age of 10.4 years (range, 6.9-13.4 years); 117 (54.7%) were boys. There was no evidence that the 117 children who had received rhEpo differed from the 97 children who had received placebo in any of the 15 executive function and processing speed tests, nor in parent-rated executive functions (estimates ranged from -0.138 to 0.084, all 95% CIs included 0). Irrespective of rhEpo or placebo allocation, children born very preterm scored lower on 11 of 15 executive function and processing speed tests than term-born peers (estimates ranged from 0.112 to 0.255, 95% CIs did not include 0). This study found no evidence for a positive association between prophylactic early high-dose rhEpo administration and long-term neurodevelopmental outcomes after very preterm birth. These results suggest that a comprehensive approach, including pharmacological and nonpharmacological prevention and intervention strategies, is needed to support these children's neurodevelopmental outcome.

РАННИЕ РЕЗУЛЬТАТЫ ТЕРАПИИ ИНГИБИТОРОМ НГЛТ-2 ДАПАГЛИФЛОЗИНОМ БОЛЬНЫХ С ОСТРОЙ ДЕКОМПЕНСАЦИЕЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Acute decompensation of heart failure is one of the main causes of repeated hospitalizations and worse survival rate. Studies aimed at exploring new opportunities to improve clinical status and prognosis remain highly relevant. Early administration of the type 2 sodium-glucose cotransporter inhibitors (iNGLT-2), in particular dapagliflozin, looks promising.

Early Versus Late Administration of Long-Acting Insulin in Adult Diabetic Ketoacidosis.

Evidence is inconclusive if early administration of subcutaneous (SQ) long-acting insulin (LAI) in management of diabetic ketoacidosis (DKA) improves outcomes. This study compares early versus late administration of SQ LAI in time to DKA resolution. This single-center, retrospective study included patients with DKA who received ≥12 hours of continuous intravenous insulin (CIVI) with LAI overlap. Patients were compared based on LAI administration time to CIVI initiation: Early (<12 hours) versus Late (≥12 hours). The DKA resolution is defined as blood glucose < 200 mg/dL and 2 of the following: anion gap < 12 mEq/L, pH > 7.35, or serum carbon dioxide >15 mEq/L. Outcomes included time to DKA resolution, length of stay (LOS), CIVI duration, and adverse events. A total of 27 patients were included in each group. Baseline characteristics were similar between both groups. There was no difference in time to DKA resolution, Early = 17.6 (13.9-26.8) hours versus Late = 19.2 (17.1-32.1) hours, P = 0.16. The Early group had shorter CIVI duration (Early = 19.5 ± 10.3 hours vs Late = 25.6 ± 8.4 hours, P = 0.02) and received less intravenous (IV) fluids in the first 36 hours (Early = 4.04 ± 2.12 L vs Late = 5.85 ± 2.24 L, P = 0.004). No differences were identified with adverse events, including hypoglycemia, or LOS. Administration of SQ LAI < 12 hours did not decrease time to DKA resolution or LOS. Patients in the Early group had received a lower dose of LAI, shorter duration of CIVI infusion, and required less IV fluids within 36 hours of admission. This study supports the need for further research to determine the potential benefits of administering SQ insulin early in managing DKA.

Real-world analysis on the use of gamma-hydroxybutyric acid for alcohol withdrawal syndrome in hospitalized patients with diagnosis of cirrhosis.

The present real-world analysis aimed to evaluate and describe the use of gamma-hydroxybutyric acid (GHB) for alcohol withdrawal syndrome (AWS) in hospitalized patients with diagnosis of liver cirrhosis. An 11-year observational retrospective study on patients affected by liver cirrhosis and alcohol use disorder (AUD) was performed using data from the Medical Toxicology Unit of Careggi University Hospital in Florence (Italy). A multivariate logistic regression was performed to estimate the probability of having a CIWA-Ar Max 3-4 during hospitalization, an AWS length > 36h, a hospitalization > 9days, and the probability of developing drowsiness. A total of 166 AUD patients were included, of these 77 received GHB (70.13% within the first day of hospitalization) and 89 were treated without GHB. The majority were ≥ 40years of age (87.35%) and males (80.12%). GHB patients were more likely to have a CIWA-Ar Max 3-4 during hospitalization (OR 3.76 [CI 95% 1.02-13.85]), and a longer hospitalization (OR 3.08 [95% CI 1.23-7.71]). Early GHB administration decreased the probability of CIWA-Ar Max worsening (OR 0.06 [95% CI 0.01-0.49]). GHB dose ≥ 100mg/kg was not associated with the occurrence of drowsiness. Patients exposed to other sedative agents were more likely to experience drowsiness (OR 7.22 [95% CI 1.46-35.61]). The present real-world analysis underlines that GHB could be a valuable and safe option for the management of AWS in AUD patients affected by liver cirrhosis, also when administered early and even at higher than recommended dosages.

