Datasets:

pat-jj

/

ClinicalTrialSummary_Simple

like 0

Probiotics and passive immunoprophylaxis are classes of dietary supplements that are lawfully marketed in the US for maintenance of gut health (GH). This randomized, double-blind, clinical trial will evaluate one commercially available dietary supplement products (passive immunoprophylaxis (Travelan®), compared with placebo, to assess their ability to maintain normal gut function during travel. The results of this clinical trial will be used to evaluate the use of Travelan® to maintain GH during deployment and travel and is not intended to support a marketing application of any dietary supplement as a drug or biological product for human use. This study is a multi-site, randomized, placebo-controlled, double-blind clinical trial conducted on travelers and deployed US and United Kingdom (UK) military personnel. The study will test Travelan®, compared with placebo for maintenance of GH during and immediately after travel. Enrollment of 868 deployed military personnel or travelers will occur at sites within the Uniformed Services University of the Health Sciences (USU) Infectious Disease Clinical Research Program (IDCRP) network and the UK military. Subjects will be randomized to receive a masked regimen of Travelan® or placebo taken as 1 sachet twice daily with meals. Chemoprophylaxis will be started 2 days prior to arrival and maintained for a maximum duration of 20 days (minimum of 10 days) during travel or deployment. Stool smears collected during travel will be used for evaluating the microbiome and for gut pathogen identification. Paired (pre and post-supplement administration) sera and stool samples (pre- and post-supplement administration) will be collected for testing of exploratory objectives. Primary Endpoint (Efficacy): The primary efficacy endpoint is the combined endpoint of incidence of GH disruption (defined as 3 or more unformed stools in a 24-hour period) OR 2 or more unformed stools and one or more associated symptoms (nausea, vomiting, abdominal pain, fever, bloody stool) in a 24-hour period OR antibiotic treatment for diarrhea per subject report, during the period of prophylaxis. Primary endpoint data will be obtained from review of the Travel Diary. Secondary Objectives: Secondary endpoints will include an evaluation of compliance with each dietary supplement and tolerability (e.g. taste, bloating, flatulence, etc.); these will be assessed using the Travel Diary. Differences in GH associated enteropathogen distribution among the 2 treatment groups will be determined by testing stool smears collected by subjects during a GH deficit using a polymerase chain reaction (PCR) assay. Exploratory objectives related to changes in the gut microbiome with dietary supplement use and proteomic signatures of the host-pathogen interaction will be addressed contingent on the availability of additional funding.

Passive immunoprophylaxis is a class of dietary supplements that is lawfully marketed in the US for maintenance of gut health (GH). This randomized, double-blind, clinical trial will evaluate passive immunoprophylaxis (Travelan®) product compared with placebo, to assess the ability to maintain normal gut function during travel. The results of this clinical trial will be used to evaluate the use of a dietary supplement to maintain GH during deployment and travel and is not intended to support a marketing application of any dietary supplement as a drug or biological product for human use.

This is a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial. The total study duration is 34~36 weeks, including 2-week screening period, 6~8-week dosage titration, 24-week stable treatment and 2-week safety follow-up period. Subjects with obesity or overweight with comorbidity of metabolic disorders receive subcutaneous injection of 3.0 mg Liraglutide or placebo every day. The primary endpoint is the change of body weight or the percentage of body weight loss greater than 5%. The changes of body weight between Liraglutide Injection group and placebo group will be compared. In the course of the trial, the subjects are weighted on fasting state. Blood samples are collected according to the protocol. All subjects receive lifestyle intervention, including a reductiong of calorie intake by 500 kcal a day and physical exercise.

This is a multicenter, randomized, double-blind, placebo controlled trial to evaluate the effect and safety of Liraglutide Injection on body weight loss compared with placebo in obese or overweight adult patients with comorbidity of metabolic disorders.

Liver fibrosis is a key step in the development of various chronic liver diseases (viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune liver disease, etc.) to cirrhosis and an important link that affects the prognosis of chronic liver disease. Fibrosis is histologically reversible, and early liver fibrosis can still be reversed to restore liver tissue to normal. However, due to the lack of specific initial symptoms and accurate non-invasive diagnostic methods, the onset of liver fibrosis is insidious. Most patients have developed liver cirrhosis and/or hepatocellular carcinoma when they are diagnosed, and some even require liver transplantation. If liver fibrosis can be diagnosed accurately and treated early, the prognosis of chronic liver disease can be improved.~Positron Emission Tomography (PET) provides a valuable tool for the diagnosis and staging of liver fibrosis. Activation of hepatic stellate cell (HSC) is a key link in the pathophysiological development of liver fibrosis. In human liver tissue, fibroblast activation protein (FAP) was only expressed in active HSCs and fibroblasts, but not in static HSCs. Therefore, FAP has become an excellent target for diagnosis and treatment of liver fibrosis. Recently, radionuclide-labeled fibroblast activation protein inhibitors (FAPI) as a new novel positron tracer has shown to be effective to detect various cancers. In this prospective study, the investigators will use the most advanced imaging equipments, integrated PET/MR, and PET/CT with gallium-68 (68Ga) -FAPI to image patients with or suspected of liver fibrosis, the aim is to explore the value of 68Ga-FAPI hybrid PET/MR and PET/CT in liver fibrosis.

