Brain Injury

The purpose of this study is to determine if an investigational drug can prevent Bronchopulmonary Dysplasia, reducing the burden of chronic lung disease in extremely premature infants, as compared to extremely premature infants receiving standard neonatal care alone.

The GENESIS study is a multicenter, prospective, non-interventional, clinical study with a target of 12,000 subjects and an anticipated total duration of 36 months. The aim of study GENESIS is to provide a pilot map of HLA genetic variation in the Greek population in order to be used in medical research and for possible clinical applications (evaluation of possible correlations with selected underlying diseases). During the study, each subject will conduct one visit to the participating cite, in which they will provide: 1. Demographic information \[i.e. date of birth, gender, race, ancestry (including information about the subject's grandparents' birthplace), height, weight\], 2. Other information about smoking/vaping, alcohol consumption, arterial blood pressure, diagnosed diseases (if any), current treatments (if any), and 3. Recent (up to 12 months prior to sample collection) results if/when are available from clinical lab tests such as blood count (Hct, Hb, RBC, WBC, PLT count), including a metabolic panel, liver enzymes and biochemical parameters (Glu, HbA1c, TC, TG, LDL-C, HDL-C, ALT, AST, ALP, γGT, bilirubin, LDH, insulin, C-peptide). Upon completion of the data registry, two buccal swabs will be collected per subject and they will be stored at ALTP premises until their shipment to Galatea.Bio. All buccal swab samples will be subjected to genetic material (DNA) extraction. The DNA samples will be further proceeded for HLA genotyping analysis. A follow up analysis will be performed in selected DNA samples via full low-pass whole genome sequencing (LP-WGS), which aims to further investigate the association between the HLA region and autoimmune diseases. Upon completion of the analysis, an individualized ancestry report will be securely made available to all study subjects which they can access, as and if they elect to.

Intensive Care Units (ICUs) are stressful places fraught with grief for family members who witness dying loved ones, often in pain, struggling to breathe and/or maintain consciousness. Compounding their distress, family members are often thrust into the position of patient "surrogate," needing to make life-and-death decisions on the patient's behalf. Researchers have shown that end-of-life (EoL) decision-making is undermined by grief, which interferes with acceptance of the patient's impending death and leads to care choices that adversely affect patients' quality of care and death.1-3 These circumstances heighten surrogates' risk of meeting criteria for Prolonged Grief Disorder (PGD), Posttraumatic Stress Disorder (PTSD), and decisional regret about the EoL care that the patient received, each associated with poor bereavement outcomes.4-7 Nearly 60% of ICU surrogates report moderate to extreme grief; 34% report extreme levels of peritraumatic stress symptoms.1 The coronavirus (COVID-19) pandemic has made an already bad situation worse. At the start of the pandemic, social distancing policies forced millions of families to confront obstacles to communication, medical decision-making, and care.8-10 Surrogates were left struggling with severe pre-loss grief and peritraumatic stress -- intensely longing to be near to the patient, confused about their roles, lonely, horrified, angry, disoriented and emotionally numb.10,11 Now, as the Delta variant creates a new "wave" of mortality and infection, bereaved family members may have remorse about vaccine refusal,12 feel guilty for transmitting the virus to the patient, or regret decisions about EoL care. With over 35 million cases and 600,000 deaths in the United States from COVID-19,13 the need for psychosocial interventions to support surrogates in the ICU is clear. Prior efforts to address the plight of family surrogates of critically ill patients have proved disappointing14-20 - with one ICU intervention significantly increasing the surrogate's severity of PTSD symptoms.14 A key limitation of these interventions is that while they targeted psychological outcomes, they were not psychological interventions. To address this, the investigators developed a brief, flexibly administered cognitive-behavioral, acceptance-based psychological intervention called EMPOWER (Enhancing \& Mobilizing the POtential for Wellness \& Emotional Resilience).21,22 Our pilot NIH-R21 (N=39) showed that EMPOWER had superior efficacy to enhanced usual care for reducing symptoms of PGD (d=1.20) and PTSD (d=.99). Consistent with mediation, EMPOWER reduced experiential avoidance (d=1.20); these reductions were correlated with PGD and PTSD change scores (p\<0.01). Large reductions in decisional regret (d=1.57) were observed, with no notable differences by surrogate race or delivery format (telehealth vs. in-person). Investigators propose to conduct a Phase II mixed methods randomized controlled trial (RCT) to further evaluate the efficacy of EMPOWER for reducing surrogate symptoms of PTSD and PGD. Surrogates (N=172) will be randomized to EMPOWER (n=86) or a standardized supportive conversation (SC; n=86). Effects of the intervention will be assessed via measures administered pre-intervention (T1), immediately post-intervention (T2), and at 3 months (T3), and 12 months (T4) following the T2 assessment. Investigators will also conduct semi-structured interviews with surrogates (n≈48) to probe intervention effects on mental health and explore contextual factors (e.g., medical mistrust, visitation restrictions) likely to affect surrogates during the pandemic.

