Clinical Trial Study Research Articles

Cardiovascular handgrip responses during treadmill exercise: randomized pilot trial.

The isometric exercise performed using the handgrip (HG) acutely promotes elevation of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and in a non-consensual manner among articles elevation or maintenance of heart rate (HR). Currently, although there is a vast literature on the hemodynamic effects of interval training and isometric exercise with HG alone, there is still no consistent evidence of such adjustments occurring in the association between the two. Therefore, the objective of this study was to describe the acute hemodynamic responses found only during interval training and when combined with isometric contraction with HG. This is a pilot study of a crossover clinical trial. Seven male volunteers, aged 24±3.9 years, underwent three protocols on an ergometric treadmill, with a 3-minute warm-up at 30% of heart rate reserve (HRR), four sprints 2 minutes at 50% HRR and active intervals at the same speed as the warm-up. Randomization was carried out in a simple random manner. The protocols were classified according to the use of HG during sprints, as follows: PI = without HG; PII = HG 30% of handgrip strength (HGS) and PIII = 60% of HGS). Variations (Δ) in HR, double product (DP), SBP and DBP were evaluated. The presence of HG did not change HR behavior, but it increased DP (PI: 10,472±2,539 vs. PII: 12,217±1,933 vs. PIII: 13,369±3,089) through SBP, which in PI had a plateau behavior of 15±22.2 mmHg, while PII varied with an average of 41±12.2 mmHg and PIII 47±11.1 mmHg, in the 4th sprint. DBP fell in PI with 12±13.2 mmHg, while PII and PIII showed an drop of 0±19.6 and 6±13.0 mmHg in the last sprint, respectively. The use of HG during interval training directly modulates hemodynamic variables, promoting an increase in SBP elevation, attenuation of the drop in DBP and an increase in DP, without an increase in HR. RBR-78fhyrf. Available in https://ensaiosclinicos.gov.br/rg/RBR-78fhyrf.

Study Effect of Esomeprazole on the Treatment of Preeclampsia in Pregnant Women: A Double-Blind Clinical Trial Study

Background: Preeclampsia is one of the most serious complications of pregnancy, leading to various maternal and fetal complications. Objectives: This study aimed to determine the effect of oral esomeprazole in the treatment of preeclampsia in pregnant mothers. Methods: In this double-blind clinical trial, we compared oral esomeprazole with a placebo. The study population included 120 pregnant women with preeclampsia (60 in the esomeprazole 40 mg group and 60 in the placebo group) who were referred to Ba'ath Hospital in Sanandaj in 2023. Patient care and follow-up were conducted from the time of diagnosis of preeclampsia and inclusion in the study groups until delivery and the final condition of the baby. The outcomes investigated included prolongation of pregnancy and maternal, fetal, and neonatal outcomes. Results: The average delivery time in the esomeprazole group was 37.3 ± 1.2 weeks, compared to 37.5 ± 1.7 weeks in the placebo group, with no statistically significant difference (P = 0.75). The frequency of maternal outcomes, such as eclampsia, pulmonary edema, hemolysis, placental abruption, renal failure, hepatic hematoma, ascites, thromboembolism, and maternal death, was not statistically different between the esomeprazole and placebo groups, and no severe complications were observed in either group. Similarly, fetal outcomes, including intrauterine growth restriction (IUGR) and changes in fetal heart rate patterns, did not significantly differ between groups, with no instances of fetal or neonatal death observed. Additionally, neonatal outcomes, such as Apgar scores below 7, NICU admissions, mechanical ventilation, and other severe neonatal complications, were not significantly different between the two groups (P > 0.05). Although the esomeprazole group showed a lower frequency of adverse maternal, fetal, and neonatal outcomes compared to the placebo group, these differences were not statistically significant. Conclusions: The frequency of adverse maternal, fetal, and neonatal outcomes was lower in the esomeprazole group than in the placebo group for most variables, but the differences were not statistically significant. Therefore, it cannot be concluded with certainty that esomeprazole is ineffective in preventing or controlling preeclampsia.

Efficacy of Intraarticular Vancomycin in Preventing Infection in Patients Undergoing Hip Hemiarthroplasty

