Oporto, Portugal

The PORTuguese Registry of Supera Supported Femoral-Fopliteal Revascularization (SupPORT Registry)

Primary endpoints (at hospitalization, 30 days, 6 months, 1 year) 1. Limb salvage 2. Target lesion revascularization (TLR) 3. Freedom from major adverse limb events (MALE - Major Amputation, any index limb revascularization) Secondary endpoints (at hospitalization, 30 days, 6 months, 1 year) 1. Freedom from Major adverse cardiovascular events (5-point endpoint: Stroke, myocardial infarction/Acute coronary syndrome, Any limb revascularization, Decompensated Congestive Heart Failure, Cardiovascular death1) 2. All-cause death / Cardiovascular death 3. Primary Patency(defined by Duplex Ultrassound Scan [DUS]2) Primary-Assisted Patency, Secondary Patency 4. Ankle-Brachial Index (ABI) 5. Rutherford-Becker classification Inclusion Criteria Clinical - Evidence of symptomatic obstructive peripheral arterial disease - Individuals aged 18 and older - All-comer patients undergoing endovascular lower-limb revascularization with Supera® stent implantation in the superficial femoral (SFA) or popliteal arteries - Patient or legal representative understand the SupPORT registry procedures, and have voluntarily provided informed written consent regarding their participation. - Participant is willing to remain in the SupPORT Registry for at least 1 year. Angiographic - Target lesion is a primary atherosclerotic lesion or a restenosis occurring in a non-stented of the SFA or the popliteal artery, distancing at least ≥ 1 cm from any previously implanted vascular stent. - Target lesion causes a ≥50% arterial obstruction (visually confirmed on digital subtraction angiography). Exclusion criteria - Any contraindication for peri-interventional or post-interventional anti-thrombotic therapy (including, but not restricted to Non-fractioned heparina, low-molecular weight heparina [LMWH], Clopidogrel, Ticagrelol, Ticlopidine, Acetylsalicylic acid, dipiridamol, direct thrombin [factor II] or factor Xa inhibitors, vitamin-K antagonists). - Participation in other research study that may influence obtained results. - Pregnant or breastfeeding women, or expected pregnancy to occur during the study period. - Treatment of intrastent restenosis/occlusion of previous peripheral vascular stent. - Non-corrected hemodynamically significant obstructive arterial disease of the ipsilateral inflow arteries (aorta, iliac arteries) Procedure Protocol - Endovascular revascularization • Participating centers are invited to maintain local practice standards, used in endovascular peripheral arterial revascularization. Pre-implant ballooning and peri-interventional anti-thrombotic therapy will be captured by the database. Intra-procedural and peri-procedural adjuncts are allowed, and will be recorded. Follow-up Protocol - Minimum follow-up will include a clinical assessment up to 30-days post-intervention, at 6 months, and at 1 year. Routine ABI is mandatory. Routine DUS is recommended. - Post-interventional anti-thrombotic therapy will be captured by the database, and will follow international recommendations, but also local practice standards and will be at the discretion of the assisting-physician. Data collection and storage - Data will be inserted at each center by the Investigation team on an electronic platform, created and managed by Infortucano. - Principal Investigators will have access to the enrolled center's participant data. - System components 1. Registry Database All data regarding each participant's records will be anonymously collected in a Central Database, where it will be stored. There are no limits to the number of participating centers. 