Windsor Park Kraaifontein, South Africa

Acute Effects of Isoenergetic HIIE Vs. MICE on Key Parameters of Fat Mass Loss in Young Females with Overweight or Obesity

Bridging the Healing Gap: A Single-Blind Clinical Trial Assessing the Efficacy of Carboxy-gel in Reducing Bruising and Pain Post-Liposuction

Study Design: Randomized, controlled, single-blind trial - Allocation: Randomized (one area with CO2 lift treatment, one area with Vaseline control) - Intervention Model: Comparative contralateral randomized clinical trial (each participant serves as their own control, with CO2 lift applied to one area and Vaseline to the contralateral area). - Masking: Single-blind (Participants are blinded to the treatment allocation). Study Locations: - Dhara Clinic, Bogota, Colombia - Private Practice, Sao Paulo, Brazil - Private Practice, Mexico City, Mexico Data Collection: - Photographic analysis with ImageJ, from photo records from days 1, 3, 7 post procedure, to calculate the percentage of the area with ecchymosis. - Pain Assessment: Visual Analogue Scale (VAS) scores recorded at the same time points. - Satisfaction Scores: Global Aesthetic Improvement Scale (GAIS) evaluated at least 3 months postoperatively. Ethical Considerations: - Informed Consent: Participants will be provided comprehensive information about study procedures, risks, and benefits, and written consent will be obtained. - IRB Approval: The study will adhere to the Declaration of Helsinki principles and will be approved by an Institutional Review Board (IRB). - Data Confidentiality: All participant data will be anonymized and securely stored.

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.

SEALion: Study on Supplemental Oxygenation Via Nasal Cannula for Young Children During Intubation

Eligible children will undergo preparation for intubation following the local Standard Operating Procedures (SOPs) of the pediatric anesthesia departments. Mandatory monitoring includes pulse oximetry (SpO2), heart rate (HR), and non-invasive blood pressure (NIBP). Anesthesia Induction: Where feasible, all children enrolled in this protocol will be pre-oxygenated for one minute prior to induction of anesthesia using a face mask with FiO2 1.0 and a flow rate of 6-10 L/min. Anesthesia induction for tracheal intubation will involve a combination of sedative or hypnotic drugs, opioids, and a non-depolarizing muscle relaxant. Required Medications (per protocol): Neuromuscular Blocking Agent (NMBA): One of the following-Rocuronium 0.5-1 mg/kg, Cis-Atracurium 0.2-0.5 mg/kg, Atracurium 0.5 mg/kg, Vecuronium 0.1 mg/kg, Mivacurium 0.2-0.3 mg/kg, or Succinylcholine 2 mg/kg. Hypnotic Agent: One or more of the following-Thiopentone 4-7 mg/kg, Ketamine 0.5-2 mg/kg, Propofol 1-4 mg/kg, Midazolam 0.5-1 mg/kg, or Sevoflurane up to 8%. Optional Medications: An opioid and/or anticholinergic may be administered at the anesthetist's discretion. Pre-Intubation Preparation: Following induction of anesthesia and administration of an NMBA, bag-mask ventilation with FiO2 1.0 (flow rate of 6-10 L/min) will be performed for 60 seconds until apnea occurs. To facilitate airway management, complete neuromuscular blockade will be confirmed using train-of-four (TOF) monitoring. Oxygen administration, laryngoscopy, and tracheal intubation will follow. Intubation Procedure: Oxygen administration during intubation is mandatory for all participants and will be randomized as follows: Apneic Oxygenation: Oxygen will be administered at 1 L/kg/min via a conventional nasal cannula. Laryngoscopy and tracheal intubation will proceed following apneic oxygenation. Standard Care: No apneic oxygenation will be administered. After induction, laryngoscopy and tracheal intubation will proceed without additional oxygen support. Tube Selection: For premature neonates under 1 kg, an uncuffed tube with an internal diameter (ID) of 2.5 will be used. For premature neonates and newborns between 1 kg and 3.0 kg, an uncuffed tube with ID 3.0 will be used. For babies over 3.0 kg up to 8 months, a cuffed tube with ID 3.0 or an uncuffed tube with ID 3.5 will be used. For infants aged 8 to 12 months, a cuffed tube with ID 3.5 or an uncuffed tube with ID 4.0 will be used. Oxygen delivery will follow the assigned randomization group, either via conventional nasal cannula (apneic oxygenation) or standard care. Laryngoscope Blade Selection: For children weighing less than 1 kg, a Miller or Macintosh blade, size No. 0, will be used. In cases of unexpected difficult intubation, the difficult airway algorithm will be applied. After an unsuccessful first intubation attempt with the assigned flow rate, clinical judgment will guide the intubating physician on whether to repeat the attempt with the same flow rate or to modify the flow rate, blade size, or type of laryngoscope. A maximum of four intubation attempts will be allowed, with the final attempt performed by the most experienced physician present. Additional tools, such as a stylet or bougie, may be used at any stage. If intubation remains unsuccessful, the difficult airway algorithm will be applied, and a supraglottic airway (SGA) device will be inserted.