Background: Hip fractures are among the top ten causes of disability in adults worldwide. Patients with hip fracture are at significant risk of mortality and morbidity and reduced quality of life. This study was conducted with the aim of investigating the effect of intra-articular vancomycin in preventing infection in patients undergoing hip hemiarthroplasty. Materials and Methods: This double-blind controlled clinical trial study was conducted on 48 patients with femoral neck fracture candidates for hip hemiarthroplasty hemiarthroplasty in Orthopedic clinic of Golestan and Imam Khomeini Hospital, Ahvaz, Iran between June and November 2023. Eligible patients were divided into two equal groups. The intervention group received 1gram vancomycin intra-articularly during the operation before closure of fascia, and the control group did not receive vancomycin. The patients were followed up for 6 months after the operation, and the rate of superficial infection, periprosthetic joint infection (PJI) and wound complications were compared in two groups. The obtained data were statistically analyzed with IBM SPSS Statistics 21.0 for Windows. Results: The vancomycin group and the control group had no significant difference in the incidence of overall infection. The PJI in vancomycin and control groups were 4.16% and 8.33%, respectively. This difference was not statistically considerable (P=0.55). The results showed the incidence of superficial estimated 8.33% in vancomycin group and 4.16% in control group with no considerable difference in infection (P=0.52). Moreover, there was no meaningful difference in side effects between the two groups (P=0.63). There was no significant difference in wound complications between the two groups (P=0.3). . Conclusion: Intra-articular injection of 1gram of vancomycin suspension did not reduce the overall, superficial and deep infection after surgery. It is suggested that more clinical trial studies with higher sample size be conducted.

An Overview of Receptor-targeted Nanotechnological Approaches for the Treatment of Metastatic Breast Cancer

Abstract: Breast cancer (BC) is the second most prevalent cancer among women and can originate from the tubes, connective tissue, and lobules of the breast. The primary focus of this review is to highlight the significant advancement in the development of receptor-targeted nanotherapy for the management of metastatic breast cancer. These innovative systems directly target the specific cancer cell receptor to enhance the precision and effectiveness of the treatment. Inadequate therapy and incorrect diagnosis in conventional treatment have contributed to the rising mortality rate from breast cancer. BC that has spread to another organ in the body, commonly called Metastatic breast cancer (MBC) or Stage IV metastases, is an aggressive and heterogeneous illness that decreases the prognosis. The current treatment methods for MBC are similar to initial-stage breast cancer, which involve hormonal surgery, chemotherapy, immunotherapy, and radiation therapy with poor specificity and invasive. Moreover, treating MBC is more difficult because the cancer cells varies depending on the organ. Nanotechnology provides valuable insights for treating MBC that enable the early identification of tumor cells. Moreover, it can also transport therapeutic agents directly to the targeted sites while reducing the toxicity to healthy tissue. Due to its multifunctional, programmable, and trackable properties, future research and treatment may succeed with nanotechnology-based imaging and therapy. The present study summarizes an overview of nanotechnology-based drug delivery methods (NDDM) and receptor-targeting nanotherapy (RTN) that are applied in MBC therapy to gain attention in clinical applications. Clinical trial studies have also been discussed along with receptor-targeting nanomedicine and the status of the most relevant patent.

Tissue Plasminogen Activator or Perfluoropropane for Submacular Hemorrhage in Age-Related Macular Degeneration

Evidence is limited to support therapies to treat submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD) as an adjunct to anti-vascular endothelial growth factor therapy (anti-VEGF). To determine if intravitreal tissue plasminogen activator (TPA) or gas improves visual acuity or promotes resolution of SMH secondary to neovascular AMD in eyes treated with ranibizumab. This was a double-masked, sham-controlled, factorial randomized clinical trial and feasibility study that recruited participants from June 2014 to March 2019, with 12 months' follow-up. Included in the trial were patients from 4 UK vitreoretinal units who had fovea-involving SMH of at least 1 disc area secondary to neovascular AMD and were evaluated within 14 days of onset. Study eyes received baseline ranibizumab and were then randomized 2:1:1:1 to 1 of 4 intravitreal treatments: sham injection, perfluoropropane (C3F8), TPA, or combined C3F8 and TPA (C3F8 + TPA). All eyes received monthly pro re nata ranibizumab therapy over 12 months. Outcome assessors were masked to intervention assignment. Best-corrected visual acuity (BCVA) at month 3. Fifty-three of 56 participants (95%; mean [SD] age, 81.5 [8.1] years; 33 female [59%]) reached the primary end point. Study eyes were randomized to the following intravitreal treatments: sham injection (n = 23), C3F8 (n = 11), TPA (n = 11), or C3F8 + TPA (n = 11). On factorial analysis, the combined TPA groups had significantly better month 3 mean logMAR BCVA than those not receiving TPA: 0.66 vs 0.98 (μd = -0.32; 95% CI, -0.58 to -0.07; P = .02). There was no statistically significant difference comparing groups that did vs did not receive C3F8: 0.80 vs 0.90 (μd = -0.11; 95% CI, -0.37 to 0.16; P = .43). The combined TPA groups were less likely to have SMH present at month 1 (10 of 18 [55.6%] vs 21 of 24 [87.5%]; P = .03), a benefit not evident in the combined gas groups. The mean logMAR BCVA at 3 months was not significantly different between the groups: monotherapy control, 0.99; C3F8, 0.97 (vs control μd = -0.02; 95% CI, -0.48 to 0.44); TPA, 0.70 (vs control μd = -0.29; 95% CI, -0.79 to 0.21); combined C3F8 and TPA, 0.71 (vs control μd = -0.36; 95% CI, -0.82 to 0.11); P = .11. No safety differences were identified across the treatment groups. Results of this randomized clinical trial suggest that TPA may increase the chance of visual acuity gain when added to ranibizumab therapy for neovascular AMD in eyes with SMH, warranting consideration of additional clinical trials. ClinicalTrials.gov Identifier: NCT01835067.