2. Web Application - SupPORT Registry 1. Registry - The application will run on internet browser, with individual user authentication required for each Principal investigator. This application will allow the recording of the data and follow-up data by each participating center. 2. Information extraction - Inserted data by each center/investigator will be only accessible to each center/investigator during the study period. The Registry administrator will have access privileges to all participants' data. The application will provide general tables/graphics with generic information throughout the study period, accessible to all investigators (number or participants per center, overall inclusion, to be defined). All inserted data will be exportable to CSV files, allowing import to Microsoft Excel or SPSS software. 3. Technological architecture - All components are developed Microsoft.NET platform. The web application will be developed on ASP.NET 3.5/4.0. The Database Management System (DBMS) will be Microsoft SQL Server 2012/2019. The used Web Server will be Microsoft IIS 7.0. 4. Storage - The Central System and DBMS will be lodged in Safe Cloud Microsoft Azure Servers (InforTucano). The application address will be www.rnsupport.com. Cloud Microsoft Azure Server Characteristics: - Physical Location: Western Europe (The Netherlands) - Data backups with differential archives of the previous 15 days - Availability - 99,9 % - Anti-virus ESET File Security for Windows Server - Double-Firewall (Windows Server e Microsoft Azure Firewall) - Test version: http://test.infortucano.pt/RegistoSupPORT - User: admin - Pwd: admin123 Statistical analysis Statistical analysis: Continuous variables with a normal distribution will be described as mean and standard deviation. Continuous variables are presented as median and interquartile range (IQR) if skewed and will be tested among groups using the Mann-Whitney U-Test for independent samples. Related variables will be compared with the Wilcoxon Signed Rank Test. Categorical variables will be presented as count and percentage and will be compared using the Pearson's χ2 test or the Fisher´s exact test in cases of low number of events. Life-table based analyses will be used for endpoint assessment. Kaplan-Meier curves will be created, and differences tested according to the log rank test. For association between baseline characteristics endpoints, a multivariable logistic regression model (including time as a co-variate) or a Cox hazards proportion model will be created including variables with α-value ≤0.10 on univariate analysis, if appropriate. Stepwise backward elimination of variables with a P-value >.050 will be also used during multivariable modelling. Confidence-intervals of 95% (95%CI) will be used and statistical significance will be considered for α<.05. All statistical analyses will be performed using Statistical Package for Social Sciences 21.0 (IBM Inc, Chicago, Ill, USA).

