Talas, Turkey

A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

Comparison Between Protraction Facemask and Upper Braces for Underbite Correction in Growing Children

1. Orthodontic assessment, consent and records taking All eligible patients identified at the Faculty of Dentistry, Universiti Malaya, will be scheduled for an orthodontic assessment during the research sessions. An explanation regarding the research objectives, interventions, randomization for treatment and details on protocols of each interventions will be given to the patient as written in the patient's information sheet. Patient will be reminded that they have to receive whatever treatment allocated to them with an open heart once they consented. Once patient agreed, further assessment will be done. If patient or parents not agree, their name will be put under waiting list for orthodontic treatment in this faculty. Following the extraoral and intraoral assessment, patient's parents or carer will have to sign a consent form. Then, study model impressions will be made using alginate Kromopan Type I Lascod, and bite registration will be done using modeling wax. Intraoral and extraoral photographs will be captured using a Canon EOS RP DSLR camera. Subsequently, appointments for dental panoramic tomography and lateral cephalometric radiography will be arranged at the X-ray Department, Faculty of Dentistry, Universiti Malaya. 2. Lateral cephalometric analysis In this study, Webceph Software Version 1.5.0 will be used for digital cephalometric analysis to assess skeletal and soft tissue of the patient. Soft copies of lateral cephalometric radiographs will be coded or named randomly by an individual assistant then uploaded to Webceph, and landmarks for skeletal and soft tissue analysis will be verified before conducting the analysis. All patients with ANB value equal to and less than 0 will be included in this study. 3. Interventions allocation All eligible patients will be randomized to determine their intervention as explained in 3.5.1. Further planning for their next appointment will be done as listed below 1. Intervention 1 - Protraction facemask Overjet, overbite, canine and molar relationship will be measured from the study model and recorded in a data collection form. Then, appointment will be given for impression taking to construct the Rapid Maxillary Expansion (RME). 2. Intervention 2 - Upper partial fixed appliance Overjet, overbite, canine and molar relationship will be measured from the study model and recorded in a data collection form. Then, an appointment for separators insertion will be arranged a week before appointment for the band and bond up procedures. 4. Treatment phase Before undergoing either intervention, all patients will need to complete the CPQ8-10. The instructions, as outlined on the front page of the questionnaire (see Appendix D and E), will be explained to the patients. They will be encouraged to reach out to the researcher (NFS) for clarification if any of the questions are unclear. This step will be repeated and patient has to fill in the same questionnaire every 3 months after treatment started. - T0 - before start treatment - 3 months after started treatment - 6 months after started treatment - 9 months after started treatment 5. Intervention 1 - PFM (protraction facemask) Patients assigned to intervention 1 will utilize the Petit protraction facemask from Dentamedik Sdn Bhd, in conjunction with a rapid maxillary expansion (RME). This facemask consists of a forehead pad and chin pad linked by a sturdy steel support rod. The RME will be affixed in the patient's mouth one week before activating the facemask, allowing the patient to adapt to the appliance. The design and components of the RME will adhere to standardized specifications An extraoral elastic band (Ormco Zoo Pack Elastics will be attached from the hook of the rapid maxillary expansion (RME) to the facemask rod, applying a forward force to the maxilla and ensuring the elastic crosses to prevent interference with the lips. The force vector is intended to pass through the maxilla center of resistance, and the point of force application should be distal to the lateral incisors, positioned in the canine-premolar area (Petit, 1983). The force position and direction should be inclined at an angle ranging from 20° to 30° to the occlusal plane (Petit, 1983). Patients will receive guidance to wear the Petit protraction facemask and elastics for 14-16 hours daily or as close to 24 hours as feasible (McNamara, 1987). The elastic force will be incrementally increased following the staggered approach proposed by Mandall in 2010. 6. Intervention 2 - UPFA Upper partial fixed appliance / 2 by 4 appliance (refer figure 3.7) will be used in this study by using bracket set (119-142 Unitek™ Gemini Bracket MBT™ U/L 5x5 0T-Cuspid 3Hk) with molar bands (3M™ Victory Series™ First Molar Bands) or buccal tubes (3M™ Victory Series™ Superior Fit Buccal Tubes) and upper nickel titanium archwires (3M™ Unitek™ Nitinol Heat-activated Archwire) and upper stainless steel archwires (3M™ Unitek™ Permachrome Standard Archwire) . The archwire sequence are listed below: 1. 016 nickel titanium archwire • To start with 014 nickel titanium as first archwire in a severely rotated cases 2. 018 stainless steel archwire A metal/plastic tubing will be used to protect the soft nickel titanium archwire and a niti push coil will be used on stainless steel archwire to jump the bite. A bite riser will be cemented (self-cured Glass Ionomer Orthodontic cement, GC Fuji Ortho) on lower posterior teeth to disengage the occlusion to allow anterior crossbite correction. 7. Follow up review Patients will be reviewed every six weeks until anterior crossbite is corrected. Post-treatment records will be taken, and the appliance will be debonded. No retainers will be given as positive overjet with incisal overlap is considered stable.

A Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan as the First-line Treatment for HER2-positive Gastric Cancer

The purpose of this study is to assess the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm. This study will be conducted at up to 200-250 sites globally in approximately 25 countries.

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

A Research Study Comparing How Well Different Doses of the Medicine NNC0519-0130 Can Reduce Kidney Damage in People Living With Chronic Kidney Disease

A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (NSCLC)

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line (1L) treatment for patients with squamous metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 (tumor cells (TC) ≥ 1%).

