Upper Respiratory Infection

This is a randomized, blinded, controlled phase I clinical trial with a total of 120 participants aged ≥ 60 years. Experimental group: Influenza virus split vaccine (0.7mL/vial), control group 1: Influenza virus split vaccine, control group 2: placebo group. The three groups were recruited at a ratio of 1:1:1, and 40 individuals were randomly vaccinated in each group. Each person was injected with one dose of the vaccine into the deltoid muscle of the upper arm. Participants in each study group are required to undergo laboratory indicator tests before and on the 4th day after vaccination.

The main aim for POS-ARI-PC is to provide a platform for continuous data capture for patients with ARI presenting to primary care settings across Europe, covering cases caused by known and emerging respiratory pathogens with epidemic and pandemic potential, in order to generate observational evidence to inform care and maintain study- readiness for RCT evaluations. The POS-ARI-PC platform will thereby support the efficient set-up of new clinical studies and trials, which will be embedded into the platform. We have developed two overarching protocols for the POS-ARI-PC. The POS-ARI-PC AUDIT protocol allows for a flexible annual anonymous prospective audit-type registration to describe the presentation and management of patients presenting in primary care with ARI. This provides the infrastructure for patient sampling and follow-up, and in which randomisation can be activated for platform trials to evaluate a range of interventions that can be added and replaced over time. This has resulted in the POS-ARI-PC CORE protocol. POS-ARI-PC AUDIT: This is a flexible annual anonymous prospective audit-type registration to describe the presentation and management of patients presenting in primary care with ARI. POS-ARI-PC AUDIT will be delivered through a prospective, multi-country, audit-type anonymous registration of presentation and management of approximately 2,000 patients presenting to PC annually across Europe. This audit will benchmark the case mix and care of patients consulting in PC. These can include general practice, urgent care centres, accident and emergency and other acute services in hospitals, for adult and paediatric patients, both in and out of office hours. POS-ARI-PC CORE: This is a non-randomised, prospective, observational study of the presentation, management, microbiology and outcome of acute respiratory tract infection in primary care. POS-ARI-PC CORE has the following three objectives: Objective 1. A prospective, observational study of ARI patients in primary care to undergo study-specific sampling upon inclusion and be followed up for 28 days to capture the aetiology of their ARI and describe clinical outcomes. Objective 2. A qualitative study with research professionals, clinicians, and patients to a) gain a deep understanding of the research process, and the meaning of results and to identify barriers and opportunities for implementation of changes considering findings, and b) explore the views and experiences of patients who consult European primary care services for ARI symptoms since the COVID-19 pandemic. Objectives 3. To ensure research readiness for including embedded observational and randomised evaluations to answer questions about the effectiveness of diagnostic, behavioural or therapeutic management strategies for ARI in PC. When a new embedded observational study or RCT is added to the POS-ARI-PC a study-specific appendix (SSA) or an intervention-specific appendix (ISA) will be developed which details the (changes in) the study population, the research question, objectives, outcomes, study-specific processes and analysis. This will be appended to the POS-ARI-PC CORE Protocol and all appropriate approvals will be gained for each SSA or ISA. Participation in the study will last for 28 days. Once consented to the study, a member of the study team will complete a short questionnaire collecting the participants' names and contact information, some details about them, and the symptoms they have been experiencing. A combined throat/nose swab will be collected from the patient for study purposes. Participants will also be asked to tell us about how they are feeling today and for the next 14 days via an online or paper daily diary. They might be telephoned to ask some questions if they are unable to complete the daily diary. Their GP will be contacted after day 28 to collect information about their consultations and hospital referrals in the 28-day period. A small number of enrolled participants who consented (optional) to be contacted by the research team about the nested qualitative study will be invited for a process evaluation interview. POS-ARI-PC-001: The first embedded study, POS-ARI-PC-001, will be conducted as a prospective observational study to estimate the incidence of medically-attended RSV, HMPV, HPIV and RV infections in an elderly population. This embedded study is appended to the POS-ARI-PC CORE Protocol as a study specific appendix (SSA).

