Suzuka-shi, Japan

Effects of tDCS-enhanced Cognitive Control Training on Depression

Develop a Multi-disciplinary Approach for a Personalized Prenatal Diagnostics and Care for Twin Pregnancies

This is a multi-center study to identify biomarkers or marker combinations for early prediction of pregnancy complications in twin pregnancies in the first, second or third trimester. In the future, the identified patients' risk will enable patients' referrals for proper prevention when such will become available Specifically the investigators aim for - Predicting the risk to develop preeclampsia, IUGR, preterm delivery, gestational Diabetes Melitus - Assessment of major and minor markers for chromosomal and structural anomalies - Identification of placenta accrete spectrum disorders and vasa previa - Diagnosis of specific MC twin complications such as TTTS The investigators will stratify and assess all the above according to chorionicity and delivery with complications at <32 weeks, <34 weeks, <37 weeks, and at any gestation. Screening methods will be conducted in the first, second or third trimester or at any gestation Also the investigators aim to Identify the risk to lose one or both twins at <32 weeks, <34 weeks, <37 weeks and at any gestation, the ability to predict fetal birth weight at <32 weeks, <34 weeks, <37 weeks and at any gestation The investigators also aim for monitoring any of the following maternal complications including placental abruption (clinically or on placental examination), postpartum hemorrhage (defined as blood loss ≥1 L within the first 24 hours after birth) at <32 weeks, <34 weeks, <37 weeks and at any gestation. The investigators will monitor 1. Neonatal morbidity due to intraventricular hemorrhage (IVH) grade II or above - Defined as bleeding into the ventricles, Grade II (moderate) - IVH occupies <50% of the lateral ventricle volume, Grade III (severe) - IVH occupies ≥50% of the lateral ventricle volume or Grade IV (severe) - Hemorrhagic infarction in periventricular white matter ipsilateral to a large IVH 2. Neonatal sepsis confirmed bacteremia in cultures, anemia defined as low Hemoglobin and / or hematocrit requiring blood transfusion, respiratory distress syndrome defined as need for treatment by surfactant and ventilation, necrotizing enterocolitis requiring surgical intervention, and composite of any of the above 3. Newborn admission to neonatal intensive care units (NICU), length of stay and therapies during the admission. 4. Ventilation defined as a need for a positive pressure (continuous positive airway pressure (CPAP), nasal continuous positive airway pressure (NCPAP)) or intubation and a composite of any of the above 5. Any maternal complications within the first 6-10 weeks post delivery. The investigators will recruit patients in the different sites aiming for 1200 twin pregnancy and will collect the patients' entire pregnancy data for developing an algorithm to calculate the risk to develop the complications 6. Evaluation of serologic response to BNT162b2 Pfeizer/BioNTech vaccination.

PASS of Paediatric Patients Initiating Selumetinib

Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant genetic disorder that is caused by germline mutations in the NF1 tumour suppressor gene, which encodes the tumour suppressor protein neurofibromin 1. Plexiform neurofibromas (PN) are histologically benign nerve sheath tumours, which typically grow along large nerves and plexi. On 5 March 2020, a centralized Marketing Authorisation Application was submitted to the European Medicines Agency (EMA), Marketing Authorization in EU was granted on 17 Jun 2021. As part of the approval process, a Risk Management Plan (RMP) was developed and submitted to the EMA to summarise the safety concerns emerging from the clinical development program. The RMP included additional pharmacovigilance plans for a non-interventional Post-authorisation Safety Study (PASS) to further characterise the safety of selumetinib in paediatric patients with NF1-related PN in routine clinical practice. The RMP version 1.0 (succession 4) approved by EMA on 22 April 2021 had 1 important identified risk with selumetinib treatment: -LVEF reduction The RMP also identified 5 important potential risks with selumetinib treatment: - Physeal dysplasia - Ocular toxicity - Myopathy - Hepatotoxicity - Choking on the capsule Long-term exposure (including long-term safety data on developmental toxicity in children) was identified in the RMP as an area of missing information. The planned non-interventional PASS will address gaps in knowledge identified by the RMP, including the important identified risk and some of the potential risks and missing information on long-term developmental toxicity in children, by characterising the safety profile associated with selumetinib use among paediatric patients (aged d 8 to < 18 years old) with a diagnosis of NF1 with symptomatic, inoperable PN. This study is a specific obligation in the context of a conditional marketing authorisation for selumetinib (ie, Category 2 PASS). Study results will contribute to updating the safety profile of selumetinib in a relatively large population of patients with different personal characteristics across multiple health care systems and patterns of real-world clinical practice in up to 52 specialist clinics for the treatment of pediatric patients with NF1 across up to 12 European countries and in Israel. The primary objective of this study is: - To characterise the safety of selumetinib, including up to 6 years of long-term safety, in paediatric patients with NF1-related symptomatic, inoperable PN, 8 to < 18 years old who have not reached Tanner Stage V at the start of selumetinib treatment (Nested Prospective Cohort). The secondary objective of this study is: - To describe the demographic and clinical profile of the paediatric population 3 to < 18 years old with NF1-related symptomatic inoperable PN who start selumetinib in routine clinical practice (Base Cohort). The study observation period was anticipated to begin in Q2 of 2022, with some variation by country (actual start date was 23 May 2022). Patients will be enrolled after selumetinib access is commercially available and patients are able to receive the medicine as part of local clinical practice. The target population for this study are patients with NF1 in the EU with symptomatic, inoperable PN who have been prescribed at least 1 dose of selumetinib and who are aged 3 to < 18 years at the start of selumetinib treatment, except for those patients receiving treatment with a mitogen-activated protein kinase inhibitor before the index date. The study will enrol 2 cohorts: 1. The Base Cohort includes all enrolled patients aged 3 to < 18 years. 2. The Nested Prospective Cohort will include the subset of Base Cohort patients aged 8 to < 18 years who have not reached Tanner Stage V on the index date. Patient screening will be conducted throughout the enrolment period and baseline data for all patients will be abstracted from medical records. Those meeting the criteria for enrolment in the Nested Prospective Cohort will be followed up during their routine standard of care visits with the treating clinician (expected to occur every 6 to 12 months) for up to 6 years.