RehabGBs: Rehabilitation in People With Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy and is the most common cause of acute flaccid paralysis. Its annual global incidence is between 0.8 - 1.9 cases per 100,000 people. GBS is usually preceded by infection or other immune stimulation that induces an aberrant autoimmune response targeting peripheral nerves and their spinal roots. It is characterized by rapid progressive bilateral muscle weakness of the lower limbs and/or arms, in combination with hyporeflexia or areflexia, and most patients reach their maximum disability within 2-4 weeks.Various phenotypes have been described, including acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor sensory axonal neuropathy and Miller-Fisher syndrome. Overall, the clinical course, severity and outcomes of people with GBS are highly heterogeneous. Significant disability, including incomplete recovery of motor (i.e., ambulation) and sensory function, as well as fatigue, pain, respiratory insufficiency and psychological distress might exist after the acute phase. But long-term significant impacts, two years after the onset, on daily activities, work, social activities and health-related quality of life have also been reported. The most often feature is an impairment of the motor capacity, but respiratory muscle weakness is a common complication in people with GBS and may result in decrease vital capacity, chest wall expansion and coughing strength, causing atelectasis and pulmonary infections. Therefore, it is generally accepted that respiratory muscle weakness causes increased morbidity and mortality, owing to the combination of poor airway protection, inadequate secretion clearance and hypoventilation. Previous studies already identified these clinical manifestations in acute GBS. However, prevalence of hypoventilation and inspiratory muscle weakness in subacute phase of GBS is still unknown. Early recognition and treatment of respiratory muscle weakness is important in people with GBS and physiotherapy interventions may be useful to successfully manage these patients. Inspiratory muscle training (IMT) is a cheap and free of side-effects therapeutic modality, which consists of breathing exercises using a pressure threshold device, that has been applied in several diseases. In patients with chronic obstructive pulmonary disease, IMT improve inspiratory muscle function, exertional dyspnoea and exercise capacity. In patients with neuromuscular disease, has been suggested that IMT increases inspiratory muscle strength and lung volumes, especially in those with muscular dystrophies. In addition, a randomized control trial concluded that IMT in acute patients increases inspiratory muscle strength and quality of life. However, there are no studies about rehabilitation approaches, such IMT, to improve symptoms (i.e. dyspnoea or fatigue), pulmonary function, functional status and quality of life in people with GBS. Rehabilitation, namely inpatient rehabilitation programmes, is therefore key for the recovery of symptoms, functional outcomes, community participation and quality of life of these highly complex patients. Nevertheless, insufficient high-quality literature, still precludes definitive conclusions about the effects of rehabilitation in people with GBS. Additionally, the interpretation of the magnitude of its effects is challenging due to the lack of minimal clinically important differences (MCIDs) for most outcome measures used in rehabilitation of people with GBS. A MCIDs is the smallest change in a measure that will be perceived as an important improvement for the patient. Such values constitute thresholds for clinical meaningfulness. Therefore, establishing MCIDs is essential to determine effectiveness of rehabilitation and guide clinical decision-making in the management of people with GBS. In conclusion, by developing and implementing RehabGBs, we will contribute to build evidence-based rehabilitation practices and optimise care in GBS, by: i) assessing the effects of IMT in people with GBS; ii) establishing minimal clinical important differences of rehabilitation outcome measures, to help clinicians better understand the magnitude of the effects of the intervention and determine effectiveness of rehabilitation in people with GBS; iii) evaluate the prevalence of nocturnal hypoventilation in people with GBS. Therefore, the primary aim of RehabGBs is to: 1. Evaluate, through a randomised controlled trial, the effects of InspireGBs - inspiratory muscle training protocol on respiratory muscle strength, peak cough flow, lung function, dyspnoea, fatigue, functional status and quality of life in people with GBS. The secondary aims of the project are to: 1. Establish the MCIDs for rehabilitation programmes in people with GBS for Functional Assessment of Chronic Illness Therapy-Fatigue Subscale, Modified Borg Scale, Medical Research Council - Manual Muscle Testing, Vital capacity, Maximal Inspiratory pressure, Peak Cough Flow, Functional Independence Measure and EuroQol Five-Dimensional Questionnaire. 2. Evaluate the prevalence of nocturnal hypoventilation in people with sub-acute GBS. Study Design & Intervention InspireGBs is an inspiratory muscle training programme which will be implemented to people with GBS for 6 weeks during an inpatient rehabilitation programme. They will receive IMT for 5 days/week using the PowerBreath KH2. This handheld device applies a constant resistance provided by a electronic-controlled valve. Training will be set initially at a load of approximately 50% of patients' maximal inspiratory mouth pressure. This initial load will be daily increased during the programme based on symptom scores (modified Borg dyspnoea Scale ratings of 4-6 of 10).Total daily training time will consist of 6 cycles of 30 breaths (3 cycles, twice daily). Patients will be recruited as described and randomly allocated by a computer-generated adaptive random allocation schedule (in a ratio 1:1) to either the experimental or control groups. All participants will receive the inpatient rehabilitation programme. This programme will be tailored to each patient, with approximately 5 hours of intervention/day for 5 days/week (typically for 14 weeks). An interdisciplinary team composed of physiotherapy; occupational therapy; speech and language therapy; and medical, pharmacological, nursery, psychology, clinical dietitian and social worker will be involved, as needed. Sample Size Estimation Based on an inspiratory muscle training study conducted in people with spinal cord injury, it is anticipated that a minimum of 64 participants (32 in each group) will be needed to detect a between-group difference of 10 cmH2O in the primary outcome measure (power=80%, α=0.05, 2-tailed). Since in GBS rehabilitation interventions dropout rates are around 15%, 74 participants will be needed.