Avelumab First-Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma: Results From the Real-World US PATRIOT-II Study

IntroductionIn JAVELIN Bladder 100, avelumab first-line maintenance (1LM) improved overall survival (OS) and progression-free survival (PFS) in patients with locally advanced/metastatic urothelial carcinoma (la/mUC) without progression following 1L platinum-based chemotherapy (PBC) versus best supportive care. PATRIOT-II describes real-world outcomes with avelumab 1LM. Patients and MethodsThis observational, retrospective study of avelumab 1LM in US community/academic centers used medical record data collected from avelumab initiation for ≥12 months to assess survival, safety, and healthcare resource utilization; analyses are descriptive. ResultsThe study included 160 patients from 37 centers (median age, 70 years; 77% male). Avelumab 1LM was initiated at a median of 4 weeks (IQR 3-6) after PBC completion. Median follow-up from avelumab 1LM was 16 months (IQR 11-21). At study end, 19.4% of patients continued avelumab; 73.7% had discontinued due to progression, adverse events (AEs), or performance status deterioration. Median PFS and OS from avelumab initiation were 5.4 months (95% CI, 3.8-6.9) and 24.4 months (95% CI, 20.4-28.4), respectively. Grade ≥3 treatment-related AEs (TRAEs) occurred in 15 patients (9.4%); 35 (21.9%) had any-grade immune-related AEs, and 23 (14.3%) received high-dose systemic corticosteroids for AEs. Forty-four patients (27.5%) were hospitalized during the avelumab treatment period, of whom 13 (8.1%) were hospitalized due to TRAEs. Limitations of this study include a small sample size, potential selection bias, and missing/unknown data. ConclusionThese results align with the JAVELIN Bladder 100 clinical trial and other real-world studies, supporting avelumab 1LM use in patients with la/mUC without progression following 1L PBC.

The effect of synbiotics in the treatment of drug-resistant epilepsy and the parental burden of caregivers: a single-arm pretest-posttest trial

BackgroundIn patients with drug-resistant epilepsy (DRE), the composition of the gut microbiome changes compared to drug-sensitive patients and healthy individuals. Synbiotics, a mixture of probiotics and prebiotics, aim to improve the balance of bacteria in the gut microbiome. This study aimed to assess the effect of synbiotics on the treatment of DRE and the burden on caregivers.MethodsThis one-group pretest-posttest quasi-experimental study was conducted in Arak, Iran. Thirty children with DRE, diagnosed by a pediatric neurologist and meeting the inclusion criteria in 2021-22, were included in the study. In addition to anticonvulsant drugs, infants were administered PediLact at a dose of 5–15 drops per day for eight weeks, and KidiLact at a dose of one sachet per day for eight weeks for children aged 2–15 years. Both PediLact and KidiLact are synbiotics. To investigate the burden on caregivers (parents), the Zarit Caregiver Burden Interview was conducted. In addition, the number of epileptic seizures was assessed from mothers before and immediately after the intervention over one month.ResultsThe mean age of the participants in the study was 8.6 years (SD: 3.4). Eighteen participants (60%) were boys, and 12 (40%) were girls. The results of the study showed a statistically significant decrease in the mean burden on caregivers, from 34.20 (SD: 14.4) before the intervention to 30.26 (SD: 15.8) after the intervention (P = 0.017). The mean frequency of seizures decreased significantly, from 15.83 (SD: 12.9) before the intervention to 12.73 (SD: 12.8) after the intervention (P = 0.001). Following the intervention, the seizure frequency stopped in two patients, decreased by 50% in six patients, increased in one patient, and remained unchanged in 21 patients.ConclusionThe results suggest that Symbiotics in DRE patients are associated with a lower parental burden of caregivers and seizure frequency. Well-designed randomized clinical trial studies are recommended to generate rigorous causal evidence and conclusions.

Research on therapeutic clinical trials including immunotherapy in triple-negative breast cancer: a bibliometric analysis.

