Clinical Trial Study Research Articles

Scalp Nerve Block for Enhanced Pain Control and Analgesic Optimization in Elective Craniotomy: A Randomized Controlled Trial with Analgesia Nociception Index Monitoring

In patients who are candidates for craniotomy, scalp nerve blocks have been shown to be effective in relieving pain intensity as well as postoperative hemodynamic stability after surgery, but the results have been inconsistent. We aimed to assess the effect of scalp block on pain control, intraoperative drug use under Analgesia Nociception Index (ANI) monitoring, and postoperative pain in patients who were candidates for elective craniotomy. In this randomized, single-blinded clinical trial study, candidates for craniotomy were randomly (using the block randomization method) divided into 2 groups before entering the operating room. The first group received a scalp block with bupivacaine (intervention), and the second group did not receive a scalp block (control) besides the routine anesthetic procedure in these patients. ANI, hemodynamic parameters, and the amounts of received remifentanil were conducted and compared. Patients under scalp block received less dosage of fentanyl than the nonscalp block group (mean=57.14±15.59 mcg vs. 250.00±65.04 mcg, respectively). Similarly, the dose of remifentanil required in the scalp block group was less (mean=3.04±1.95mg and 5.54±2.57mg, respectively). No difference was observed in hemodynamic parameters such as blood pressure and heart rate (before, during, and after surgery). However, the group receiving scalp block had higher ANI means than the control group. Scalp nerve block has an effective role in pain control (increasing ANI), consequently reducing the need for analgesic drugs such as fentanyl and remifentanil following craniotomy without changing the hemodynamic condition.

Beyond Immune Checkpoint Inhibitors: Emerging Targets in Melanoma Therapy.

This review provides a comprehensive update on recent advancements in melanoma treatment by highlighting promising therapeutics with an aim to increase awareness of novel interventions currently in development. Over the last decade there has been considerable expansion of the previously available treatment options for patients with melanoma. In particular, novel immunotherapeutics have been developed to expand on the clinical advancements brought by BRAF targeting and immune checkpoint inhibitors. Despite the success of checkpoint inhibitors there remains an unmet need for patients that do not respond to treatment. This review delves into the latest advancements in novel checkpoint inhibitors, cytokines, oncolytic viruses, vaccines, bispecific antibodies, and adoptive cell therapy. Preclinical experiments and early-stage clinical trials studies have demonstrated promising results for these therapies, many of which have moved into pivotal, phase 3 studies.

High potency of linalool-zinc oxide nanocomposite as a new agent for cystic echinococcosis treatment.

This current in vitro, ex vivo, and in vivo research aims to evaluate and analyze the linalool-zinc oxide nanocomposite (Lin-ZNP) for treating cystic echinococcosis. Lin-ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The protoscolicidal effects of Lin-ZNP were tested on hydatid cyst protoscoleces (PTS) in both in vitro and ex vivo by eosin exclusion test. The study also examined the impact on caspase-3 gene expression and the external structure of PTS. The in vivo effect was measured by examining hydatid cysts' quantity, dimensions, and weight in mice intraperitoneally infected with 0.5 mL of PTS solution containing 1,000 PTS. The antioxidant and inflammatory cytokine gene expression levels were examined using real-time PCR. Lin-ZNP significantly (P < 0.001) killed the PTS in both in vitro and ex vivo in a dose- and time-dependent manner. The treated PTS exhibited creases and protrusions as a result of bleb formation and upregulation in the gene expression of caspase-3. Upon treatment with Lin-ZNP, there was a significant (P < 0.001) reduction in the number, diameter, and weight of the hydatid cysts. Treatment with Lin-ZNP nanocomposite led to a significant increase in the expression of antioxidant genes and a notable decrease in oxidative stress markers, and the expression levels of IL-4 and IL-10. Lin-ZNP has the potential to act as a scolicidal agent and demonstrates promise in controlling hydatid cysts in a mouse model, attributed to its antioxidant and anti-inflammatory properties. However, additional studies in clinical trials are needed to confirm the use of Lin-ZNP for treating hydatidosis.

The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date: 30/03/2022).

