Sisli-istanbul, Turkey

Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults.

Long-term Safety and Efficacy of Odevixibat in Patients With Alagille Syndrome

This Phase 3, open-label, multi-center extension study will have two groups of participants: Cohort 1 (participants who participated in Study A4250-012 [NCT04674761; ASSERT] and meet the entry criteria for this study) and Cohort 2 (infants under 12 months of age) with ALGS. The study will consist of 2 or 3 periods: 1. A 'Treatment period' of 72 weeks (cohort 1) or 12 weeks (cohort 2). Participants will visit the clinic every 4 to 12 weeks and will receive a dose of 120 μg/kg odevixibat daily. 2. An 'Optional extension period' where participants who wish to continue receiving odevixibat after the 'treatment period' will have the opportunity to remain on treatment with visits every 16 weeks until the drug is commercially available. The optional extension is available provided continued use is supported by the risk-benefit profile, the participant has not been previously withdrawn or discontinued from the study, and the study is not terminated by the Sponsor. 3. A 'Safety follow-up period' of 4 weeks (cohort 1) or 2 weeks (cohort 2). The Safety Follow-up Period will not occur for those who remain on treatment in the optional extension period. Participants will need to complete an e-diary and questionnaires throughout the study (cohort 1 only). Participants will undergo blood samplings, urine collections (cohort 1 only), physical examinations, and clinical evaluations. They may continue some other medications, but the details need to be recorded.

Patisiran-Lipid Nanoparticle (LNP) Pregnancy Surveillance Program

Optimizing INITIation of Non-invasive Ventilation in ALS Patients

First visit: After informed consent the following data which are gathered as parts of usual care will be recorded in the case report form (CRF): - Pulmonary function: - FVC ( % predicted) upright and supine - capillary blood gas analysis, room air (pH, pCO2, HCO3-, pO2) - anamnestic questions (Borg scale 0-4) - Gender - Age - Percutaneous Endoscopic Gastrostomy (PEG)/ Percutaneous Radiological Gastrostomy (PRG) tube: yes/no - Medication - Weight/ BMI - Living situation - Civil status - The following clinical characteristics from their medical record (from neurologist or rehabilitation specialist): - Date of diagnosis - Type of ALS at onset - ALSFRS-R at the time of diagnosis - Pulmonary function at the time of diagnosis - Cognitive status (ECAS, ALS-FTD-Q) - Medical history - Validated questionnaires (online): - Quality of life questionnaires (SF 36, ALSAQ-40) - Respiratory insufficiency questionnaire (SRI) - ALS FRS R (patient version) - Bulbar symptoms questionnaire (CNS BFS) After the first visit patients will participate in one of the two cohorts (non-randomized): - Cohort 1: patients who start NIV in the first two months after the first visit to the HMV - Cohort 2: patients who do not start NIV in the first two months after the first visit to the HMV. Cohort 1: Data will be recorded at the moment of initiation of NIV and 3, 6 and 9 months after initiation. Data will be recorded during regular visits (to the HMV centre or at the patients home). - Pulmonary function: - capillary blood gas, room air (pH, pCO2 (kPa/ mmHg), HCO3- (mmol/l), SaO2 (%)) - anamnestic questions (Borg scale 0-4) - Nocturnal gas exchange by transcutaneous measurement, at the patients home - Mean tcpCO2 (kPa), Maximal tcpCO2 (kPa), mean oxygen saturation (%), lowest oxygen saturation (%) - Data from NIV equipment (compliance, modus, IPPA, EPAP, freq, mask type) - Use of NIV - hours a day/night - In case of no use: why not? - PEG/ PRG tube: yes/no - Survival - Tracheostomy or not - Weight - Validated online questionnaires: - Quality of life questionnaires (SF 36, ALSAQ-40) - Respiratory insufficiency questionnaire (SRI) - ALS FRS R (patient version) - Bulbar symptoms questionnaire (CNS BFS) - Nocturnal gas exchange, transcutaneous, at the patients home Cohort 2: Data will be recorded every 3 months until initiation of NIV or death or max 1,5 years after the first visit to the HMV. Data will be recorded during regular visits (to the HMV centre or at the patients home). - Pulmonary function: - Capillary blood gas (pH, pCO2 (kPa/ mmHg), HCO3- (mmol/l), SaO2 (%)) - anamnestic questions (Borg scale 0-4) - Nocturnal gas exchange by transcutaneous measurement, at the patients home - tcpCO2 (kPa), Maximal tcpCO2 (kPa), oxygen saturation (%), lowest oxygen saturation (%) - PEG/ PRG tube: yes/no - Survival - Tracheostomy or not - Weight - Cognitive status (from medical record) - Reason for not starting NIV - Validated online questionnaires: - Quality of life questionnaires (SF 36, ALSAQ-40) - Respiratory insufficiency questionnaire (SRI) - ALS FRS R (patient version) - Bulbar symptoms questionnaire (CNS BFS) - Nocturnal gas exchange, transcutaneous, at the patients home If a patient in cohort 2 will start with NIV, the patient will be transferred to cohort 1.

