S.-petersburg, Russian Federation

Efficacy and Safety of Stempeucel® in Patients With Critical Limb Ischemia (CLI) Due to Peripheral Arterial Disease

Title: An Observational, Practice-Based, Open Label, Feasibility Study to Observe the Efficacy and Safety of Intramuscular Administration of Stempeucel® in Malaysian Patients with Critical Limb Ischemia (CLI) Due to Peripheral Arterial Disease Study Design: Single arm, practice-based, feasibility study Study Duration: Estimated duration for the main protocol (e.g. from starts of screening to last subject processed and end of the study) is approximately 18 months Study Center: Universiti Kebangsaan Malaysia Medical Centre (UKMMMC), Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Wilayah Persekutuan, Malaysia Objectives: To observe the efficacy and safety of Stempeucel® (adult human bone marrow derived, cultured, pooled, allogeneic mesenchymal stromal cells) in Malaysian patients with critical limb ischemia (CLI) due to peripheral arterial disease. Investigational Medicinal Product Description • Ex-vivo cultured allogeneic mesenchymal stem cells (MSCs) supplied in cryo-bags consisting of 150 or 200 million, suspended in 50 ml of Plasmalyte A containing 1.5% human serum albumin (HSA) and 3% dimethyl sulfoxide (DMSO). Dosage • Dosing of Stempeucel® is based on body weight. The recommended dose is 2 million cells/kg body weight. Administration • 40 - 60 injections administered as 0.6 ml/kg (200 million bag) or 0.8 ml/kg (150 million bag) intramuscularly into different points on the muscle. Additional injections of 2 ml (200 million bag) or 3 ml (150 million bag) administered around the ulcer Number of Subjects: 10 patients Data Analysis Data Management: - Electronic case record form (eCRF) will be used for data entry. - Oracle clinical (or other suitable alternatives with audit trail) will be used for data management. Statistical Method: - The SPSS® package (IBM Inc., USA, version 22) will be used for statistical evaluation. - All patients in the study with relevant efficacy and safety data will be considered for the analysis. - Efficacy analysis will be done using GEE (Generalized Estimating Equations) method or paired t test as appropriate. - Adverse events monitored using information voluntarily disclosed by the patients and as observed by the PI will be summarized descriptively by total number of AE(s). - AEs will be categorized as: all AEs, all treatment-emergent AEs, all severe AEs, treatment-related AEs and severe treatment-related AEs. These events will be reported as appropriate and summarized.

Efficacy and Safety of Stempeucel® in Patients With Critical Limb Ischemia (CLI) Due to Buerger's Disease

Title: An Observational, Practice-Based, Open Label, Feasibility Study to Observe the Efficacy and Safety of Intramuscular Administration of Stempeucel® in Malaysian Patients with Critical Limb Ischemia (CLI) Due to Buerger's Disease Study Design: Single arm, practice-based, feasibility study Study Duration: Estimated duration for the main protocol (e.g. from starts of screening to last subject processed and end of the study) is approximately 18 months Study Center: Universiti Kebangsaan Malaysia Medical Centre (UKMMMC), Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Wilayah Persekutuan, Malaysia Objectives: To observe the efficacy and safety of Stempeucel® (adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells) in Malaysian patients with critical limb ischemia (CLI) due to Buerger's disease. Investigational Medicinal Product Description • Ex-vivo cultured allogeneic mesenchymal stem cells (MSCs) supplied in cryo-bags consisting of 150 or 200 million, suspended in 50 ml of Plasmalyte A containing 1.5% human serum albumin (HSA) and 3% dimethyl sulfoxide (DMSO). Dosage • Dosing of Stempeucel® is based on body weight. The recommended dose is 2 million cells/kg body weight. Administration • 40 - 60 injections administered as 0.6 ml/kg (200 million bag) or 0.8 ml/kg (150 million bag) intramuscularly into different points on the muscle. Additional injections of 2 ml (200 million bag) or 3 ml (150 million bag) administered around the ulcer Number of Subjects 3 patients Data Analysis Data Management: - Electronic case record form (eCRF) will be used for data entry. - Oracle clinical (or other suitable alternatives with audit trail) will be used for data management. Statistical Method: - The SPSS® package (IBM Inc., USA, version 22) will be used for statistical evaluation. - All patients in the study with relevant efficacy and safety data will be considered for the analysis. - Efficacy analysis will be done using GEE (Generalized Estimating Equations) method or paired t test as appropriate. - Adverse events monitored using information voluntarily disclosed by the patients and as observed by the PI will be summarized descriptively by total number of AE(s). - AEs will be categorized as: all AEs, all treatment-emergent AEs, all severe AEs, treatment-related AEs and severe treatment-related AEs. These events will be reported as appropriate and summarized.