Effectiveness of simulation-based clinical research curriculum for undergraduate medical students - a pre-post intervention study with external control

BackgroundSimulation is widely utilized in medical education. Exploring the effectiveness of high-fidelity simulation of clinical research within medical education may inform its integration into clinical research training curricula, finally cultivating physician-scientist development.MethodsStandard teaching scripts for both clinical trial and cross-sectional study simulation were designed. We recruited undergraduates majoring in clinical medicine at 3th grade into a pre-post intervention study. Additionally, a cross-sectional survey randomly selected medical undergraduates at 4th or 5th grade, medical students in master and doctor degree as external controls. Self-assessment scores of knowledge and practice were collected using a 5-point Likert scale. Changes in scores were tested by Wilcoxon signed-rank test and group comparisons were conducted by Dunn’s tests with multiple corrections. Multivariable quantile regressions were used to explore factors influencing the changes from baseline.ResultsSeventy-eight undergraduates involved the clinical trial simulation and reported improvement of 1.60 (95% CI, 1.48, 1.80, P < 0.001) in knowledge and 1.82 (95% CI, 1.64, 2.00, P < 0.001) in practice score. 83 undergraduates involved in the observational study simulation and reported improvement of 0.96 (95% CI, 0.79, 1.18, P < 0.001) in knowledge and 1.00 (95% CI, 0.79, 1.21, P < 0.001) in practice. All post-intervention scores were significantly higher than those of the three external control groups, P < 0.001. Higher agreement on the importance of clinical research were correlated with greater improvements in scores. Undergraduates in pre-post study showed high confidence in doing a future clinical research.ConclusionOur study provides evidence supporting the integration of simulation into clinical research curriculum for medical students. The importance of clinical research can be emphasized during training to enhance learning effect.

DReAmocracy: A Method to Capitalise on Prior Drug Discovery Efforts to Highlight Candidate Drugs for Repurposing.

In the area of drug research, several computational drug repurposing studies have highlighted candidate repurposed drugs, as well as clinical trial studies that have tested/are testing drugs in different phases. To the best of our knowledge, the aggregation of the proposed lists of drugs by previous studies has not been extensively exploited towards generating a dynamic reference matrix with enhanced resolution. To fill this knowledge gap, we performed weight-modulated majority voting of the modes of action, initial indications and targeted pathways of the drugs in a well-known repository, namely the Drug Repurposing Hub. Our method, DReAmocracy, exploits this pile of information and creates frequency tables and, finally, a disease suitability score for each drug from the selected library. As a testbed, we applied this method to a group of neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's disease and Multiple Sclerosis). A super-reference table with drug suitability scores has been created for all four neurodegenerative diseases and can be queried for any drug candidate against them. Top-scored drugs for Alzheimer's Disease include agomelatine, mirtazapine and vortioxetine; for Parkinson's Disease, they include apomorphine, pramipexole and lisuride; for Huntington's, they include chlorpromazine, fluphenazine and perphenazine; and for Multiple Sclerosis, they include zonisamide, disopyramide and priralfimide. Overall, DReAmocracy is a methodology that focuses on leveraging the existing drug-related experimental and/or computational knowledge rather than a predictive model for drug repurposing, offering a quantified aggregation of existing drug discovery results to (1) reveal trends in selected tracks of drug discovery research with increased resolution that includes modes of action, targeted pathways and initial indications for the investigated drugs and (2) score new candidate drugs for repurposing against a selected disease.

Preclinical and Clinical Studies on the Use of Extracellular Vesicles Derived from Mesenchymal Stem Cells in the Treatment of Chronic Wounds.

To date, the widespread implementation of therapeutic strategies for the treatment of chronic wounds, including debridement, infection control, and the use of grafts and various dressings, has been time-consuming and accompanied by many challenges, with definite success not yet achieved. Extensive studies on mesenchymal stem cells (MSCs) have led to suggestions for their use in treating various diseases. Given the existing barriers to utilizing such cells and numerous pieces of evidence indicating the crucial role of the paracrine signaling system in treatments involving MSCs, extracellular vesicles (EVs) derived from these cells have garnered significant attention in treating chronic wounds in recent years. This review begins with a general overview of current methods for chronic wound treatment, followed by an exploration of EV structure, biogenesis, extraction methods, and characterization. Subsequently, utilizing databases such as Google Scholar, PubMed, and ScienceDirect, we have explored the latest findings regarding the role of EVs in the healing of chronic wounds, particularly diabetic and burn wounds. In this context, the role and mode of action of these nanoparticles in healing chronic wounds through mechanisms such as oxygen level elevation, oxidative stress damage reduction, angiogenesis promotion, macrophage polarization assistance, etc., as well as the use of EVs as carriers for engineered nucleic acids, have been investigated. The upcoming challenges in translating EV-based treatments for healing chronic wounds, along with possible approaches to address these challenges, are discussed. Additionally, clinical trial studies in this field are also covered.