Breast cancer, particularly triple-negative (TNBC), is a leading malignancy with aggressive traits and high metastasis rates. Clinical trial is an important tool for optimizing therapeutic strategies in the evaluation of the safety and efficacy for TNBC. Our bibliometric study of TNBC clinical trials aims to assess therapeutic strategies, identify trends, and explore advancements in treatment. We focus on mapping knowledge development, including key research entities and topics, and analyzing research trends and emerging methods. This analysis intends to inform future research, especially in personalized and precision medicine for TNBC. We selected publications on clinical trials for the treatment of TNBC from 1997 to 2024 in the Web of Science Core Collection (WoSCC). After an initial screening, we downloaded key data including titles, publication years, authors, countries, institutional affiliations, journals, keywords, and abstracts, and saved them in BibTex format. We then conducted a bibliometric analysis using Bibliometrix in R and VOSviewer to illustrate the prospects, highlights, and trends of TNBC treatment options. Furthermore, to emphasize the hot topics in TNBC treatment strategies, we performed a bibliometric analysis of immunotherapy using the same approach. 1907 publications were included, most of which were from China, Italy, and the United States. The number of annual publications has increased dramatically since 2010. The focus of TNBC clinical trial research has shifted from understanding the biology, such as breast cancer subtyping and genotyping, to novel therapeutic approaches. The major advancement in clinical trials is the switch from late-stage palliative treatment to early preoperative neoadjuvant therapy, as more TNBC cases are discovered at an early stage. Immunotherapy is also highlighted with additional alternatives for advanced or metastasized TNBC, such as targeted inhibitors with unusual mutation rates and antibody drug conjugates (ADC). This investigation made it apparent how immunotherapy has recently made major advancements in TNBC treatment plans and how ADCs, or targeted therapies, are currently popular for TNBC. By identifying significant papers, comprehending trending topics, and collaborating across multiple disciplines, this study may accelerate research on TNBC therapy options.

Role of oxidative stress in impaired type II diabetic bone repair: scope for antioxidant therapy intervention?

Impaired bone healing is a significant complication observed in individuals with type 2 diabetes mellitus (T2DM), leading to prolonged recovery, increased risk of complications, impaired quality of life, and increased risk of patient morbidity. Oxidative stress, resulting from an imbalance between the generation of reactive oxygen species (ROS) and cellular/tissue antioxidant defence mechanisms, has been identified as a critical contributor to the pathogenesis of impaired bone healing in T2DM. Antioxidants have shown promise in mitigating oxidative stress and promoting bone repair, particularly non-enzymic antioxidant entities. This comprehensive narrative review aims to explore the underlying mechanisms and intricate relationship between oxidative stress, impaired bone healing and T2DM, with a specific focus on the current preclinical and clinical evidence advocating the potential of antioxidant therapeutic interventions in improving bone healing outcomes in individuals with T2DM. From the ever-emerging evidence available, it is apparent that exogenously supplemented antioxidants, especially non-enzymic antioxidants, can ameliorate the detrimental effects of oxidative stress, inflammation, and impaired cellular function on bone healing processes during uncontrolled hyperglycaemia; and therefore, hold considerable promise as novel efficacious therapeutic entities. However, despite such conclusions, several important gaps in our knowledge remain to be addressed, including studies involving more sophisticated enzymic antioxidant-based delivery systems, further mechanistic studies into how these antioxidants exert their desirable reparative effects; and more extensive clinical trial studies into the optimisation of antioxidant therapy dosing, frequency, duration and their subsequent biodistribution and bioavailability. By enhancing our understanding of such crucial issues, we can fully exploit the oxidative stress-neutralising properties of these antioxidants to develop effective antioxidant interventions to mitigate impaired bone healing and reduce the associated complications in such T2DM patient populations.

Stress management training program to address caregiver burden and perceived stress among family caregivers of patients undergoing hemodialysis: a randomized controlled trial study

BackgroundThe objective of the current study was to assess the effectiveness of stress management training, grounded in Lazarus and Folkman’s stress management model, on reducing caregiving burden and perceived stress among family caregivers of patients on hemodialysis.MethodsThis two-group clinical trial study was conducted in parallel design among 60 family caregivers of patients on hemodialysis in 2023. The participants were divided into two groups of training and control using a random quadruple block allocation method. The intervention took place over two months, in six online group sessions of 35–45 min. Zarit Burden Inventory (ZBI) and Cohen’s Perceived Stress Scale (PSS-14) were used to collect information before and two weeks after the intervention. The study data were analyzed using and analysis of covariance (ANCOVA), pair, and independent t-tests at a significance level of 0.05.ResultsAt baseline, the two groups exhibited homogeneity in terms of mean scores for caregiving burden (Training group = 50.8 ± 4.9; Control group = 49.1 ± 6.0; P = 0.264) and perceived stress (Training group = 32.8 ± 4.7; Control group = 31.5 ± 2.4; P = 0.192). Nevertheless, following the intervention, there was a significant decrease in caregiving burden (Training group = 45.9 ± 4.1; Control group = 49.0 ± 5.8; P = 0.017) and perceived stress (Training group = 28.0 ± 4.4; Control group = 30.7 ± 3.5; P = 0.01) scores within the training group compared to the control group.ConclusionBased on the findings of the current study, given that family caregivers of patients on hemodialysis encounter psychological distress and contend with the negative aspects of care, it is advisable to implement psycho-educational interventions, such as stress management training. Incorporating these interventions into the care plan for hemodialysis could help mitigate these adverse consequences and provide valuable support for family caregivers.Trial registrationIranian Registry of Clinical Trials (IRCT), IRCT20180728040617N6. Registered on 17/04/2023.