Brazilian Registry of Chronic Venous Disease - Risk Factors, Comorbidities, Clinical and Surgical Treatment

Chronic venous disease (CVD), also known as chronic venous insufficiency in its advanced stages, is marked by dysfunction in the peripheral venous system of the lower extremities, often due to venous flow obstruction or reflux. Affecting approximately 25-45% of women and 10-40% of men, CVD significantly increases public health expenditures. While the exact mechanisms remain unclear, evidence suggests that CVD is multifactorial, involving heightened inflammation, valvular incompetence, and calf muscle dysfunction, all contributing to impaired venous return and elevated venous pressure. Common symptoms include varicose veins, lower limb edema, leg discomfort, and heaviness. CVD is progressive and can advance from superficial vessel involvement, known as telangiectasia, to deep venous ulcers. Risk factors such as family history, prolonged standing, smoking, and obesity can contribute to its onset and progression. Conservative management focuses on lifestyle changes like exercise, weight control, limb elevation, and compression. Pharmacologic or surgical intervention may be necessary in advanced cases. Left untreated, CVD can severely impact patients' quality of life, hindering daily and work activities. However, data on CVD prevalence in Brazil is limited, largely based on a single study by Maffei et al. in 1986, which found a 47.6% prevalence of varicose veins and a 3.6% prevalence of advanced CVD in 1,755 adults in Botucatu, São Paulo. To better serve Brazilian patients, further data on CVD prevalence, treatment, and risk factors is essential, aiding healthcare providers in optimizing patient care. This study aims to characterize the clinical and epidemiological profile of Brazilian CVD patients through a multicenter, prospective observational study. Conducted across 10 centers nationwide, the study will recruit at least 65 patients per center over 12 weeks. Quality of life will be assessed using the Aberdeen Varicose Vein Questionnaire (AVVQ), with lower scores indicating better quality of life. The Venous Clinical Severity Score (VCSS) will gauge CVD severity, with higher scores indicating greater disease severity. VCSS correlates with the CEAP classification system and ultrasound findings. CVD diagnoses will be categorized using the CEAP classification: C0: No signs of venous disease C1: Telangiectasia/reticular veins C2: Varicose veins (≥3 mm diameter) C3: Edema C4: Skin/subcutaneous changes due to CVD, subdivided into C4a (pigmentation/eczema), C4b (lipodermatosclerosis/Atrophie Blanche), and C4c (corona phlebectatica) C5: Healed venous ulcer C6: Active venous ulcer C6r: Recurrent active venous ulcer During exams, patients will undergo physical evaluation for CVD signs, followed by duplex ultrasound of superficial and perforating veins. These will be conducted in both standing and supine positions by qualified vascular specialists, alongside personal medical history, demographics, occupation, physical stress, and varicose vein symptoms. The study will measure factors including: Presence and location of saphenous vein insufficiency, reflux, and vein caliber Presence of perforating veins and reflux characteristics Presence of deep vein thrombosis and related complications The study also covers therapeutic procedures such as sclerotherapy, endovenous ablation, and surgical vein removal. Compression stockings and pharmacological treatments (e.g., diosmin + hesperidin, calcium dobesilate, troxerutin) will be documented, including usage frequency and duration. Data on cardiovascular diseases, comorbidities (e.g., hypertension, diabetes, dyslipidemia), occupation, and family history of CVD will also be collected, providing comprehensive insights into the risk and impact of CVD on the Brazilian population.

Use of Transcranial Magnetic Stimulation in the Post-Operative Cognitive Dysfunction in Elderly