Long-term Effects of COVID-19 on Vascular Parameters—A Prospective Longitudinal Ultrasound Clinical Study

Objective: To investigate the longitudinal effects of COVID-19 on major vascular structures and parameters and clinical outcomes. Design: Observational prospective trial. Setting: Post-COVID-19 research clinic established by University of Louisville Division of Infectious Diseases. Participants: The study population consisted of 72 post-COVID-19 individuals and 11 non-COVID-19 infected participants in the control group. The participants were recruited from adult hospitals and from the community. The enrollment started in October 2020 and follow-up periods were at 3, 6, and 12 months from their initial COVID-19 diagnosis. Interventions: The participants were interviewed for medical and COVID-19 infection history. Samples of white blood cell (WBC), C-reactive protein (CRP), and D-dimer were taken at each visit. Certified sonographers performed vascular ultrasound on the study participants. Measurements and Main Results: Median intima-media thickness (IMT) was increased in mild/asymptomatic (0.80 mm) and severe/critical (0.90 mm) groups when compared with controls (0.60 mm; P &lt; .001 for both groups). In the asymptomatic/mild group, 6-month median IMT (0.88 mm) was increased, compared with the 3-month group (0.75 mm), with P = .026. Increased age was associated with decreased mean arterial blood velocities (cm/s): common carotid ( r = −0.236, P = .032), internal carotid ( r = −0.208, P = .048), and subclavian artery mean velocity ( r = −0.357, P = .003). We did not find any instance of deep vein thrombosis. Median D-dimer, CRP, and WBC in the control group differed from asymptomatic/mild COVID-19 group ( P = .026, .011, and .003, respectively). Moreover, WBC in the asymptomatic/mild group and moderate COVID-19 group differed from severe/critical group ( P = .025 and P = .027, respectively); CRP also differed between asymptomatic/mild group and severe/critical group ( P = .014). Conclusions: There were differences in intima-media lumen thickness (IMT), arterial velocities, and inflammatory markers in post-COVID-19 patients. There was no instance of deep vein thrombosis in this post-COVID-19 study cohort. The increased IMT might infer atherosclerosis, which has shown to increase cardiovascular risks. It is not yet known whether the increase in IMT due to COVID should be treated in the same way as non-COVID-19 atherosclerosis—through statins, for example—or whether regular cardiovascular risk reduction would be useful. Clinical trial and mechanistic studies should be performed to further our understanding of COVID-19-related vascular pathologies.

Post-marketing safety concerns with lumateperone: a pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database.

Lumateperone, a novel antipsychotic drug that was granted by the Food and Drug Administration (FDA) approval in December 2019, remains insufficiently explored for its adverse event profile. This study used the FDA Adverse Event Reporting System (FAERS) database to explore its potential safety issues. This study conducted a retrospective analysis of FAERS data from the fourth quarter of 2019 to the third quarter of 2023, extracting reports related to lumateperone. Disproportionality analysis using Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithms was employed to detect signals of adverse events (AEs). Our research processed 4,777 pertinent AE disclosures related to lumateperone, unveiling 125 signals that satisfied both ROR and BCPNN evaluative benchmarks across 26 System Organ Classes (SOCs). Intriguingly, 108 of these signals were categorized as unanticipated, spotlighting notable psychiatric manifestations such as mania (ROR = 73.82, 95% CI = 57.09-95.46; IC = 6.16, IC025 = 4.49), and hypomania (ROR = 34.74, 95% CI = 15.54-77.64; IC = 5.10, IC025 = 3.43), alongside non-psychiatric phenomena like urinary retention (ROR = 3.59, 95% CI = 1.80-7.19; IC = 1.84, IC025 = 0.18) and serotonin syndrome (ROR = 8.69, 95% CI = 4.81-15.72; IC = 3.11, IC025 = 1.45). This research provides real-world safety data on lumateperone post-marketing and is an important supplement to the information from clinical trial studies. Healthcare professionals should be vigilant for the risk of a manic switch in patients with bipolar depression who are administered lumateperone. More epidemiological studies are needed in the future to explore and further evaluate the risk-benefit issue of lumateperone.

The effect of web-based education on self-care behaviors in cardiovascular patients: application of the pender’s health promotion model

BackgroundCoronary artery disease is the most common cardiovascular disease, the mortality rate of which is increasing significantly. The most important way to prevent a second attack in patients undergoing angioplasty is self-care, which can be influenced by several factors such as the patient’s beliefs. Thus, the present study aimed to determine the effect of a web-based intervention based on the Pender’s health promotion model in patients with cardiovascular disease.MethodsThe present clinical trial study was conducted with 99 patients undergoing angioplasty treatment referring to Bushehr Heart Specialist Center. Random sampling was done and the participants were divided into two groups (50 subjects in intervention group and 49 subjects in control group). The data collection tool was a three-part questionnaire (including demographic information, a researcher-made questionnaire based on the health promotion model constructs, and self-care behaviors), which was completed in three stages (before, two weeks, and three months after the intervention). In addition to routine hospital services, the intervention group received multimedia training based on the constructs of the Pender’s health promotion model from the website. The control group received usual hospital services. Data were analyzed with chi-square, independent T-test and repeated measure ANOVA using SPSS-22 software.ResultsThe results showed that 2 weeks and 3 months after the intervention, the mean scores of perceived benefits, perceived self-efficacy and perceived social support had a significant increase in the intervention group compared to the control group, but the mean score of perceived barriers had a significant decrease in the intervention group (p < 0.001). Regarding self-care behaviors, after the intervention, the mean scores of self-care behaviors, physical activity, healthy diet, medication adherence and stress management had a significant increase in the intervention group compared to the control group (p < 0.001), but no significant was observed between the two groups in terms of changes in the non-smoking (p = 0.38).ConclusionThe results of the study showed that the web-based educational intervention based on the health promotion model is useful in improving the self-care behaviors of cardiac patients undergoing angioplasty. Nursing education and care have a great role in improving the self-care behaviors of cardiovascular patients.Trial registrationRegistration number: IRCT2017080635429N2. Registration date: 09/03/2017 (https://en.irct.ir/trial/26775).