Preoperative Carbohydrate Drink in Adolescent Idiopathic Scoliosis Surgery: the Impact on Safety and Enhanced Recovery

Preoperative carbohydrate loading is strongly recommended by ESPEN as part of the clinical nutrition in surgery guideline. However, the implementation in clinical setup halted due to several limitations such as cost consuming, unfamiliar with new protocol and lack of expertise. Furthermore, there are no studies for preop carbohydrate loading in AIS as most preop carbohydrate loading is administered as a package for ERAS protocol. Thus, a strong level of evidence is necessary to propel a change in practice. As such, it is important to establish the relationship between carbohydrate loading before surgery and the impact on perioperative outcome. Understanding the potential benefits of this nutritional intervention in the adolescent scoliosis population could contribute to the ongoing efforts to optimize surgical care in these patients. Although preoperative carbohydrates loading has strong recommendation in spinal fusion ERAS protocol, the level of evident is still scarce, more so in idiopathic scoliosis. In a systematic review, it has also stated that its limitation as most of the literature is largely retrospective studies with non-randomised data and cohort studies lacking formal control groups (Gadiya et al., 2021). Moreover, evidence on other benefits for carbohydrates loading in scoliosis surgery is still lacking such as its impact on pain, return of bowel function and post op nausea and vomiting. This prospective study seeks to fill this knowledge gap by evaluating the influence of preoperative carbohydrate loading on postoperative outcomes in adolescents undergoing scoliosis surgery. We hypothesize that preoperative carbohydrate loading will be associated with an expedited return of bowel function, a reduced incidence of PONV, a shorter length of hospital stays, improvement in patient general wellbeing and no risk for aspiration. The objectives of this study are threefold. The primary goal of our study is to identify whether there is a significant improvement in the return of bowel function measured by flatus, reducing constipation by days of bowel opening and incidence of postoperative nausea and vomiting for patients receiving carbohydrate loading in comparison with patient that do not receive carbohydrate loading. Secondary objective also include carbohydrate loading and its effect on reducing length of hospital stay undergoing scoliosis surgery as well as patient overall condition in term of thirst, hunger and lethargy. The third objective is to measure the residual gastric volume using ultrasound before induction of anaesthesia.

cOncomitant Left Atrial aPpendage Closure and Pulsed Field ablaTION-Asia

The OPTION-A Study is an observational, prospective, single-arm, multi-center non-mandated post-market study. Subjects enrolled in the OPTION-A study will be clinically indicated for atrial fibrillation (AF) ablation procedure with the FARAPULSE PFA system and treatment with WATCHMAN LAAC Device, per physician's medical judgement and according to hospitals' standard of care. The objective(s) of the OPTION-A Study is to evaluate safety and effectiveness of catheter ablation with the FARAPULSE™ Pulsed Field Ablation (PFA) System and subsequent implant of Left Atrial Appendage closure (LAAC) with the WATCHMAN™ LAA Closure device in a concomitant procedure.

Volrustomig Priming Regimens Exploratory Phase II Platform Study

This is a platform, randomized, open-label, multicenter, global study. Enrolled participants with Stage IV non-squamous non-small cell lung cancer (NSQ NSCLC) who are treatment-naïve and have not received previous treatment for advanced or metastatic disease. These participants will be randomized in a 1:1 ratio to one of the two treatment arms: Arm 1A and Arm 1B. Both arms will test a volrustomig dosing in combination with chemotherapy.

A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery

Postoperative nausea and vomiting (PONV) remains a common adverse event after surgery and anaesthesia causing much dissatisfaction among patients. PONV incidence is reported at 30% in all surgical patients and up to 80% in high-risk patients. Idiopathic scoliosis is a common form of structural spinal deformities with a Cobb angle of >/ 10 degrees. It affects young females in the early pubertal stage more than young men by 1% and 4%. Posterior spinal fusion (PSF) surgery is commonly performed in patients with severe scoliosis. It is a long complex surgery inflicting extensive surgical field requiring opioids as the mainstay of analgesia during the perioperative period. These targeted population are particularly adolescent female requiring intraoperative and postoperative opioids who are at high risk of developing PONV. Dexamethasone and anti-serotonergic drugs like granisetron are commonly used antiemetics due to their efficacy and safety profiles. Dexamethasone is particularly favoured for its long duration of action and pain-reducing effects. Palonosetron, a second-generation anti-serotonergic drug, has a unique pharmacokinetic profile with a prolonged duration of action. It may be more beneficial for patients on prolonged opioid-based analgesic regimens. However, its higher cost and inconsistent study findings limit its widespread use, especially in scoliosis patients undergoing spinal fusion surgery. Total intravenous anaesthesia (TIVA) is recommended for high-risk PONV patients, as it reduces the emetogenic effect of volatile anaesthetics. Propofol, used in TIVA, is itself an effective antiemetic. TIVA with propofol has been shown to be as effective as giving a single antiemetic and can further reduce the risk of PONV when combined with other prophylactic antiemetics. The standard practice for managing PONV involves the administration of two antiemetics and considering TIVA for high-risk patients. This study aims to compare the effectiveness of palonosetron and ondansetron when administered alongside dexamethasone in scoliosis patients undergoing spinal fusion under TIVA. The study will also evaluate the number of rescue antiemetics needed, assess adverse effects, and measure patient satisfaction. The study will be randomized and double-blinded, to be conducted in University Malaya Medical Centre (UMMC). The sample size is calculated to be 92 participants, after taking into account a 20% dropout rate. Adult and adolescent idiopathic scoliosis patients undergoing PSF surgery will be eligible for the study. Written informed consent will be obtained from participants or their guardians, and assent will be obtained from adolescent participants. Patients will be randomized to receive either palonosetron or ondansetron along with dexamethasone. The study will follow standard anaesthetic techniques, including TIVA with remifentanil and propofol. Intravenous injections of the study drugs or placebo will be given during surgery, and dexamethasone will be administered as a baseline antiemetic. Morphine will be administered before the end of surgery for pain management.