Clinical and laboratory features of juvenile idiopathic arthritis with wrist involvement: Results of a retrospective cohort study.

Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis (JIA) with progressive disease course, polyarticular involvement and failure of methotrexate treatment. To describe features of JIA, associated with wrist arthritis. Data from about 753 JIA patients were included in this retrospective cohort study. The clinical and laboratory features of patients with and without wrist involvement were analyzed. Wrist involvement was found in oligoarthritis (5.8%), RF(-)/RF(+) polyarthritis (44.9%/15.0%), enthesitis-related arthritis (17.7%), and systemic (58.6%) JIA categories. Unilateral wrist involvement was typical for oligoarthritis patients, bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories. Wrist arthritis was found to be associated with female sex, a low incidence of uveitis, and more indications of systemic inflammation, including elevated levels of C-reactive protein, erythrocyte sedimentation rate, and platelets, as well as involvement of the cervical spine, temporomandibular, shoulder, elbow, metacarpophalangeal, proximal interphalangeal, distal interphalangeal, hip, ankle, and tarsus arthritis. The number of patients with hip osteoarthritis and hip replacement was also higher. Wrist arthritis was associated with a lower probability of achieving remission [hazard ratio (HR) = 1.3 (95%CI: 1.0-1.7), P = 0.055], and a higher probability of being treated with biologics [HR = 1.7 (95%CI: 1.3-2.10, P = 0.00009)]. Wrist arthritis in JIA patients is a marker of a severe disease course, characterized by more intensive inflammation, unfavorable outcomes, and. requiring more intensive treatment with early administration of biologics. Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.

Examination of the Suitability of Vericiguat in Non-Heart Failure with Preserved Ejection Fraction Patients with Improved Ejection Fraction.

Background/Objectives: Vericiguat has been shown to reduce cardiovascular mortality and hospitalisation for heart failure in patients with reduced ejection fraction. While Vericiguat is considered one of the standard treatments for heart failure, it is unclear under which conditions Vericiguat would be most effective. With a focus on the prognosis and improved EF of heart failure, we aimed to investigate in which cases Vericiguat is suitable for use in addition to standard cardioprotective drugs. Methods: We prospectively compared echocardiograms taken before and after the administration of Vericiguat in 46 patients with non-dialysis and without heart failure with preserved ejection fraction (non-HFpEF) (left ventricle ejection fraction [LVEF] < 50%) who were able to continue Vericiguat in addition to other standard heart failure drugs (the "Fantastic Four") for more than 6 months at our hospital. Patients who showed an improvement of 10 points or more in LVEF were defined as improved EF+. Results: LVEF improved significantly from 38 [33-45]% at the time of administration to 46 [35-54.5]% at 6 months (p < 0.001). When comparing patients with and without improved EF, a significant difference was observed in the Hb (OR = 1.66, 95%CI = 1.12-2.83, p = 0.028), early introduction (OR = 12.5, 95%CI = 1.58-149, p = 0.025), and initiation of Vericiguat after the administration of the Fantastic Four (OR = 9.79, 95%CI = 1.71-100.2, p = 0.022). Conclusions: In this study, the early administration of Vericiguat, haemoglobin value, and initiation of Vericiguat after the introduction of the Fantastic Four were identified as independent factors for eligibility in non-dialysis, non-HFpEF patients who were able to continue GDMT treatment for more than 6 months after adding Vericiguat.

Early Prediction and Streamline of Nucleophosmin Mutation Status in Acute Myeloid Leukemia Using Cup-Like Nuclear Morphology.

Background and Objectives: With the advent of novel therapies for nucleophosmin gene (NPM1)-mutated acute myeloid leukemia (AML), there is a growing need for the reliable prediction of NPM1 mutations. This study explored the role of cytomorphological features in the early prediction of NPM1-mutated AML. Materials and Methods: Altogether, 212 de novo AML cases with normal karyotypes, diagnosed and treated at a single institution within 5 years (2018-2023), were retrospectively evaluated. A final diagnosis of NPM1-mutated AML, based on the World Health Organization (WHO) integrated criteria, including real-time based identification of NPM1 mutation and normal karyotype, was established in 83/212 (39.15%) cases. Results: Cup-like blasts (CLBs), a cytomorphological feature suggestive of NPM1-mutated AML, were detected in 56/83 (67%) patients. Most cases (44/56, 78.6%) had CLB ≥ 10%. In total, 27 of 83 AML NPM1-mutated patients had no CLB morphology (missed call). Additionally, two of 212 had CLB morphology without confirmed NPM1 mutation (wrong call). The positive/negative predictive values of cytomorphological evaluation for CLB ≥ 10% were 95.7%/75.6%, with sensitivity/specificity of 53%/98.5%, while the accuracy was 80.7%. We noted an increased percentage of CLBs (≥15%) in 77.8% and 50% of patients with AML without and with granulocytic maturation, respectively (the specificity for NPM1 mutation prediction was 100%). CLB was associated with fms-like tyrosine kinase 3 (FLT3) mutation (p = 0.03), but, without statistical significance for CLB ≥ 10% and CLB ≥ 15%. Conclusions: Our investigation confirmed that the morphological identification of CLB at diagnosis represents a reliable and easily reproducible tool for the early prediction of NPM1 mutations, enabling a streamlined genetic work-up for its confirmation. This may facilitate considering the early administration of individualized therapies by clinicians for specific patients.