Comparing the Efficacy of Inhaled Corticosteroid (ICS) Treatment in COPD Patients Based on Blood Eosinophilia: A Clinical Trial Study

Background: Inhaled corticosteroids (ICSs) have been widely used in the maintenance therapy of chronic obstructive pulmonary disease (COPD). Eosinophilic airway inflammation is a recognized inflammatory endotype in COPD. Nevertheless, the benefits and risks of ICS treatment remain controversial. Objectives: Therefore, in this study, we determine the frequency of eosinophilia in COPD patients and compare the effects of ICSs in patients with and without eosinophilia referring to the lung clinics of Zahedan University of Medical Sciences. Methods: In this study, 58 COPD patients were examined. Peripheral blood smears (PBS) were collected from all patients, and they were randomly divided into 2 groups. First, a 6-minute walking test (6MWT) was performed on all patients. Thereafter, two groups of patients received standard treatment with the Symbicort spray for 3 months. They were followed for this period, and the 6MWT was performed again at the end of the 3 months. Results: The mean results of the 6MWT test before and after intervention in the eosinophilia-positive group were 164.02 meters and 192.11 meters, respectively. Therefore, there was a significant difference in patient activity levels before and after ICSs (P = 0.017). In the eosinophilia-negative group, there was a significant difference in patient activity levels based on the 6MWT test before and after taking ICSs (P &lt; 0.001). However, there was no difference in activity levels between the two groups before and after the intervention (P = 0.68 and P = 0.36). Conclusions: Our finding showed that treatment with inhaled β2-agonists plus corticosteroids did not affect the response to this treatment in subjects' groups with and without eosinophilia compared to the pre-treatment conditions.

The application of neuronavigated rTMS of the supplementary motor area and rhythmic speech training for stuttering intervention.

Stuttering, a neurodevelopmental speech fluency disorder, is associated with intermittent disruptions of speech-motor control. Behavioural treatments for adults who stutter (AWS) concentrate on adopting speech patterns that enhance fluency, such as speaking rhythmically or prolonging speech sounds. However, maintaining these treatment benefits can be challenging. Neuroimaging studies suggest that supplementary motor area (SMA) which play a crucial role in speech initiation, planning and internal timing shows aberrant activation in speech production of AWS and may contribute to stuttering. Preliminary evidence suggests that brain stimulation may impact responsiveness to behavioural treatments. The present study aims to investigate whether excitatory repetitive transcranial magnetic stimulation (rTMS) of the SMA and rhythmic speech can consistently reduce stuttering severity across various measures. Ten self-identified Cantonese-speaking AWS participated in this double-blinded, sham-controlled clinical trial study (NCT05472181). The participants underwent 10 sessions of rhythmic speech training across two phases, combined with either neuronavigated rTMS or sham, with a 2-week washout period between phases. The stuttering severity was assessed through various outcome measures, including the percentage of syllables stuttered, self-perceived stuttering severity, and the brief version of Unhelpful Thoughts and Beliefs About Stuttering before and after each treatment phase. Results demonstrated improved speech fluency in various speaking contexts, with no significant difference between rTMS and sham conditions immediately and 1 week post-treatment. Notably, rTMS specifically led to less stuttering in tongue twister production (d = -0.70). Both treatment conditions effectively reduced self-perceived stuttering severity and negative thoughts and beliefs about stuttering. The findings of this study indicate that stimulating the SMA reduced stuttering, only in the production of tongue twisters that may require greater motor control and coordination. Furthermore, it indicates that rhythmic speech might help alleviate negative beliefs and anxiety related to stuttering. This research contributes to our understanding of neuromodulation in stuttering treatment and the role of the SMA in speech motor control and emphasises the need for more research on the potential benefits and limitations of applying rTMS in this condition. What is already known on the subject Behavioural treatments for adults who stutter concentrate on adopting speech patterns that enhance fluency, such as speaking rhythmically or prolonging speech sounds. However, maintaining these treatment benefits can be challenging. Neuroimaging studies indicate that aberrant neural activation in speech production regions, like the supplementary motor area (SMA), is involved in stuttering. The SMA plays a crucial role in initiating, planning, and sequencing motor behaviours. Preliminary evidence suggests that brain stimulation (e.g., transcranial direct current stimulation or transcranial magnetic stimulation) may impact responsiveness to behavioural treatments. What this paper adds to existing knowledge There is limited knowledge regarding the potential effects of stimulating the SMA to enhance speech fluency in people who stutter. Existing research primarily consists of single case studies that lack proper control conditions or involve only a single stimulation session. Due to their limited scope and power, these studies may not provide sufficient evidence. The current study expands upon existing research by investigating whether multiple sessions of repetitive transcranial magnetic stimulation over the SMA, combined with rhythmic speech, improve speech fluency in adults who stutter. Furthermore, it addresses the limitations of brain stimulation methods and proposes directions for future research. What are the potential or actual clinical implications of this work? This study implies that the stimulation of SMA reduced stuttering only in speaking contexts that may require greater motor control and coordination such as tongue twisters. Additionally, the research suggests that using rhythmic speech could potentially alleviate negative beliefs and anxiety associated with stuttering.