Aims/Hypotheses: Primary Aim: To determine the recommended maximal safe dose of LEV in the setting of neonatal seizures of mild to moderate severity. If 60mg/kg LEV does not control seizures, subjects will be randomised to receive either additional LEV or PHB. LEV dose will be escalated in 30mg/kg increments to a maximal dose of 150mg/kg total loading dose. We will use a continual reassessment method to determine the maximal safe and tolerated dose. Secondary/exploratory aims: * To study the pharmacokinetics of high dose LEV in neonates with seizures of mild to moderate severity. * To estimate the additional efficacy of higher doses of LEV in neonates with seizures of mild to moderate severity. * To improve technologies for the prompt detection of neonatal seizures: We will assess the latest version of Persyst's neonatal seizure detector. Research Design This is a Phase IIb, open label dose-escalation, preliminary safety and efficacy study. An active drug treatment control arm (PHB group) is included in the study design. This study is not designed or powered to compare high dose LEV and PHB groups, however, the randomized control group will help with interpretation of adverse events and seizure cessation efficacy seen in the high dose escalation group. This is particularly important because of the high rates of morbidity in neonates with seizures. 24-hour seizure control endpoint: cEEG reviewed by a neurophysiologist will be used for assessing 24-hour seizure control. Treatment will be considered effective in achieving 24-hour seizure control if there is a seizure burden less than 30 seconds in the 24 hours following the dose. Change in seizure burden in 2-hour post treatment period will also be assessed. Intervention If seizure activity occurs participants will be enrolled and will receive 60mg/kg LEV. If seizures continue babies will then be randomised to receive either: * Additional LEV at a higher dose (30 mg/kg, 60 mg/kg, or 90 mg/kg depending on the stage of the study), OR * PHB at 20-40 mg/kg. Maintenance treatment will continue for 5 days, either IV or orally if baby is tolerating feeds. LEV discontinuation or addition of PHB: there are multiple criteria for transition to, or addition of, PHB treatment if required for seizure control.

The primary objective of this clinical study is to characterize in Chinese toddlers ages 32 - 42 months old the developmental characteristics of MRI measured neural flexibility, as an index of cognitive flexibility, and to assess a range of executive functions (inhibit, shift, emotional control, working memory, plan/organize) using the Global Executive Composite summary score obtained from the BRIEF-P standardized rating scale.

Gliomas are invasive and aggressive tumors, which derive from glial or stem cells, and after neoplastic transformation, acquire glial cell characteristics. Treatment of high-grade gliomas includes measures to relieve symptoms and eliminate or control the tumor. Surgery, radiation, and chemotherapy are the most common options. Recent findings revealed that dietary interventions to reduce glucose and glycolytic pathways could have a therapeutic effect. CKD is a restrictive therapeutic diet consisting of a 4:1 ratio of fat-to-CHO and protein. Fat provides up to 90% of the caloric intake, while overall CHO intake is less than 50 g/day. CKD reducing blood glucose levels and increasing ketone body levels stimulates biochemical changes to achieve systemic ketosis. Though, evidence for CKD in clinical practice is still limited. This study focuses on the classic ketogenic diet (CKD), adjusted for each patient's energy needs by dieticians to achieve ketosis. The primary outcome is to assess the efficacy of CKD to extend the survival of patients with high-grade gliomas and brain metastases. Historical controls will be used to compare the outcome measurements.