The aim of the present study is to establish a modified minimally invasive surgical technique for sinus floor augmentation with a residual bone height of 3-6mm. Hypothesis: The investigators expect that the present surgical technique allows to achieve an adequate implant bed of at least 10mm height after a healing period of 3-5 months. Further the modification of the technique enables a reduced patient stress level.

The DiaSorin Molecular LIAISON® NES FLU A/B, RSV \& COVID-19 real-time polymerase chain reaction (RT-PCR) assay is intended for use on the DiaSorin LIAISON® NES instrument for the in-vitro qualitative detection and differentiation of nucleic acid from influenza A, influenza B, RSV and SARS-CoV-2 virus from dry nasal swabs (NS) from human patients with signs and symptoms during the acute phase of respiratory tract infection in conjunction with clinical and epidemiological risk factors. The LIAISON® NES FLU A/B, RSV \& COVID-19 assay is intended for use as an aid in the differential diagnosis of influenza A, influenza B, RSV and SARS-CoV-2 infection in a professional laboratory setting. Negative results do not preclude influenza A, influenza B, RSV or SARS-CoV-2, infection and should not be used as the sole basis for patient management decisions. The assay is not intended to detect the presence of the influenza C virus.

Research questions and hypotheses i) Is a non-pharmacological cough control therapy feasible to treat chronic cough in patients with ILD? Hypothesis: Given the results of previous non-pharmacological interventions in patients with refractory cough, we predict that this intervention will be feasible and well accepted in patients with ILD. ii) Is a non-pharmacological cough control therapy more effective than pulmonary rehabilitation (PR) alone to treat chronic cough in patients with ILD? Hypotheses: Given the results of previous non-pharmacological interventions in patients with refractory cough, we predict that improvements observed in participants receiving the non-pharmacological intervention will exceed those receiving PR alone. Improvements are expected in HRQOL (exceeding the minimal clinically important difference), intensity of cough-related sensations and symptoms of fatigue. Research Design The proposed research is a feasibility pre-post intervention study. Study details: Adults with ILD and chronic cough will be enrolled in this study. Potential eligible patients will be recruited from the outpatient PR program at West Park Healthcare Centre and St. Joseph's Healthcare. As the outpatient pulmonary rehabilitation program at West Park Healthcare Center and St. Joseph's Healthcare will transition partially to virtual meetings, the interactions between the research team and patients will be completed via phone calls or online. This research study will be delivered online using the Zoom Healthcare Plan, an online platform that is available at West Park Healthcare Centre, and is used for telerehabilitation programs. Participants will be enrolled into a PR program composed of aerobic and strengthening exercises, disease-specific education and self-management, as part of their usual care. Two weeks before termination of PR, participants will start the non-pharmacological cough control therapy, following the intervention proposed by Chamberlain colleagues (2017). Participants will attend four virtual sessions of 45 to 60 minutes of educational and self-management This study will measure several clinical outcomes. 1. Feasibility will be reflected by the number of eligible patients enrolling (enrolment rate of at least 75%) and completing the intervention (attendance rate of at least 80%), compliance with the sessions and adverse events. 2. Leicester cough questionnaire 3. The King's Brief Interstitial Lung Disease (KBILD) 4. Modified Borg scale (mBorg 5. Cough Hypersensitivity Questionnaire (CHQ) 6. Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) 7. Global rating of change questionnaire (GRCQ) 8. Satisfaction Semi-structured interviews using open-ended questions will be conducted before and after the cough control intervention to capture participants' expectations and perspectives about the cough control therapy.

This Phase 1 study is designed to assess the safety, tolerability, and pharmacokinetics of single and multiple intravenous doses of BWC0977 when administered to healthy adult volunteers. This is a randomized double-blind, placebo-controlled, ascending dose, multi-cohort trial. A total of 64 healthy volunteers are expected to be enrolled in 8 Cohorts. The study will be conducted in two phases: A single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants in Cohorts 1 - 2 will receive one dose of BWC0977 or placebo. In MAD, participants in cohorts 3 - 7 will receive multiple doses of BWC0977 or placebo for 7-10 consecutive days (as per the schedule). In both parts, sequential cohorts will be exposed to increasing doses of BWC0977.