The Effect of Oral Gabapentin and Pregabalin as a Prodrug in Pain Control after Orthopedic Surgery on the Upper Limb: A Double-Blind Parallel Randomized Clinical Trial Study.

To compare the effects of oral gabapentin (GBP) and pregabalin (PGB) in pain control after orthopedic surgery on the upper limb. In this double-blind randomized clinical trial study, 80 patients who were the candidates for elective orthopedic surgery on one of the parts of the upper limb were divided into two groups using balance-block randomization. For the first group, a 150 mg capsule of PGB (one hour before the surgery) and for the second group, a 300 mg capsule of GBP (two hours before the surgery) were prescribed. Patients were subjected to standard monitoring at the beginning and during surgery. The pain scores were evaluated at before surgery, in PACU (postanesthesia care unit), and 6 and 12 hours after the surgery by VAS (visual analog scale). In this study, 37 subjects were allocated to each group. The participation rate was 92.5%. The mean with 95% confidence interval (CI) of pain scores over 4 times in the PGB group was 4.03 (3.25-4.79), 3.76 (3.02-4.49), 3.65 (3.06-4.23), and 3.41 (2.88-3.93) and in the GBP group was 4.08 (3.33-4.83), 2.78 (2.11-4.45), 2.3 (2.05-2.54), and 2 (1.51-2.50), respectively. The within-group comparisons showed a significant decrease in the pain score over time (P < 0.001). Also, the between-group comparison showed significant differences between the two groups in terms of pain score (P < 0.001). In the end, results showed that there is a significant interaction between time and intervention for pain score (P=0.042). Although two medicines led to a reduction in the pain score, but the rate reduction in the PGB group was significantly more than that in the GBP group. This trial is registered with IRCT20211013052759N1.

Evaluation of the Quality of Recovery from General Anesthesia in Dogs with Two Different Low Doses of Dexmedetomidine.

The purpose of this study was to evaluate the quality of recovery from general anesthesia with the administration of two low doses of dexmedetomidine in canine patients. For this blind randomized clinical trial study, 30 dogs undergoing general anesthesia for diagnostic procedures or elective surgery (ovariectomy/castration) were included. The patients were randomly divided into three groups, and at the end of anesthesia, they received a bolus of dexmedetomidine at 1 mcg/kg IV (D1), or a bolus of dexmedetomidine at 0.5 mcg/kg (D0.5), or a bolus of NaCl, in a total of 0.5 mL of solution for all three groups. After administration of the bolus, the anesthetist monitored the patients every 5 min by measuring heart rate, systolic and mean blood pressure, respiratory rate, and oxygen saturation. The quality of recovery was also assessed using 4 different scales. The extubation time, time of headlift, and standing position were also recorded. Both groups receiving dexmedetomidine had better awakening and a lower incidence of delirium when compared to saline administration. The heart rate was lower, while the systolic pressure was higher in the two groups D1 and D0.5 compared to the NaCl with a low presence of atrioventricular blocks. The extubation time resulted significantly higher in the D1 (17 ± 6 min) compared to the D0.5 (10 ± 4 min) and NaCl (8 ± 3 min) (p < 0.0001); the headlift time D1 (25 ± 10 min) resulted significantly longer than the NaCl group (11 ± 5 min) (p = 0.0023) but not than the D0.5 (18 ± 9 min). No significant differences were found among the three groups for standing positioning (D1 50 ± 18 min, D0.5 39 ± 22 min, NaCl 28 ± 17 min). The preventive administration of a bolus of dexmedetomidine at a dosage of 0.5 mcg/kg or 1 mcg/kg IV during the recovery phase improves the quality of recovery in patients undergoing general anesthesia.