Factors Associated With Infant Circadian Rhythm, Growth, and Temperament

Circadian rhythm is the body's internal clock that synchronizes the body's physiological functions according to the 24-hour sleep-wake cycle. An individual establishes a circadian rhythm 3 months after birth, which is a progressive phase that involves regulating hormones such as cortisol and melatonin. According to previous studies, the synchronization of circadian rhythm between mother-infant pairs have been found to be beneficial in the growth and development of the child by regulating a 24-hour sleep-wake cycle. However, circadian disruption may cause excessive maternal cortisol which can be transferred to the fetus through the placenta during pregnancy and cause growth retardation. Growth faltering during infancy is associated with increased risks of morbidity from infections and chronic diseases in later life. Therefore, it is important to study the relationship between maternal circadian rhythm with synchronization of infant circadian rhythm as it may be one of the potential factors which affects the growth and development of the child. On the other hand, infant temperament is affected by the maternal and infant circadian rhythm and may also be a predictor to mood disorders such as depression and anxiety. A systematic review reported that high cortisol levels during third trimester of pregnancy is associated with higher emotional reactivity and more difficult temperament infants. Other than the biological factors determining infant temperament, maternal psychological wellbeing during and after pregnancy is also an important element. It has been found that elevated maternal stress was associated with negative infant temperament, resulting in decreased sleep quality of the infant. Negative infant temperament may be a predictor to disordered eating behaviors and growth development. As infant temperament is an important factor in determining growth and development, the risk factors to negative temperament should be studied. This study aims to determine the role of prenatal and postnatal factors with the infant circadian rhythm and its relationship with infant growth and temperament at 6 months. This study also includes the validation of the Chrononutrition Profile Questionnaire (CPQ) among pregnant women. Through the validation of CPQ, future research about chrononutrition behaviors and eating misalignment can be conducted to replace food record. The design of this study is a prospective observational cohort study. Data will be collected during 3rd trimester of pregnancy, whereas follow-up data on birth outcomes will be collected at birth. At 3 months after birth, data on maternal and infant circadian rhythm will be assessed, then data on growth and development will be collected at 6 months after birth. Data collection is elicited through a properly designed and validated questionnaire namely Chrononutrition Profile Questionnaire (CPQ), Harvard Light Exposure Assessment (H-LEA), sun exposure habits, Morningness-Eveningness Questionnaire (MEQ), Positive and Negative Affect Schedule (PANAS), Pittsburgh Sleep Quality Index (PSQI), and Edinburgh Postnatal Depression Scale (EDPS). Meanwhile, anthropometric data such as gestational weight gain and birth outcomes are gathered from clinic record. In addition, data on infant sleep, feeding, behavior, and light exposure will be collected using Brief Infant Sleep Questionnaire (BISQ), infant feeding log, Baby Eating Behavior Questionnaire (BEBQ), Infant Behavior Questionnaire- Revised (IBQ-R), and infant light exposure log sheet. Cortisol levels will be determined using salivary cortisol method where maternal and infant saliva samples are collected at 3 time points: upon awakening, noon (10:00 to 12:00), and evening (19:30 to 21:00). Understanding the potential factors affecting infant circadian rhythm offers new insights in understanding modern lifestyle factors and its association with fetal programming, infant growth, and development.

ARCHERY - Artificial Intelligence Based Radiotherapy Treatment Planning for Cervical, Head and Neck and Prostate Cancer

Full Pulpotomy Versus Root Canal Treatment for Teeth With Symptomatic Irreversible Pulpitis

Diuretic Efficacy of Aminophylline and Furosemide Combination vs Furosemide Alone in Critically Ill Adults

EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics

This is an open-label, multinational, randomised, superiority trial. Patients will be randomised to control and intervention arms. Patients randomised to the intervention arm, will have the BioFire Blood Culture Identification 2 Panel (BCID2) used for positive blood cultures and/or the BioFire FilmArray Pneumonia or Pneumonia plus Panel for respiratory tract specimens if having hospital-acquired pneumonia or ventilator-associated pneumonia. Standard of care diagnostics will also be used. Antibiotic guidelines will be provided to clinicians to aid interpretation of test results and treatment prescription. Ceftazidime-avibactam will be available for targeted use in patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales. Patients randomised to the control arm, will have samples analysed by clinical microbiology laboratories using standard of care diagnostics. Antibiotics will be available to these patients as per usual institutional practice. The main population that will be recruited in the study will be hospitalised patients with bloodstream infections, hospital-acquired pneumonia or ventilator-associated pneumonia due to Pseudomonas aeruginosa or carbapenemase producing Enterobacterales treated with ceftazidime-avibactam, while the secondary population recruited will be those with multidrug resistant (MDR) Gram-negative bacilli. The enrolment criteria are based on the US Centers for Disease Control and Prevention criteria for healthcare-associated infection surveillance. Clinical and mortality outcomes will be assessed for 60 days post infection. The infection causing bacterial isolates will be collected for genotypic description via whole genome sequencing. The total target sample size is 1900 participants in the main population over 20 study sites.

Improvement of Laryngoscopic View by Bed-up-head-elevated Position During Tracheal Intubation in Paediatric Patients

This is a prospective observational study comparing POGO score during tracheal intubation in SP and BUHE position in paediatric patients aged 3 to 12 years who will undergo elective surgery under general anaesthesia requiring tracheal intubation. The first POGO score will be obtained during SP followed by second POGO score during BUHE position and the difference in POGO score before and after BUHE position will be recorded to learn the improvement in POGO score during BUHE position. The objective of this study is to learn the improvement of laryngeal view in tracheal intubation after BUHE position in paediatric patients of age 3 to 12 years. Investigators hypothesised that laryngeal view in tracheal intubation improves after BUHE position compared to sniffing position.

Analgesic Effect of IntraPeritoneal LIGNOcaine in Gynaecological Open Surgery

Postoperative pain impedes the progress of recovery and increases the risk of postoperative complications, namely lung atelectasis, incidence of desaturation, pulmonary dysfunction and chronic pain. Although opioid is the one of the gold standard analgesia for postoperative pain, it comes with many unwanted adverse effects, such as respiratory depression, hypotension and incidence of nausea and vomiting. Thus, multimodal analgesia regime, including local anaesthetic is strongly advocated for postoperative analgesia. Lignocaine is a local anaesthetic agent, which has the properties of analgesia, anti-inflammatory and anti-arrhythmia effect via the blockade of sodium channel receptor in the spinal cord and dorsal root ganglia. The intravenous lignocaine exerts its effect via the systemic absorption of drugs to block the central neuronal transmission. In recent years, studies have demonstrated that intraperitoneal route of lignocaine can reduce visceral pain by inhibiting peritoneal free nerve ending and reduce peripheral neuronal hyper-excitatory of pain signal transmission. It is also believed that intraperitoneal lignocaine is associated with minimal systemic absorption of drug and lower incidence of systemic toxicity local anaesthesia as compared to the intravenous route of lignocaine. Several randomised controlled trials (RCTs) showed the beneficial effect of intraperitoneal lignocaine for the reduction of postoperative visceral pain after laparoscopic surgery. However, gynaecological open surgery has greater degree of organ manipulation and tissue injury with greater visceral pain, resulting in longer duration of hospitalisation and delayed functional mobility recovery. It is believed that the intraperitoneal lignocaine reduces inflammatory response after surgery and exert analgesia effect by blocking the neural pain signal transmission at site of tissue injury. The dosage of intraperitoneal lignocaine used in the literature ranged from 200-400mg. The serum concentration of intraperitoneal lignocaine was measured, which was associated with a relatively safe serum concentration of lignocaine. Pharmacological studies have showed that the adjuvant dose of adrenaline reduced the systematic absorption of intraperitoneal lignocaine. Therefore, this study is designed to examine the analgesic effect of intraperitoneal lignocaine in gynaecological open surgery. The investigators hypothesised that intraperitoneal lignocaine reduces postoperative pain score at rest and movement in women undergoing gynaecological open surgery.

A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard endocrine therapy in patients with ER+/HER2 - early breast cancer who completed definitive locoregional therapy (with or without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and up to 5 years. The planned duration of treatment in either arm of the study is 60 months. The eligible patients must have intermediate or high risk of recurrence, as defined by specified clinical and biologic criteria. Prior use of CDK4/6 inhibitors is permitted. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.