Comparing the Effect of Granisetron with Meperidine on Post-Shivering in Elective Cesarean Section under Spinal Anesthesia

Background: Post-operative shivering after spinal anesthesia is a common issue in women undergoing cesarean section, then its management is necessary to increase patients’ satisfaction. Therefore, the current study aimed to compare the prophylactic effect of Granisetron and meperidine on post-spinal shivering in elective cesarean section. Methods: In this double-blinded clinical trial study, 100 women under elective cesarean section using block randomization were divided into two groups. The spinal anesthesia was performed in all women with 10 mg hyperbaric bupivacaine 0.5 %. Then, after the birth of the baby, the patients received 0.04 mg/kg Granisetron or 0.4 mg/kg meperidine intravenously. Mean Arterial Pressure (MAP), Heart Rate (HR), and percentage of arterial blood oxygen saturation (SpO2) were measured before intervention and 60 minutes after surgery using a standard monitoring device. Shivering was evaluated 30 minutes after the surgery in the recovery room according to the clinical examinations. Results: The changes in hemodynamics parameters were similar between the two groups. There was a statistically significant difference in the rate of shivering between the two groups. The rate of shivering in the Granisetron group was higher than in the meperidine group. Thus, 13 patients (26%) and 5 patients (10%) had shivering in the Granisetron and meperidine groups, respectively (p=0.037). Conclusion: Granisetron was not more effective than meperidine as routine treatment in preventing shivering after spinal anesthesia in women under elective cesarean section.

Double Ovarian Stimulation Versus Using Antagonist with a High Dose of Gonadotropin in Women with Poor Ovarian Response: A Randomized Clinical Trial Study

Background: Poor Ovarian Response (POR) to ovarian stimulation is a challenging factor in Assisted Reproduction Technology (ART). This study aimed to compare the efficacy of a conventional antagonist with high doses of gonadotropin protocol with double stimulation protocol in females with POR. Methods: This randomized clinical trial study was conducted on 60 women aged >35 with PORS at the Avicenna Infertility Center, Tehran, Iran. The participants were randomly divided into 2 groups (n=30 /each). In group 1, from the second day of the menstrual cycle, gonadotropin started at a dose of 450-600 units. In group 2, the second day of the menstrual period began with Letrozole 5 mg every night and an oral tablet of Clomiphene citrate 50 mg every day, and from the fourth day started 150 units of gonadotrophin (Triptorelin, 0.2 mg). Results: In this study, at the end of the follicular phase, there was a significant correlation between protocol type and the number of Germinal Vesicles (GV) (p=0.04). The mean number of oocytes retrieved was 2.76±1.9 in the conventional method and 3.23±2.1 in the double stimulation group (p=0.90). The number of fertilized oocytes was 31 in the conventional protocol and 25 in the double stimulation protocol. The mean number of pregnancies that led to the fetus was 1.38±1.3 in the conventional protocol and 0.96±0.9 in the double stimulation group (p=0.018). Conclusion: The results of this study show that the embryos in the double-stimulation group were more capable of completing the pregnancy, and the double-stimulation group had a higher live birth rate.

Harm effects in non-registered versus registered randomized controlled trials of medications: a retrospective cohort study of clinical trials

BackgroundTrial registration aims to address potential bias from selective or non-reporting of findings, and therefore has a vital role in promoting transparency and accountability of clinical research. In this study, we aim to investigate the influence of trial registration on estimated harm effects in randomized controlled trials of medication interventions.MethodsWe searched PubMed for systematic reviews and meta-analyses of randomized trials on medication harms indexed between January 1, 2015, and January 1, 2020. To be included in the analyses, eligible meta-analyses should have at least five randomized trials with distinct registration statuses (i.e., prospectively registered, retrospectively registered, and non-registered) and 2 by 2 table data for adverse events for each trial. To control for potential confounding, trials in each meta-analysis were analyzed within confounder-harmonized groups (e.g., dosage) identified using the Directed Acyclic Graph method. The harm estimates arising from the trials with different registration statuses were compared within the confounder-harmonized groups using hierarchical linear regression. Results are shown as ratio of odds ratio (OR) and 95% confidence interval (CI).ResultsThe dataset consists of 629 meta-analyses of harms with 10,069 trials. Of these trials, 74.3% were registered, and 23.9% were not registered, and for those registered, 70.6% were prospectively registered, while 26.3% were retrospectively registered. In comparison to prospectively registered trials, both non-registered trials (ratio of OR = 0.82, 95%CI 0.68 to 0.98, P = 0.03) and retrospectively registered trials (ratio of OR = 0.75, 95%CI 0.66 to 0.86, P < 0.01) had lower OR for harms based on 69 and 126 confounders-harmonized groups. The OR of harms did not differ between retrospectively registered and non-registered trials (ratio of OR = 1.02, 95%CI 0.85 to 1.23, P = 0.83) based on 76 confounders-harmonized groups.ConclusionsMedication-related harms may be understated in non-registered trials, and there was no obvious evidence that retrospective registration had a demonstrable benefit in reducing such selective or absent reporting. Prospective registration is highly recommended for future trials.