Topical dexamethason effectiveness combined with surgical intervention in patients suffering from chronic subdural hematoma

BackgroundA chronic subdural hematoma (CSDH) is one of the most common neurosurgery operations. This study aimed to evaluate the effect of topical corticosteroids combined with surgery in patients with CSDH. Materials and MethodsThe present study is a clinical trial study on patients referred to hospitals associated with Ahvaz University of Medical Sciences with chronic subdural hematoma in 2019. Patients requiring surgical drainage of chronic subdural hematoma who met the inclusion criteria underwent open craniotomy surgery on the side of the hematoma. A drain was placed in the open craniotomy site. On the third day after the operation, before removing the drain, 40 mg of methylprednisolone sodium succinate was injected through the drain into the subdural space, after which the drain was pulled entirely. Patients were evaluated with the Markwalder Grading Scale (MGS) on the third day, third month, and sixth month after surgery for improved or worsened neurological symptoms. Also, in the third and sixth months after surgery, the patients underwent Computerized Tomography Scan imaging and were checked for recurrence. Results32 patients with CSDH entered the study, including 28 men and four women, with a mean age of 71.62 ± 9.85 years. Moreover, 87.5 % had a unilateral chronic subdural hematoma (uCSDH), and 12.5 % had a bilateral chronic subdural hematoma (bCSDH). Left and right uCSDHs had the same frequency (43. 8 %). After surgery, 26 patients had no postoperative complications, and six patients experienced pneumocephalus. ConclusionTopical dexamethasone injection through the potential CSDH cavity can result in desirable outcomes.

The Impact of Lingual Orthodontics on Gingival and Periodontal Health; A Systematic Review of Controlled Clinical Trial Studies.

Linguistic orthodontics is a highly successful and visually pleasing treatment method for addressing malocclusions. It possesses a multitude of advantages in addition to potential disadvantages, including speech impairments, mastication restrictions, and oral agitation. Lingual braces can cause gingival hyperplasia and impact the health of the gums and periodontal tissues. This study conducted a systematic review following the PRISMA standards, specifically examining lingual orthodontic treatments that were the subject of randomized controlled trials. The study found that lingual brackets are more advantageous than buccal brackets for flat surfaces. Both types of brackets have been found to be associated with an elevation in plaque retention, gingival irritation, and S. mutans count. Because of an increased demand for adult orthodontic care, there are designed discrete treatment options such as lingual bracket systems. The demand is largely driven by appearance and cosmetics. Apparently, lingual brackets proved to be more efficacious for the prevention of caries on flat surfaces. Additional research is necessary to gain a comprehensive understanding of lingual orthodontic efficacy and safety compared to its counterpart

Abstract PO5-25-07: A research impact assessment method to evaluate Susan G. Komen’s research funding impact on drugs approved for breast cancer treatment

Abstract Susan G. Komen (Komen) is the largest private funder of breast cancer research, having invested nearly $1.1 billion in cutting edge breast cancer research with a focus on conquering deadly metastatic and aggressive breast cancers, advancing precision medicine, and addressing disparities in breast cancer care and outcomes. There is a growing demand on Komen and other research funders from patients, donors, and other constituents to understand how investments in biomedical research translate into clinical impact that is meaningful to patients, the public, and others beyond academic publications and other bibliometrics. Komen uses a variety of approaches to evaluate the impact of our research investments, including a recently developed method to determine how Komen’s funding has impacted discovery and development of breast cancer drugs approved by the FDA from 2012-2022. Utilizing bibliometric analysis derived from the Dimensions for Funders platform, we systematically identified links between Komen-funded research, Komen-funded researchers, and FDA approved drugs. First, we identified fundamental clinical trials that led to initial and expanded FDA approval of each drug from prescribing information labels and press releases. Using API technology, we then performed a bibliometric linkage analysis and analyzed citation results from fundamental clinical trial studies, working backwards to capture fundamental pre-clinical and basic research studies that identified each drug’s target and its functions in the context of breast cancer biology. After collecting and curating publications in an unbiased manner, we evaluated each published study and contributing authors for Komen support. We identified specific “touchpoints” for fundamental studies including direct Komen funding for the published study and/or Komen support of key personnel. Early results revealed direct and indirect Komen research touchpoints across the research pipeline for several drugs, including direct touchpoints for basic, pre-clinical, and clinical trial studies that led to FDA approval of the PI3K inhibitor alpelisib, basic research and pre-clinical studies that led to FDA approval of CDK4/6 inhibitors, and basic research studies that led to FDA approval of PARP inhibitors olaparib and talazoparib. By adopting this approach, we can demonstrate the impact of Komen’s research investment across the full development timeline for each drug. This will allow us to measure and communicate how Komen’s investment in innovative research from discovery to clinical development is driving advances in breast cancer clinical care that improves outcomes. Citation Format: Dana Brantley-Sieders, Lauren Leslie, Amy Dworkin, Kimberly Sabelko, Kari Wojtanik. A research impact assessment method to evaluate Susan G. Komen’s research funding impact on drugs approved for breast cancer treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-07.