Next Generation Sequencing Diagnostics - On the Road to Rapid Diagnostics for Rare Diseases

In the study NextGen SE (single-center, prospective, open diagnostic study) are on-hand a cohort comprising each 50 pediatric and 50 adult patients, and in which there are an unclear movement disorder or an unclear cognitive disorder, examines the following questions: Primary: - Number of diagnoses made by next-generation sequencing (NGS) Secondary: 1. Restriction of the quality of life by unclear disease 2. Cost of not purposeful preliminary diagnostics (beyond the minimal diagnostic data of the diagnosis to therapy and follow-up examinations 3. Time to diagnosis

Preference-based Comparative Study on Definitive Radiotherapy of Prostate Cancer With Protons

The hypothesis of the study is a 7.5% decrease of combined genito-urinary and intestinal side effects from 15% with photon therapy to 7.5% by the use of protons. With an alpha of 0.05 and 80% power it is therefore necessary to treat 131 patients with protons to detect such difference. With an estimated drop-out rate of 10% 146 patients have to be recruited to the proton arm. As randomization to photon or proton therapy is not possible in a multicenter setting with only few proton facilities available patients treated with photons will be prospectively matched to their proton counterparts. Stratification criteria will include: Age, high dose volume, androgen deprivation, history of surgery, obstructive disease, increased risk for rectal bleeding, socio-economic criteria and use of rectal balloon during radiotherapy. Comparison of the primary endpoint will be restricted to patients without irradiation of lymphatic drainage.

Product Surveillance Registry

The NEU-STIM Trial

Rationale: A randomised study demonstrated that preterm infants who received repetitive stimulation at birth (10 second episodes of stroking of the soles of the feet and/or back, followed by 10 seconds rest) showed an increase in respiratory effort. This may in turn improve clinical outcomes as improved breathing effort may reduce the need for invasive respiratory support. Tactile stimulation can be immediately and easily performed at birth at no extra cost. It therefore has great potential to be implemented in delivery rooms (DRs) worldwide. Objective: To determine the effect of repetitive tactile stimulation compared to selective stimulation on oxygenation of the infant at 5 minutes after birth. Study design: This is a stepped-wedge cluster randomised controlled trial. The participating centre, rather than the individual infant, will be the unit of randomisation. This design is appropriate to test the effect of an intervention that encompasses a behavioral aspect - in this case the performance of tactile stimulation. Study population: Infants born before 32 weeks of gestation will be included in this trial. Intervention: At the start of the study, each participating centre will perform selective tactile stimulation in accordance with international guidelines, as is their usual practice. Clinicians will gently rub the back, chest, extremities or soles of the feet if they consider the breathing of the infant to be insufficient or absent. In the second stage of the study, centres will be randomised to switch their stimulation approach to repetitive stimulation. Clinicians will then gently rub the back, chest, extremities or soles of the feet for 10 seconds. To avoid extinction of the stimulatory effect (reflex), every 10 second period of stimulation will be followed by 10 seconds of rest (no stimulation). Repetitive stimulation will be performed for the first 5 minutes of life, or longer if the breathing is still considered insufficient or absent. Main study parameter: The proportion of infants with pre-ductal oxygen saturation (SpO2) ≥ 80%.

BPL-003 Efficacy and Safety in Treatment Resistant Depression

Approximately 225 eligible participants will be receive a single dose of either low, medium, or high doses BPL-003, given intranasally, with 8 weeks of follow-up assessments. Psychological support will be given before, during and after dosing.

A Study of Roxadustat to Treat Anemia in Children and Teenagers With Chronic Kidney Disease