Silent brain ischemia within the TAXINOMISIS framework: association with clinical and advanced ultrasound metrics.

IntroductionThe relationship between carotid artery stenosis (CAS) and ipsilateral silent brain ischemia (SBI) remains unclear, with uncertain therapeutic implications. The present study, part of the TAXINOMISIS project (nr. 755,320), aimed to investigate SBIs in patients with asymptomatic CAS, correlating them with clinical, carotid ultrasonographic data, and CFD analyses.MethodsThe TAXINOMISIS clinical trial study (nr. NCT03495830) involved six vascular surgery centers across Europe, enrolling patients with asymptomatic and symptomatic CAS ranging from 50 to 99%. Patients underwent carotid ultrasound and magnetic resonance imaging (MRI), including brain diffusion-weighted, T2-weighted/FLAIR, and T1-weighted sequences. Brain MRI scans were analyzed for the presence of SBI according to established definitions. Ultrasound assessments included Doppler and CFD analysis. Only asymptomatic patients were included in this substudy.ResultsAmong 195 asymptomatic patients, the mean stenosis (NASCET) was 64.1%. Of these, a total of 33 patients (16.9%) had at least one SBI detected on a brain MRI scan. Specifically, 19 out of 33 patients (57.6%) had cortical infarcts, 4 out of 33 patients (12.1%) had ipsilateral lacunar infarcts, 6 out of 33 patients had (18.2%) subcortical infarcts, 1 out of 33 patients (3.0%) had both cortical and lacunar infarcts, and 3 out of 33 patients (9.1%) both cortical and subcortical infarcts. Patients with SBIs exhibited significantly higher risk factors, including a higher body mass index (28.52 ± 9.38 vs. 26.39 ± 3.35, p = 0.02), diastolic blood pressure (80.87 ± 15.73 mmHg vs. 80.06 ± 8.49 mmHg, p = 0.02), creatinine levels (93.66 ± 34.61 μmol/L vs. 84.69 ± 23.67 μmol/L, p = 0.02), and blood triglycerides (1.8 ± 1.06 mmol/L vs. 1.48 ± 0.78 mmol/L, p = 0.03). They also had a higher prevalence of cardiovascular interventions (29.6% vs. 13.8%, p = 0.04), greater usage of third/fourth-line antihypertensive treatment (50%vs16%, p = 0.03), and anticoagulant medications (60% vs. 16%, p = 0.01). Additionally, the number of contralateral cerebral infarcts was higher in patients with SBIs (35.5% vs. 13.4%, p &amp;lt; 0.01). Moreover, carotid ultrasound revealed higher Saint Mary’s ratios (15.33 ± 12.45 vs. 12.96 ± 7.99, p = 0.02), and CFD analysis demonstrated larger areas of low wall shear stress (WSS) (0.0004 ± 0.0004 m2 vs. 0.0002 ± 0.0002 m2, p &amp;lt; 0.01).ConclusionThe TAXINOMISIS clinical trial provides valuable insights into the prevalence and risk factors associated with SBIs in patients with moderate asymptomatic carotid stenosis. The findings suggest that specific hemodynamic and arterial wall characteristics may contribute to the development of silent brain infarcts.

Exploring the Efficacy of Convalescent Plasma Therapy in COVID-19 Patients: A Clinical Trial Study

Background: In December 2019, a group of patients in Wuhan, Hubei province, China, presented with severe illness and pneumonia of unknown origin. Subsequently, a novel coronavirus was identified as the cause and named "2019 novel coronavirus" (2019-nCoV), later defined as "SARS-CoV-2" (Severe Acute Respiratory Syndrome Coronavirus-2), leading to the development of the disease known as COVID-19. This study aimed to evaluate the effectiveness and safety of convalescent plasma as a potential therapy for patients with COVID-19. Methods: Patients diagnosed with COVID-19 based on real-time polymerase chain reaction (PCR) or CT-Scan symptoms were randomly assigned to either the treatment group (n = 29, received convalescent plasma) or the control group (n = 29). Clinical manifestations and pulmonary involvement were monitored three times during the study. At the end of the intervention, patients were evaluated for clinical symptoms, laboratory test results, and length of hospital stay. Results: Among the 58 patients who completed the study, there were no significant differences in baseline characteristics between the treatment and control groups upon admission to the hospital. However, the length of hospital stay was significantly shorter (9.54 days) in the convalescent plasma group compared to the control group (12.88 days). Conclusion: The findings from this study indicate that the use of convalescent plasma therapy, in addition to standard treatment, did not result in reduced mortality or improved clinical outcomes at day 7 when compared to a placebo or control group.