Study of Efficacy and Safety of LNP023 in Participants With Active Lupus Nephritis Class III-IV, +/- V

The overall purpose of this two-part study is to evaluate the efficacy, safety and tolerability of iptacopan (LNP023) in addition to standard of care treatment.

A Study of TAK-330 to Reverse the Effects of Factor Xa Inhibitors For Adults Needing Urgent Surgery

International CIPN Assessment and Validation Study

The study will be performed at all participating centers and will consist of the following assessments: Core study (assessments at baseline and at the end of treatment) - Standard oncology assessment per local site - NCI-CTC (national cancer institute common toxicity criteria) v.5 sensory and motor - PRO-CTCAE (patient reported outcome-cancer common tocixity adverse event) - PI-NRS (pain intensity numeric rating scale) - NPS-CIN (Neuropathic Pain Scale for chemotherapy-induced neuropathy) - EORTC CIPN20© (The European Organisation of Research and Treatment of. Cancer Quality of Life Questionnaire-CIPN twenty-item scale) - FACT-GOG NTX v.4© (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity) - TNSn© (total neuropathy score, nurse version) - PGIC (patient global impression of change) - OXA-NQ (oxaliplatin neurotoxicity questionnaire) Extended study (at all available sites - any combination of assessment methods is allowed, minimum at baseline and at the end of treatment) - EORTC CIPN15 - CIPN-R-ODS (CIPN Rash overall disability scale) - TNSc© at the same time points as for questionnaire - OXA-NQ (also at mid-treatment) - nerve conduction study of the radial (motor and sensory), ulnar (motor and sensory), sural, dorsal sural and common peroneal nerves (*) - QST (*) [quantitative sensory testing] - Serum for biomarkers search (*) - DN4 Rationale: Within a multi-center international collaboration among experienced neurologists, oncologists, nurses and symptom scientists, the principal aim of this study is to evaluate responsiveness of a set of outcome measures for CIPN evaluation in order to define the gold standard for its assessment. The assessment of CIPN will be performed at different levels of investigation. The Core study will allow the evaluation of subjects with common devices, so that an assessment can be performed at any medical site (expected time for questionnaires completion 15 minutes). The Extended study will add any combination of the listed assessment methods/biological sample collection, in order to ascertain whether this approach can provide a more careful and clinically-relevant estimate of the peripheral nervous system damage. Comparison between healthcare evaluation and subjects' report of CIPN severity using established questionnaires will be performed in both Core and Extended studies. Aims: The primary aim for this study is to test responsiveness of the different assessment methods used in the core study, in a multi-center, multi-regional International setting, comparing changes from baseline to end of treatment. Secondary aims are: - to evaluate responsiveness (changes from base line to end of treatment) also of the other outcome measures used in the Extended Study; - to evaluate mid-treatment data predictiveness of end of treatment neurological status for each outcome measure; - to evaluate recovery rate/modification of the neurological status for the follow up evaluations (3/6/12/24 months after treatment), stratifying data for different drugs. Study Design: 1000 patients who are candidates for neurotoxic chemotherapy for any cancer with non-investigational drugs (including immune checkpoint inhibitors and "targeted" drugs) will be enrolled from participating centers. A trained investigator in each participating center will perform the selected healthcare-assessed scales and supervise the patient-completed measures as presented in Table 1. Subjects will be examined at least at baseline and end of treatment (Core Study) and at additional intermediate and follow-up timepoints (Extended study), according to their treatment plan. Study Treatments: There are no study-specified treatments, as subjects will receive only their standard of care chemotherapy. The investigators will not influence decisions regarding treatment duration nor supply medication for this study. However, all treatment regimens will be registered. Participating Centers minimum requirements: Participating Centers should: 1. accept the study protocol and have their participation approved by a local Ethics Committee/Institutional Review Board 2. have access through an internet connection to the secure server located at the main site 3. guarantee the proper assessment of the selected patients at least at the Core study level 4. have the potential to recruit at least 30 patients/year 5. have the capacity to upload the data collected from each patient within 1 week

Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL

A Safety and Efficacy Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-Severe Symptom State

Acquired from Horizon in 2024.

A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma

A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma

Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Previously Untreated Follicular Lymphoma