2\. INTERVENTION The first phase of the intervention will last four weeks and will be done in the hospital. After this intervention, if the patients meet the inclusion criteria, they will be enrolled in the second phase, which will be done at the patient's home for two additional weeks. Three assessments will be performed during the study: The first one ("Day 0") will be assessed before starting the treatment, the second one will be done ("Week 4") directly after the intervention at a hospital setting, and the last one ("Week 6"), after the home intervention. The intervention will be conducted in 1-hour sessions three times a week for four weeks, performing different exercises using an augmented reality platform accessed through RGSweb. If the patients continue the intervention at home, a three-session training for two weeks will be conducted in the presence of a patient's relative, who will accept to be the training partner. 3\. EQUIPMENT AND TECHNICAL SPECIFICATIONS. RGSweb can be used with any computer or device with a camera. However, our target users are patients who might have visibility issues due to old age. Therefore, bigger screens will be used to enhance the patients'; visibility. Additional screen support will be required to hold the monitor. There are three protocols in RGSweb: Twister Buddy: It has been developed for balance training, which involves a series of levels intended to strengthen the muscles crucial for maintaining upright posture, notably those in the legs. The aim is to improve stability and help prevent falls. Levels The user will have to shift their weight from one leg to the other while doing different exercises, such as touching targets with their hands and feet or taking steps. All levels will start with a calibration phase to ensure the user is in the correct position. Level 1 -Balance: In this level, two colored columns will be displayed on the screen, while user motion trackers will also be reflected on the screen. The goal is to align the trackers with the same color column. Level 2 - Balance + Hands: In addition to the balance movement from Level 1, a target will be displayed on the screen. The user must maintain balance on the highlighted column while reaching the target with their hand. Level 3 - Side Steps: To initiate, the user must have their feet on a square-like target at the bottom center of the screen. After that, a target will appear adjacent to the square. The user's task is to adjust their foot position so that both the toe and heel are inside this target area. Once achieved, the user must return their foot to the original position within the square, prompting the appearance of the next target for the opposite foot. Level 4 - Front steps: Similar to level 4, the user begins by positioning both feet on the square target. Then, an arrow will appear above one of the user's feet, indicating the direction of the step (either forward or backward). Once the user moves the designated foot past a predefined threshold value, currently indicated by a slider, the arrow will disappear, prompting the user to return both feet to the square. Subsequently, an arrow will appear above the other foot, indicating the direction for the next step. The direction of the steps is randomized for each interaction. Level 5 -- Balance + Hands + Feet: This is the next step from level 4. It starts with Balance, then the target for the hand, and finally, the target for the opposite foot. Like level 2, the user must maintain only the bottom part (hip and under) inside the column while reaching the target with their hand and foot. Costume Party: This protocol's main focus is sit-to-stand. The levels of this exercise follow different steps to stand up from a chair, starting with leaning forward. Levels All levels will start with a calibration phase to ensure the user is in the correct position. The objective is to dress up for a costume party using a reference shown at the bottom right of the screen. Various costume parts will appear on a bar and move across the screen. The user needs to catch the right parts for their costume and put them on. Once the costume is complete, there will be a few seconds to admire it before the process starts over with a new costume reference. Level 1-Lean Forward: In this level, the costume elements move from one side of the screen to another at the user's eye level. To grab the element, they must lean forward enough to surpass a threshold value defined by a slider. Level 2-Flex Knees: The user starts the motion of standing up by flexing the knees and rising slightly from the chair. The elements will appear close to the user's head, and leaning forward is unnecessary. Level 3-Stand Up: This level is similar to level 2, but the elements are positioned higher, requiring the user to stand up to reach them. Gentle Giant: This exercise targets less-impaired patients who can perform sit-to-stand and balance training exercises. Levels: The aim is to allow the elements to move from one platform to another following color coding. To do so, the user will act as a bridge between the different floors. All levels will start with a calibration phase to ensure the user is in the correct position. Level 1-Squats: In this level, the user must move the elements from one platform to another by moving the bridge up and down, that is, by squatting to go down and standing again to come up. Level 2-Tip-Toe: In this level, one platform will be higher than the user's height. The aim is similar, though: The user must stand in a tip-toe position to move the bridge higher and connect the platforms.