Post-trial access practice in malaria, tuberculosis, and NTDs clinical trial studies in Sub-Saharan African countries, quantitative study

Background According to CIOMS, 2016 post-trial access (PTA) refers to the ethical imperative that requires the sponsor, researchers, and relevant public health authority, "to make available as soon as possible any intervention or product developed, and knowledge generated, for the population or community in which the research is carried out." PTA is stipulated and recommended by different international research guidelines like CIOMS, and it was acknowledged that PTA should be accessible to those who actively participated in the trial study and the community and/or host country. Law, policy, and practical guidance for PTA has so far been vague but has recently attracted and increased attention in the context of benefit sharing of scientific research results with low- and middle-income countries (LMICs). Even though the number of clinical trials conducted in the Sub-Saharan countries has increased in the past two decades, PTA plan and practice is underreported or very low. Objective to evaluate PTA plan and implementation practice on TB, Malaria and NTD clinical trial studies conducted in the sub-Saharan African countries. Method a quantitative, cross sectional study survey approach is used to evaluate the PTA plan and practice of PI, trial coordinators, and sponsors in Sub-Saharan African countries. Finding misunderstanding of the term PTA, lack of plan, discussion, and arrangement on PTA between research stakeholders. Conclusion PTA training should be prepared and facilitated for researchers, IRB members, PIs, funders, and sponsors; discussion and arrangement on PTA should be done before the conduct of the trial; and there should be written agreement between the parties to guarantee PTA to study participants and community after the end of the trial study.

Effects of a Long-Term Supervised Schroth Exercise Program on the Severity of Scoliosis and Quality of Life in Individuals with Adolescent Idiopathic Scoliosis: A Randomized Clinical Trial Study.

Background and Objectives: Adolescent Idiopathic Scoliosis (AIS) affects individuals aged 10-18 years and is characterized by spinal deformity, three-dimensional axis deformation, and vertebral rotation. Schroth method exercises and braces have been shown to reduce the Cobb angle and halt spinal deformity progression. The aim of this study was to investigate the impact of a 12-month, supervised Schroth exercise program on scoliosis severity and quality of life in adolescents with AIS. Materials and Methods: Eighty adolescents with AIS (aged 10-17 years) were prescribed a brace and were divided into two groups. The intervention group followed a supervised Schroth exercise program three times a week for 12 months in addition to wearing a brace. The control group used only the brace. Outcomes included the Cobb angle of the main curvature and the sum of curves using radiography, the maximum angle of trunk rotation (ATR maximum, using a scoliometer), and quality of life with the Scoliosis Research Society-22 (SRS-22) questionnaire. Evaluations were conducted at baseline, after 12 months, and 6 months post-intervention. A multivariate analysis of covariance (MANCOVA) was used for statistical analysis (p-Value < 0.05). Results: The intervention group showed statistically significant improvement compared to the control group in the 12th month in Cobb angle (mean differences, 95% CI: -3.65 (-5.81, -1.53), p-Value < 0.001, Cohen's d = 0.30), ATR maximum (mean differences, 95% CI: -3.05 (-3.86, -2.23), p-Value < 0.001, Cohen's d = 0.74), and SRS-22 score (mean differences, 95% CI: 0.87 (0.60, 1.13), p-Value < 0.001, Cohen's d = 0.58). Differences in ATR maximum and SRS-22 score remained significant at the 18-month measurement. No significant differences were found between groups in the sum of curves (p-Value > 0.05). Conclusions: A 12-month supervised Schroth exercise program in AIS patients undergoing brace treatment significantly improves scoliosis severity (Cobb angle and ATR maximum) and quality of life. Improvements were greater than those in shorter-duration studies, suggesting a linear dose-response relationship. Further clinical studies are needed to clarify the impact of long-term Schroth programs.

Personalised High Tibial Osteotomy Surgery Is Accurate: An Assessment Using 3D Distance Mapping

Early-stage knee osteoarthritis is often suitable for treatment with high tibial osteotomy (HTO). This is an effective joint-preserving treatment, resulting in good postoperative outcomes. To overcome the limitations of traditional HTO, the surgical technique and correction accuracy can be enhanced by personalised procedures using three-dimensional digital planning and metal additive manufacturing, The purpose of this clinical trial study was to evaluate the three-dimensional accuracy of a new personalised HTO procedure, using modern imaging techniques, 3D modelling, and distance map analysis (DMA). Twenty-five patients were treated with the personalised HTO procedure. Before surgery and after 6 months, they underwent clinical evaluation scoring, radiographic imaging, and computed-tomography scanning to generate morphological models. Specifically, preoperative tibia models were used to plan the tibia correction and the design and position of the fixation plate. Preoperative, planned, and postoperative models were imported in computer-aided and designing software (Geomagic ControlTM 2014, 3D Systems, Rock Hill, SC, USA) for DMA implementation to assess geometrical differences between model surfaces. A very good reproduction of the planned tibia morphology was achieved postoperatively (average differences between −0.9 mm and 1.4 mm). DMA values associated with fixation-plate deformation were less than 1 mm, similar to those for plate-to-tibia surface-contour matching. Overall, personalised digitally planned HTO utilising three-dimensional printed surgical guides and plates enables accurate planned correction and plate placement.