Postoperative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social, and financial impacts for patients and their communities. Postoperative (PO) cognitive impairments have generally been divided into short- and long-term disturbances. Delirium, a short-term disorder, is defined according to the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) as impairment in attention, awareness, and cognition, fluctuating throughout the day and affected by endogenous and exogenous factors. It has an incidence of 37-46%, differing depending on the type of surgical procedure performed, with reports of up to 51%. In contrast, the term POCD has been used to refer to any new signs of cognitive impairment that exceed the expected time for recovery from the acute effects of surgery and anesthesia, being considered long-term. Among hospitalized PO patients aged 60 years or older, rates of up to 40% have been observed. Considering the aging population linked to a growing demand for surgery, identifying factors that increase the risk of POCD is necessary, as age is the biggest risk factor. Mild Cognitive Impairment (MCI) is one of the main risk factors and is defined as cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition), based on the concern of the individual, caregiver, or clinician. However, these changes do not interfere with the ability to be independent in daily activities. The conversion rate from MCI to dementia is 10 to 15% per year, regardless of any possible influence from anesthesia and surgery. However, there is evidence that anesthesia and surgery may exacerbate the pathological mechanisms of Alzheimer's disease, which could potentially increase this conversion rate. Pre-existing brain, heart, or vascular diseases, low educational levels, and alcohol use are also frequent risk factors. Iatrogenic factors also seem to contribute to POCD. Some articles speculate that POCD in the elderly is attributable to the use of benzodiazepines (BZDs) and anticholinergics (ACs), while others suggest that POCD is independent of the type of surgery or anesthesia used and would result from pre-existing brain fragility. Although a transient fluctuation in cognition during the postoperative period is often not considered concerning, it is important to note that POCD predicts the onset of future dementia and may contribute to chronic neurodegeneration, particularly with repeated surgical procedures.PO cognitive changes can clearly lead to a loss of autonomy in the elderly, prolong hospital stays, generate high medical costs, and increase mortality, making it a serious health and social problem that cannot be ignored. Current theories on the underlying mechanisms of POCD highlight the role of inflammation and immune activation. Surgery itself induces inflammatory processes, localized and systemic expression of pro-inflammatory cytokines, and signaling molecules. Tissue damage after surgery triggers the release of IL-1 and TNF- from endothelial cells and phagocytes, whose elevated levels induce the production of IL-6, increasing the extent of tissue trauma and triggering a cascade of events. The formed inflammatory cascade and cytokine release reach the central nervous system and have a direct relationship with the hippocampus. This brain region contains the highest number of cytokine receptors, has the highest density of IL-1 receptors, and although physiological levels of this cytokine are essential for optimal memory and learning processes in the hippocampus, excessive levels have been associated with decreased cognitive function in animal models. The hippocampus seems especially vulnerable to the harmful effects of systemically elevated inflammatory mediators due to the high density of TNF- receptors and numerous other receptors on the surface of endothelial cells in this brain region. The mechanism underlying impaired learning and memory resulting from excessive levels of IL-1 and other inflammatory mediators in the hippocampus involves harmful effects on long-term potentiation (LTP) and neurogenesis in this brain region, as demonstrated in several animal models. The cognitive reserve is a protective factor for the development of PO cognitive changes and that its increased levels are strongly protective for the incidence of dementia; including higher levels of education, greater occupational complexity, premorbid IQ, and a preference for mentally stimulating leisure activities. Studies in cognitively healthy humans have also shown that physical exercise improved global cognition and was associated with increased gray matter volume, while cognitive exercise was associated with reduced memory loss. Non-invasive brain stimulation (NIBS) techniques are widely used in research and clinical practice, involving the modulation of brain excitability and activity, which can increase or decrease depending on the parameters used, such as transcranial magnetic stimulation (TMS). Numerous in vitro and in vivo experimental models provide evidence that repetitive TMS (rTMS) can enhance long-term potentiation (LTP). LTP is a lasting increase in signal transmission between two neurons resulting from synchronous stimulation. It is one of several phenomena contributing to synaptic plasticity. Memory is thought to be encoded by modifying synaptic strength, so LTP is widely considered one of the main cellular mechanisms underlying learning and memory. These improvements in neural plasticity are observed alongside enhanced performance on hippocampal-dependent cognitive measures. The fundamental basis for brain function is brain oscillations in various frequency ranges. Several studies provide evidence supporting the idea that modulating specific frequency oscillations can alter cognition in healthy individuals. Additionally, rTMS has been used to improve cognitive function through the same mechanism. Particularly, several studies suggest that focal rTMS may promote the alteration and synchronization of human brain oscillations and reveal changes in cognition. According to Hoy and colleagues, neural synchrony refers to the coordinated firing of connected brain regions, which is considered essential for the integration of neural networks and cognitive performance. In other words, rTMS may be an effective oscillatory alteration approach with the potential to improve specific cognitive functions such as attention and perception. New forms of rTMS have recently been developed, including Theta Burst Stimulation (TBS), a new accelerated form of stimulation that more closely mimics the brain's natural firing patterns and may have greater effects on cognitive performance. TBS sessions usually last only 3-10 minutes, compared to conventional rTMS sessions. Faster daily treatments with TBS can allow for increased treatment capacity and reduced costs per session. Improvements in cognitive function using intermittent Theta Burst (iTBS) compared to those using traditional rTMS have been found and may be due to endogenous oscillations. It is important to note that theta and gamma bands have been linked to working memory processes. Oscillations play a critical role in integrating the different brain regions necessary for working memory, with synchronous activity between prefrontal and posterior parietal regions associated with successful working memory encoding. Current findings are promising, revealing a more substantial effect of iTBS compared to the best conventional rTMS protocol investigated so far. These findings indicate that iTBS may be a more suitable and accelerated protocol for cognitive promotion in patients diagnosed with cognitive deficits related to diseases such as Alzheimer's disease and vascular cognitive impairment. However, further patient-based studies with cognitive deficits are needed to explore the effects of iTBS on cognition in real-world settings and different patients. Therefore, the goal of this project is to explore new approaches to postoperative cognitive dysfunction, focusing on its prevention using brain magnetic stimulation techniques. So far, no pre- and postoperative intervention studies have shown robust results in preventing this clinical condition.

A Study of Zasocitinib in Adults With Psoriatic Arthritis Who Have or Have Not Been Treated With Biologic Medicines

A Study of Nipocalimab in Reducing the Risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)