Veterans face a "deadly gap" during their first year of transition from military to civilian life with limited available psychiatric services and increased suicide risk factors. During this critical transition period, Veteran suicide rate is double that of active service members and the general Veteran population. An average of 20 Veterans die from suicide each day, but only 6 of the 20 use VA services. VA care engagement has been shown to mitigate suicide risk; therefore, promoting engagement during the "deadly gap" could be essential to suicide prevention. Transitioning Veterans require outreach and services to provide them with support in their access to VA healthcare, suicide prevention education, and skills to manage their transition effectively. This proposal would bridge this important healthcare gap using STEP-Home. STEP-Home is an evidence-based, transdiagnostic, video telehealth rehabilitation workshop to improve reintegration, social support, and functioning among Veterans with high clinical comorbidity. STEP-Home is non-clinical, cost-effective, and skills-focused to maximally engage Veterans not participating in treatment who may be resistant to traditional "mental health" diagnostically focused approaches. To date, STEP-Home has not been adapted for the unique needs of recently transitioning Veterans or augmented for suicide prevention. This proposal will adapt and refine STEP-Home specifically for recently transitioning Veterans and add suicide prevention content and skills to create STEP-Home-SP. The proposed pilot study is designed to support STEP-Home and suicide prevention content experts in their refinement and evaluation of STEP-Home-SP. The investigators will utilize the VA/Department of Defense Identity Repository (VADIR) to recruit recently transitioned Veterans nationwide. In Aim 1, the investigators will develop STEP-Home-SP by adapting the STEP-Home telehealth intervention to specifically target recently transitioned Veterans and augment the workshop to include suicide prevention. In Aim 2, the investigators will conduct a two-arm proof-of-concept acceptability and feasibility randomized controlled trial (RCT) of STEP-Home-SP versus Enhanced Usual Care (EUC=current standard of care + educational packet on suicide risk and connection to VA care) in recently transitioned Veterans. Lastly, the investigators will explore reintegration status, VA care initiation, and candidate outcomes for STEP-Home-SP relative to EUC to inform a future full-scale RCT. If successful, fostering social, vocational, and community connection; building emotion regulation and impulse control skills; facilitating safety planning; and providing education and access to VA care upstream should result in decreased suicide risk during this critical transition and beyond.

The use of deep brain stimulation (DBS) has expanded to include multiple conditions in children including dystonia, epilepsy, Tourette syndrome and mood disorders. Despite its growing application, DBS remains a low-volume procedure in most pediatric centers, which limits opportunities for large-scale research studies. To overcome this challenge, an international data-sharing platform is essential for advancing knowledge about DBS in pediatric patients, particularly concerning surgical techniques and patient outcomes across various conditions. This study aims to establish a multicenter pediatric DBS registry. With limited data on pediatric DBS outcomes and a small number of cases at individual centers, there is a need for a comprehensive registry to enable large-scale, well-powered analyses of DBS safety and effectiveness. The primary goals of this study are to: * Establish and implement a multi-center pediatric DBS registry * Facilitate large-scale analyses of DBS safety and effectiveness in children * Refine DBS as a treatment option for dystonia and other hyperkinetic movement disorders in children. Secondary objectives include: * Identifying which patients benefit most from DBS * Determining clinical variables that influence DBS responsiveness * Identifying optimal implant sites for specific conditions * Understanding the long-term effects of DBS in children * Assessing the impact of DBS on the quality of life in pediatric patients The study will involve both prospective and retrospective data collection from pediatric DBS patients.

This is a retrospective, multicenter cohort study using anonymized electronic health record data collected in a prospective study (PORC -EDGE 2364) performed at UZA and an identical prospective data collection performed by collegues at Department of Sleep Laboratory and Sleep surgery at Heim Pal National Pediatric Institute at Budapest.Data are collected from otherwise healthy children and children with varying comorbidities undergoing (adeno)-tonsillecty for Obstructive Sleepapnea (OSAS). Per-postoperative management was carried out according to a predefined treatment protocol. As this study uses existing data, no informed consent was required. The aim of the current project is to answer the following questions. * What is the prevalence of Postoperative Respiratory Complications (PORC) in children undergoing surgical treatment for OSA and is the prevalence different according to the underlying comorbid condition (i.e obesity, craniofacial malformation, syndromes Down syndrome, neurological conditions affecting upper airway muscle tone)? * Which factors are associated with the occurrence of PORC (Polysomnogram (PSG) related factors such as obstructive Apnea-Hypopnea Index (oAHI), minimum oxygen saturation during PSG, and patient related factors such as age at time of surgery, presence of a comorbidity)? * Is it possible to develop a management algorithm for postoperative management based upon the risk factors for PORC above.