Low serum glycine strengthens the association between branched-chain amino acids and impaired insulin sensitivity assessed before and after weight loss in a population with pre-diabetes: The PREVIEW_NZ cohort

AimAccumulation of circulating branched-chain amino acids (BCAA) is a hallmark feature of impaired insulin sensitivity. As intracellular BCAA catabolism is dependent on glycine availability, we hypothesised that the concurrent measurement of circulating glycine and BCAA may yield a stronger association with markers of insulin sensitivity than either BCAA or glycine alone. This study therefore examined the correlative relationships of BCAA, BCAA and glycine together, plus glycine alone on insulin sensitivity-related markers before and after an 8-week low energy diet (LED) intervention. MethodsThis is a secondary analysis of the PREVIEW (PREVention of diabetes through lifestyle Intervention in Europe and Worldwide) Study sub-cohort. Eligible participants with pre-diabetes at baseline who achieved ≥8% body weight loss following an LED intervention were included, of which 167 paired (Week 0 and Week 8) blood samples were available for amino acid analysis. Glycemic and other data were retrieved from the PREVIEW consortium database. Repeated measures linear mixed models were used to test the association between amino acids and insulin sensitivity-related markers (HOMA2-IR, glucose, insulin, and C-peptide). ResultsElevated BCAA was associated with impaired insulin sensitivity (p < 0.05), with strength of association (ηp2) almost doubled when glycine was added to the model. However, glycine in isolation was not associated with insulin sensitivity-related markers. The magnitude (β-estimates) of positive association between BCAA and HOMA2-IR, and inverse association between glycine and HOMA2-IR, increased when body weight was higher (Body weight*BCAA, Body weight*glycine, p < 0.05, both). ConclusionLow serum glycine strengthened the association between BCAA and impaired insulin sensitivity. Given that glycine is necessary to facilitate intracellular BCAA catabolism, measurement of glycine is necessary to complement BCAA analysis to comprehensively understand the contribution of amino acid metabolism in insulin sensitivity. Clinical Trial RegistrationThis study was registered with ClinicalTrials.gov (NCT01777893).

Investigating the effect of adding silymarin to the standard treatment of naloxone in methadone intoxication; a double-blind clinical trial

Introduction: In cases of methadone intoxication, the drug is mainly processed by the liver, however, its elimination through the kidneys is also crucial. On the other hand, naloxone therapy is a gold standard treatment for opioid intoxication, the addition of other drugs can improve its benefits and reduce side effects. Objectives: This study aimed to assess the effectiveness of adding silymarin to the standard treatment of naloxone in patients with methadone intoxication, to improve patient outcomes and reduce the risk of complications associated with alone naloxone therapy. Patients and Methods: This clinical trial study aimed to investigate the efficacy of silymarin in combination with standard treatment for methadone intoxication patients. The study employed a control group, which received standard treatment with naloxone, and an intervention group, which received both naloxone and silymarin. Liver functional tests (LFTs), kidney functional tests, malondialdehyde (MDA), and ferric-reducing ability of plasma (FRAP) were measured at admission and post-intervention times to compare the outcomes between the two groups. Statistical analyses, including chi-square, independent and paired t tests, Wilcoxon, and Mann-Whitney tests were conducted to identify significant differences between the groups. Results: Results indicated that 32 and 33 patients were included in the naloxone and naloxone + silymarin groups, respectively. The results showed that the changes in kidney functional tests such as blood urea nitrogen (BUN) and creatinine (Cr), MDA, and FRAP were not statistically significant between the two groups. However, the changes in LFTs, including, aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), were statistically significant. Notably, the LFT changes were more pronounced in the group receiving both naloxone and silymarin, indicating a greater reduction in liver enzymes in this combined treatment group. Conclusion: The addition of silymarin to standard naloxone treatment for methadone intoxication patients could improve liver function, as the combined therapy showed a more pronounced reduction in liver enzyme levels compared to standard treatment alone; however, this combination treatment could not change the kidney function and oxidative stress markers. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20210216050377N1; ethical code from Shahrekord University of Medical Sciences; IR.SKUMS.REC.1400.048). This study was also registered in Research Registry website with Unique Identifying Number (UIN) of researchregistry10395.