Utilizing deep learning models in an intelligent spiral drawing classification system for Parkinson's disease classification.

Parkinson's disease (PD) is a neurodegenerative illness that impairs normal human movement. The primary cause of PD is the deficiency of dopamine in the human brain. PD also leads to several other challenges, including insomnia, eating disturbances, excessive sleepiness, fluctuations in blood pressure, sexual dysfunction, and other issues. The suggested system is an extremely promising technological strategy that may help medical professionals provide accurate and unbiased disease diagnoses. This is accomplished by utilizing significant and unique traits taken from spiral drawings connected to Parkinson's disease. While PD cannot be cured, early administration of drugs may significantly improve the condition of a patient with PD. An expeditious and accurate clinical classification of PD ensures that efficacious therapeutic interventions can commence promptly, potentially impeding the advancement of the disease and enhancing the quality of life for both patients and their caregivers. Transfer learning models have been applied to diagnose PD by analyzing important and distinctive characteristics extracted from hand-drawn spirals. The studies were carried out in conjunction with a comparison analysis employing 102 spiral drawings. This work enhances current research by analyzing the effectiveness of transfer learning models, including VGG19, InceptionV3, ResNet50v2, and DenseNet169, for identifying PD using hand-drawn spirals. Transfer machine learning models demonstrate highly encouraging outcomes in providing a precise and reliable classification of PD. Actual results demonstrate that the InceptionV3 model achieved a high accuracy of 89% when learning from spiral drawing images and had a superior receiver operating characteristic (ROC) curve value of 95%. The comparison results suggest that PD identification using these models is currently at the forefront of PD research. The dataset will be enlarged, transfer learning strategies will be investigated, and the system's integration into a comprehensive Parkinson's monitoring and evaluation platform will be looked into as future research areas. The results of this study could lead to a better quality of life for Parkinson's sufferers, individualized treatment, and an early classification.

The effect of early administration of antibiotics or feeding a diet containing coccidiostats on the level of their accumulation in liver and the redox status of turkeys

Early administration of antibiotics may worsen the functioning of the turkeys’ antioxidant system. It was also assumed that the longer the time of administration of an antibiotic, e.g. a coccidiostat, the greater the risk of its accumulation in the liver. The study aimed to determine whether early administration of antibiotics or feeding a diet containing coccidiostats causes accumulation in the liver and whether it affects the deterioration of the antioxidant system, and whether preventive vaccinations can intensify it. A total of 3 080 female turkeys were randomly allocated to eight groups. The experiment had a two-factorial design, with four treatments (C, M, E, D) and two groups of birds (vaccinated +, unvaccinated −). The C group did not receive the coccidiostat or antibiotics. Group M was administered monensin at 90 mg/kg feed for 56 days of life. Group E received enrofloxacin at 10 mg/kg BW, and group D received doxycycline at 50 mg/kg BW, added to drinking water, for the first 5 days of life. One-day-old turkeys from groups C+, M+, E+, and D+ were administered live-attenuated vaccines against turkey rhinotracheitis and Newcastle disease by coarse spray; 28-day-old birds were administered a subcutaneously injected inactivated vaccine against Ornithobacterium rhinotracheale. Turkeys from groups C-, M-, E-, and D- were not vaccinated. It was determined that as a result of administration of enrofloxacin or doxycycline until the 5th day of life, biotransformation of these antibiotics occurred in the liver until the 56th day of life of the turkeys, which was confirmed by their lower level than the Maximum Residue Level. Because the concentration of monensin in the liver of turkeys gradually increased with the extension of the time of its administration in the diet, it is probable that discontinuing its addition a day before the slaughter of birds will result in the presence of this coccidiostat in the liver of turkeys. Despite the accumulation of monensin in the liver of turkeys, this coccidiostat did not increase oxidative reactions in the organism of turkeys. Vaccination of turkeys can reduce oxidative reactions and apoptosis in the body. However, the effect of the redox system reaction is different immediately after vaccination, which is due to the mechanism of action of the immune system. If it is necessary to administer an antibiotic in the early rearing period, the effects of doxycycline on the organism’s immunity including antioxidant defence will be less severe than those of enrofloxacin.