Abstract PO2-06-04: Prospective study on eribulin efficacy in advanced and metastatic breast cancer: changes in TGF-β compared to other standard chemotherapy agents (KBCSG-TR 2018, POTENTIAL)

Abstract Introduction Eribulin (E) has been demonstrated to improve overall survival (OS) compared to standard chemotherapies in pivotal phase III clinical trials (studies 301 and 305), although there was no difference in progression-free survival. These findings suggest that E might have a mechanism for OS improvement different from the common anti-tumor effect. Several studies reported that E inhibits epithelial-mesenchymal transition and the suppression of TGF-β plays a central role. Data on the relationship between the E-induced serial change in TGF-β and the improvement in OS remains insufficient. Therefore, we conducted this prospective observational study of patients treated with E while undergoing sequential TGF-β testing. This study also enrolled patients who received chemotherapy other than E as a control. Methods Patients with HER2-negative recurrent/metastatic breast cancer (MBC) were prospectively enrolled from 23 breast cancer centers in Japan, if they had not previously used E, had received two or fewer prior chemotherapy regimens, and were scheduled to start either E, capecitabine, S-1 or paclitaxel (± bevacizumab) between September 2020 and February 2022. The target sample sizes were 150 and 50 patients scheduled to receive E (Cohort E) and other drugs (Cohort Others), respectively. We collected blood samples for TGF-β testing at baseline, at two or three weeks (week 2/3), and at four or five weeks (week 4/5) from the beginning. The observation period was until February 2023. The primary endpoint was to evaluate the relationship between changes in TGF-β and clinical response, including OS and time to treatment failure (TTF). Results A total of 202 of the 203 enrolled patients were included in the analysis (1 patient declined consent). The median age was 60.0 (interquartile range, 52.0-69.0) years and ECOG performance status was 0 or 1 in all patients. Among 152 patients in Cohort E and 50 patients in Cohort Others, 37 patients (24.3%) and 12 patients (24.0%) had hormonal receptor-negative breast cancer, and 29 patients (19.1%) and 30 patients (60.0%) had no prior chemotherapy for MBC, respectively. Visceral metastasis totaled 115 (75.7%) in Cohort E and 46 (92.0%) in Cohort Others. In OS analysis of 199 patients, the median OS was 24.5 months (95% CI, 17.3-NA) for no prior chemotherapy, and 17.7 months for one or two prior chemotherapy (median follow-up 14.5 months). In Cohort E and Cohort Others, 139 and 45 patients, respectively, had paired samples for TGF-β testing at baseline and week 2/3. The proportion of patients with a percent change at week 2/3 from baseline in TGF-β (ΔTGF-β) of less than zero (decreased TGF-β) was 46.8% in Cohort E and 33.3% in Cohort Others, indicating a 13.4% (-2.6% – 29.5%) higher trend in Cohort E. Based on the time-dependent receiver operating characteristic (ROC) curves at 6 months for TTF, the threshold of ΔTGF-β was determined to be 27%. For the low ΔTGF-β group (&amp;lt; 27%) and the high ΔTGF-β group (≥27%), OS rates at median follow-up (14.5 months) were 70.6% and 54.3% (p=0.085) in Cohort E and 68.9% and 58.2% (p=0.585) in Cohort Others, respectively, suggesting a relationship between low ΔTGF-β and a favorable prognosis only in Cohort E. Conclusions The current study showed the trend in the higher frequency of decreased TGF-β, as well as the important relationship between decreased TGF-β and a favorable prognosis in patients treated with E compared with those receiving other chemotherapies. As the next step, further biomarker analyses including cytokines and chemokines, and immunological analyses are planned. Citation Format: Takahiro Nakayama, Tersuhiro Yoshinami, Fumie Fujisawa, Minako Nishio, Takashi Yamanaka, Toshinari Yamashita, Chiya Oshiro, Ayaka Izui, Nobumoto Tomioka, Hideki Maeda, Masafumi Shimoda, Kenzo Shimazu, Michiko Tsuneizumi, Ryoichi Matsunuma, Hiroko Bando, Aya Ueda, Hiroyuki Yasojima, Kumiko Okada, Kenichi Inoue, Yuichiro Kai, Katsuhide Yoshidome, Hidetoshi Kawaguchi, Masayuki Nagahashi, Kazuteru Oshima, Shinichiro Kashiwagi, Tsutomu Iwasa, Kanae Taruno, Shigeru Tsuyuki, Fumine Tsukamoto, Takashi Morimoto, Nobuyoshi Kittaka, Toru Higuchi, Yoichi Naito, Ryotaro Saita, Hiroyoshi Nishikawa, Daisuke Sugiyama, Yasuo Miyoshi, Yohei Uchida, Tomomi Yamada, Norikazu Masuda. Prospective study on eribulin efficacy in advanced and metastatic breast cancer: changes in TGF-β compared to other standard chemotherapy agents (KBCSG-TR 2018, POTENTIAL) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-04.