A Research Study to Look at Long-term Treatment With a Medicine Called NNC6019-0001 for People Who Have Heart Failure Due to Transthyretin Amyloidosis

Intradermal Ipilimumab and Nivolumab in High Risk Stage II Melanoma

Lifestyle InterVEntion Study in General Practice: LIVES - GP

Rationale: Patients with depression are at a substantially increased risk of chronic physical disease including cardiovascular disease. This may be attributed primarily to an unhealthy lifestyle related to their disorder. Interestingly, the unhealthy lifestyle feeds back to decreased quality of life and increased depressive symptoms, thus creating a hazardous vicious circle. Consequently, there is a great potential for 'Lifestyle Medicine' for depression. Yet, it is known that patients with depression often have motivational and self-management problems. Therefore a multimodal lifestyle intervention (MLI) specifically tailored to the needs of depressed patients was developed and piloted in mental health care, with promising results. This research aims to investigate this MLI in general practice because this is the setting where the majority of patients with depression are treated and results from mental health care are unlikely to apply. Objective: to estimate in general practice the feasibility of conducting a large-scale study on the effectiveness of a MLI for depression, and identify key factors that can influence its successful conduct. In addition, this study aims to obtain an estimate of the variance of outcome measures (mental health, lifestyle factors, functioning, recovery, wellbeing, sleeping quality, self-esteem, quality of life, health care costs, anthropometry and blood pressure). Study design: An observational single-group prospective cohort study (n = 50) using mixed methods with baseline measurement and two follow-up measurements: after the intervention at 18 weeks and after a follow-up at 42 weeks. Study population: Patients (18 years or over) with depression and overweight who are being treated in general practice. Intervention (if applicable): A MLI named (in Dutch) "Gecombineerde Leefstijl Interventie Leef" (GLI-LEEF), developed for patients with depression consisting of several modules (e.g. on physical activity, healthy diet) comprising both individual and group sessions. Main study parameters/endpoints: implementation feasibility using three of the elements of the 'Reach, Effectiveness, Adoption, Implementation, Maintenance' (RE-AIM) framework for process evaluation (i.e. Reach, Adoption and Implementation)

Potassium Correction for RAAS Optimization in Chronic Kidney Disease

The PROMISE trial is a randomized, double-blind, placebo controlled cross-over trial where individuals are participating for 36 weeks. The trial consists of a 6-week run-in period, followed by two 12-week study periods, separated by a 6-week washout period. First, during a run-in period, each participant will be converted from their ACEi/ARB dose to irbesartan 150 mg once daily. Individuals who already used irbesartan 150mg once daily before trial participation will remain on this dose during the run-in period. After six weeks, blood and 24-hour urine samples will be collected (baseline visit) and participants will be randomized to patiromer or placebo (start of study period A). The participant, research team, and treating physician will be blinded to treatment allocation (patiromer or placebo), while irbesartan will remain open-label. At one week after start of study period A and B, participants will perform a home blood pressure measurement and visit a local lab to verify the plasma potassium level (safety visit), in combination with a scheduled phone consultation. The following actions may be taken: 1) If plasma potassium is >5.0 mmol/L or eGFR is >25% lower than baseline, the dose of irbesartan will be reduced to 150 mg/d and remain so during the remainder of the study period; 2) If systolic blood pressure is <110 mmHg, the participant has symptoms of hypotension, and plasma potassium is <5.0 mmol/L, antihypertensive co-medication may be adjusted, if applicable. If there is no antihypertensive co-medication that can be adjusted, the irbesartan dose will be reduced to 150 mg/d during the remainder of the study period. At six weeks after start of the study period, there will be an in-hospital study visit. Blood samples will be collected, and office blood pressure will be measured. Any of the same two actions as described above may be taken in case of hyperkalaemia, severe acute kidney function decline or hypotension, respectively. At the end of each 12-week study period, blood and 24-hour urine samples will be collected, and home (as well as office) blood pressure will be measured to establish the study endpoints. In addition, the study medication (patiromer/placebo) will be stopped and irbesartan dose will be reduced (or maintained) at 150 mg once daily. After a 6-week washout period, the second baseline will take place (measurements identical to the first baseline), which marks the start of study period B. During study period B, participants who had been randomized to patiromer in period A will now receive placebo and vice versa. The measurements during study period B will be identical to period A. At 12 weeks after the start of study period B, the protocol is completed and patients will return to their original medication. The investigators chose a cross-over study design to be able to use participants as their own control; this will enhance statistical power and reduce the number of required participants. Based on previous studies, it is known that 6 weeks are sufficient to reach stable albuminuria and blood pressure after an ARB dose change. Therefore, even if halfway the 12-week study period a dose reduction is made, there is enough time for albuminuria and blood pressure to stabilize before the end of the study period (i.e., when the primary endpoint is established). A 6-week washout period is inserted to avoid carry-over effects.

Improving Diagnosis and Prediction of Outcome in Patients With Severe Disorders of Consciousness

In order to identify patients with a good neurological outcome a combination of diagnostic tests is used. Clinical rating scales - Simplified evaluation of consciousness scale (SECONDs) and the full outline of unresponsiveness (FOUR) score - Once a week Blood biomarkers - Neuron specific enolase, neurofilament light, glial fibrillary acidic protein - Sampling timepoints: 24h, 72h, 7 days and 14 days after brain injury - Serum (STG-5) and plasma (EDTA-6) tubes, aliquoted (4 x 0.5ml) and stored at -80°C EEG with reactivity testing - Standard 21-electrode montage - Stimuli protocol I: a set of 5 stimuli repeated 3 times 1. Auditory: clapping in hands, 2. Auditory: calling patients name loudly, 3. Visual: passive eye opening, 4. Tactile: nasal tickle, 5. Noxious: sternal rub Each stimuli is applied for a duration of 5 seconds and an interval between stimuli of 30 seconds - Stimuli protocol II: Cognitive-motor dissociation test MRI-scan - Sequences considered essential for patient care i.e.T1, T2, FLAIR, DWI/SWI - Preferably, performed between 4-6 weeks after hospital admission