The Efficacy and Safety of Inclisiran for Low-Density Lipoprotein (LDL) in Patients With Atherosclerotic Cardiovascular Disease (ASCVD): A Systematic Review of Randomized Controlled Trials.

This systematic review synthesizes current evidence to evaluate the safety and efficacy of inclisiran for lowering low-density lipoproteincholesterol (LDL-C). A thorough search was conducted across four main databases -PubMed, Web of Science, SCOPUS, and Science Direct - for relevant studies published in the literature within the last five years (2020-2024).We included seven studies with a total of 6831 participants, of which 4661 (68.2%) were males. The follow-up duration ranged from 60to 1350 days. The intervention we focused on was a subcutaneous injection of inclisiran (284 mg) in the seven trials. Of the total population, 2411 (35%) had diabetes mellitus (DM) and 5335 (78.1%) had hypertension (HTN). The seven trials documented a significant reduction in the mean LDL-C level following the inclisiran application. Early inclisiran administration recorded better results. Inclisiran was found to be efficient, safe, and tolerable among atherosclerotic cardiovascular disease (ASCVD) patients.An inclisiran regimen of 284 mg proved to be efficacious and safe for reducing ASCVD. Most of the affected participants were males and hypertensive. Our findings highlight the need for additional clinical trials to examine inclisiran's safety and effectiveness with regard to cardiovascular outcomes. Extended surveillance studies may yield deeper insights into the efficacy, durability, and tolerability of inclisiran.

Poppy intoxication in children: The interest of early administration of naloxone

In Morocco, medicinal plants are widely used because of their availability, accessibility, and the general public's impression that these remedies are harmless. However, the indiscriminate use of plant agents can lead to serious side effects and even death. Papaver somniferum (opium poppy) is commonly used for its therapeutic properties, as well as for its sedative effects. We report the case of a two-month-old infant who developed respiratory distress and hypotonia after his mother administered an oral preparation of opium poppy to calm him and help him sleep at a family party. The infant recovered well with early supportive and antidotal treatment. This case is reported for three reasons:To draw attention to these widespread dangerous practices among parents in order to make them aware of the risks that may endanger the lives of their children.To alert healthcare professionals to the potential exposure to such substances, which should be considered in cases of unexplained distress in newborns or infants.To highlight the importance of the availability and rapid administration of antidotal treatment.

Efficacy and safety of a step-down regimen of low dosage of glucocorticoids combined with early administration of synthetic or biologic immunosuppressants in anti-synthetase syndrome: A pilot study

IntroductionAnti-synthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of anti-aminoacyl-transfer-RNA synthetase antibodies (ARS) and the involvement of muscles, skin, joints, and lungs. Despite increasing interest and evidence, optimal clinical management remains unclear due to a lack of randomized control trials. This study aims to evaluate the efficacy and safety of a treatment regimen involving early co-administration of glucocorticoids and immunosuppressants, with rapid prednisone tapering. Materials and methodsWe prospectively enrolled patients referred to our multidisciplinary “Myositis Clinic” with a diagnosis of ASS. Clinical, serological, instrumental and medications data were collected at baseline and at 6 and 12 months follow-up. According to treatment protocol, patients were treated with traditional synthetic immunosuppressants or rituximab (RTX) depending on clinical manifestations. Prednisone (PDN) was gradually tapered and eventually discontinued within 6 or 12 months. ResultsA total of twenty-seven subjects were enrolled: arthritis, myositis and ILD were assessed in 9, 16 and 18 patients, respectively, and all of them had an active disease. RTX was administered after methotrexate (MTX) in 4 cases of refractory joint involvement and co-administration of a second immunosuppressant was necessary in 2 patients. When muscle involvement was present, first-line therapy was MTX, followed by mycophenolate mofetil (MMF) or RTX, which allowed to achieve low disease activity or remission, respectively. Eight ILD-patients were treated with MMF and switched to RTX in 5 cases of inefficacy, but all patients were in clinical remission at the end of follow-up. At 12 months, 12 patients discontinued PDN. ConclusionsThis study is the first to prospectively report on the efficacy and safety of a stepwise, steroid-sparing treatment ASS encompassing various domains. MTX, as well as other synthetic immunosuppressants, showed limited efficacy in ASS-related arthritis, while RTX emerged as a promising option. This study recommends early RTX use in case of arthritis, suggesting it as a pivotal treatment for ILD too, and raises questions regarding maintenance therapy and treatment-free remission.