Regulatory Issues in Electronic Health Records for Adolescent HIV Research: Strategies and Lessons Learned.

Electronic health records (EHRs) are a cost-effective approach to provide the necessary foundations for clinical trial research. The ability to use EHRs in real-world clinical settings allows for pragmatic approaches to intervention studies with the emerging adult HIV population within these settings; however, the regulatory components related to the use of EHR data in multisite clinical trials poses unique challenges that researchers may find themselves unprepared to address, which may result in delays in study implementation and adversely impact study timelines, and risk noncompliance with established guidance. As part of the larger Adolescent Trials Network (ATN) for HIV/AIDS Interventions Protocol 162b (ATN 162b) study that evaluated clinical-level outcomes of an intervention including HIV treatment and pre-exposure prophylaxis services to improve retention within the emerging adult HIV population, the objective of this study is to highlight the regulatory process and challenges in the implementation of a multisite pragmatic trial using EHRs to assist future researchers conducting similar studies in navigating the often time-consuming regulatory process and ensure compliance with adherence to study timelines and compliance with institutional and sponsor guidelines. Eight sites were engaged in research activities, with 4 sites selected from participant recruitment venues as part of the ATN, who participated in the intervention and data extraction activities, and an additional 4 sites were engaged in data management and analysis. The ATN 162b protocol team worked with site personnel to establish the necessary regulatory infrastructure to collect EHR data to evaluate retention in care and viral suppression, as well as para-data on the intervention component to assess the feasibility and acceptability of the mobile health intervention. Methods to develop this infrastructure included site-specific training activities and the development of both institutional reliance and data use agreements. Due to variations in site-specific activities, and the associated regulatory implications, the study team used a phased approach with the data extraction sites as phase 1 and intervention sites as phase 2. This phased approach was intended to address the unique regulatory needs of all participating sites to ensure that all sites were properly onboarded and all regulatory components were in place. Across all sites, the regulatory process spanned 6 months for the 4 data extraction and intervention sites, and up to 10 months for the data management and analysis sites. The process for engaging in multisite clinical trial studies using EHR data is a multistep, collaborative effort that requires proper advanced planning from the proposal stage to adequately implement the necessary training and infrastructure. Planning, training, and understanding the various regulatory aspects, including the necessity of data use agreements, reliance agreements, external institutional review board review, and engagement with clinical sites, are foremost considerations to ensure successful implementation and adherence to pragmatic trial timelines and outcomes.

Comparison of the Effects of Govarcin Herbal Capsule and Metoclopramide for Alleviating Gastrointestinal Symptoms in Patients with Functional Dyspepsia: A Randomized Double-blind Clinical Trial.

Functional dyspepsia (FD) is felt as a discomfort or pain on the center line or upper abdomen. In this study, we aimed to compare the effects of Govarcin herbal capsule and Metoclopramide for alleviating gastrointestinal symptoms in patients with FD. Totally, 106 patients enrolled in a double-blind, clinical trial study. The participants had FD and were divided into two groups receiving Govarcin and Metoclopramide by block randomization. The patients were treated for four weeks, taking one Govarcin capsule or Metoclopramide tablet after each meal. The rate of improvement in patients was assessed by mitigation of clinical symptoms, including epigastric pain, fullness, discomfort, nausea, vomiting and heartburn. Also, before and after intervention, we used Nepin questionnaire and ROME III. SPSS statistics 25 software was used for data analyzing. Clinical symptom score changes between Govarcin and Metoclopramide patients' groups showed that there was no significant difference in any of the clinical symptom scores (except for heartburn, p-value=0.012) between the study groups. Nepean score in Govarcin group before and after treatment were 19.3±4.8 and 8.9±2.8, respectively (p-value<0.001). For Metoclopramide group, these values were 19.8±3.5 and 9.4±2.1 respectively (p-value<0.001). No significant difference was found in terms of Nepean score between the Govarcin and Metoclopramide groups (p-value=0.995). Govarcin herbal capsule can be used to remedy symptoms in patients with FD. It seems that Govarcin is as effective as Metoclopramide in fighting symptoms of FD as no significant difference in efficacy has been demonstrated between them.