Several influenza antivirals are licensed, differing in availability and routes of administration. Direct comparisons of antiviral and clinical efficacy between the multiple available antivirals are lacking. This comparative information is important for guideline development and for aiding purchasing and prioritisation decisions with several options available. The platform trial will assess the following interventions: * Licensed influenza antiviral interventions: oseltamivir (TAMIFLU®), peramivir (RAPIVAB®), zanamivir (RELENZA®), laninamivir (INAVIR®), baloxavir (XOFLUZA®) and favipiravir alone and in combination. The interventions will be chosen in order of priority as well as local feasibility at sites (availability of drugs, local ethics committee and regulatory approvals) * Interventions with antiviral activity against influenza demonstrated in pre-clinical studies: molnupiravir Randomisation to the no antiviral treatment control arm (no intervention) will be fixed at a minimum of 20% throughout the study. The randomisation ratios will be uniform for all available interventions.

This is a Phase IIa, open-label, multiple ascending dose confirmation, multicenter study to evaluate the safety and tolerability of intravenous Brincidofovir (BCV, SyB V-1901) 0.2 mg/kg, 0.3 mg/kg, or 0.4 mg/kg dosed BIW or 0.4 mg/kg dosed QW (Cohorts 1 to 4) in adult and pediatric subjects with AdV viremia, and IV BCV in subjects with CMV.

This Phase 3 multi-center, randomized, open-label study will assess efficacy of IV BCV, compared to IV CDV, in allo-HCT subjects with AdV viremia. Randomized subjects will be treated for up to a maximum of 12 weeks of therapy for both arms. Primary efficacy assessment will be performed at W5D1. Consistent with ECIL guidelines for high-risk patients, AdV viremia will be assessed weekly. Subjects randomized to receive BCV or CDV are treated until AdV DNA is confirmed to be undetectable in plasma for two consecutive tests 7 days apart, or until Week 12 post W1D1, whichever occurs first. Subjects will continue BCV or CDV as long as AdV viremia is detectable, contingent on tolerability, until viremia clears, or the subject reaches a maximum duration of 12 weeks of study drug treatment. Subjects will receive assigned randomized therapy until time of AdV virological success plus 2 weeks, for up to a maximum of 12 weeks. All subjects will be followed through 24 weeks. All study visits and follow-up assessments must be completed regardless of the study drug treatment duration. All subjects are considered on study through the Week 24 follow-up visit. For subjects who achieve virological success from their initial randomized study drug treatment and experience an AdV viremia recurrence, repeat treatment with their randomized study drug is allowed. There is no cross-over study drug treatment allowed in this study and subjects can only receive retreatment with their randomized study drug. Subjects who stop study drug therapy due to confirmed undetectable AdV viremia may re-initiate study drug treatment if AdV viremia is subsequently confirmed at ≥ 1000 IU/mL by the designated central virology laboratory (recurrence). For the purposes of re-initiating study drug therapy, "confirmed viremia ≥ 1000 IU/mL" is defined as two consecutive results ≥ 1000 IU/mL from the designated central laboratory, with the second sample drawn at least 48 hours after the first sample. Subjects who permanently discontinue study drug therapy for toxicity reasons are not eligible to re-initiate study drug dosing. Study procedures are to be followed during these Retreatment visits as applicable for BCV and CDV outlined in the schedule of assessments (SOA). An independent Data Safety Monitoring Board (DSMB) will review accumulated safety data for this study when total combined enrollment in both arms is approximately 25% (45 subjects) and 50% (90 subjects). They will also review adverse events on an ongoing basis. They will make recommendations to the Sponsor based on review of these safety data. Further details regarding data safety monitoring guidelines will be included in the DSMB Charter. The DSMB will make determinations regarding continued enrolment and/or stopping the study for safety reasons. An Endpoint Adjudication Committee (EAC) will be convened to evaluate baseline diagnosis and AdV disease clinical response as outlined in the EAC charter.

It is a multicenter, adaptive open-label, non-randomized, dose-escalation, and expansion study to assess safety, tolerability, and efficacy following intracochlear administration of SENS-501.