Positron Emission Tomography (PET) provides a valuable tool for the diagnosis and staging of liver fibrosis. Activation of hepatic stellate cell (HSC) is a key link in the pathophysiological development of liver fibrosis. In human liver tissue, fibroblast activation protein (FAP) was only expressed in active HSCs and fibroblasts, but not in static HSCs. Therefore, FAP has become an excellent target for diagnosis and treatment of liver fibrosis. Recently, radionuclide-labeled fibroblast activation protein inhibitors (FAPI) as a new novel positron tracer has shown to be effective to detect various cancers. In this prospective study, the investigators will use the most advanced imaging equipments, integrated PET/MR, and PET/CT with gallium-68 (68Ga) -FAPI to image patients with or suspected of liver fibrosis, the aim is to explore the value of 68Ga-FAPI hybrid PET/MR and PET/CT in liver fibrosis.

As a serosurveillance measure, 3296 asymptomatic employees of an industrial workforce Jamshedpur (India) were tested for COVID-19 IgG antibodies specific for the spike subunit antigen by the ErbaLisa COVID-19, Erba Corporate Services (United Kingdom) between 28th June and 15th July 2020.~The cases who tested positive for COVID-19 IgG antibodies were repeat tested for the presence of COVID-19 IgG at 45-65 days after initially testing positive. This was done with the aim of finding out the percentage of cases retaining their IgG antibodies at 45-65 days of initially testing positive.

As a serosurveillance measure asymptomatic employees of an industrial workforce Jamshedpur (India) were tested for COVID-19 IgG antibodies. Of the tested employees who were positive for COVID-19 IgG antibodies the study aimed to find the percentage of cases who retained their COVID-19 IgG antibodies 45-65 days after initially testing positive.

The aim of the present study is to test whether brief app-based mindfulness and compassion practices will improve daily psychological stress responses in a sample of adult women (age 30-60) who report a history of early life adversity. The study will incorporate surveys and mindfulness-based intervention practices into everyday life using mobile technology (study app). Participants receive app-notifications three times/day (morning, afternoon, evening) to complete Ecological Momentary Assessments (EMAs) of current psychological stress states (pre-EMA; e.g., stress appraisals, affect, perseverative cognitions, self-criticism, social connection). At each notification, each participant is then randomized to either receive a mindfulness-based intervention (described in detail below) or no intervention. Thus, each participant is randomized many times over this 30-day study (Micro-Randomized Trial, MRT). Psychological stress states are again measured approximately 15 min post-randomization (post-EMA; e.g., stress appraisals, affect, perseverative cognitions, self-criticism, social connection) to assess a treatment effect by comparing psychological stress responses after a mindfulness-based intervention vs. no intervention. The MRT will continue for 30 days. All study participants will be asked to fill out questionnaires at baseline and post-intervention (after 30 days). Weekly measures of depressive symptoms are also obtained. A trained research assistant will monitor participant adherence and address potential difficulties.~Mindfulness-based intervention: The intervention consists of mindfulness and compassion-based practices. For example, practices focus on the breath/body (e.g., 3 minute breathing space; compassionate body scan; five senses mediation), on increasing participants' inner resources (e.g., imaging a safe person or safe place), on reducing negative affect (e.g., self-compassionate and acceptance-based practices), or on increasing positive emotions (e.g., gratitude practice; metta practices). All interventions are brief (≤5 minutes) and audio-guided.

The aim of the Everyday Moments of Mindfulness (EMMI) study is to test whether brief mindfulness-based practices will improve daily psychological stress responses in women (age 30-60) who report a history of early life adversity. Following a baseline visit (remotely or in person), participants complete daily surveys and audio-guided mindfulness-based practices in everyday life via the study app. Specifically, participants receive app-notifications three times/day (morning, afternoon, evening) to complete daily surveys of current stressors and psychological states. At each notification, each participant is then randomly assigned to either receive a mindfulness-based intervention or not (max of 3 interventions/day). Thus, participants are randomized many times over the course of this 30-day study. At the end of the study, participants complete a follow-up visit (remotely or in person).

Decisions about the provision of anticancer therapy and the initiation of palliative care in the last months of life are frequent and challenging in clinical practice. Research indicates that there is considerable heterogeneity regarding clinical practice in this context and that oncologists' values influence treatment decisions, as well as whether or not patients participate in these decisions. While there is evidence that seriously ill patients differ in their choices between treatment options compared to healthy persons, as well as in their evaluation of treatment goals and related care settings, there is a lack of analysis regarding criteria relevant to patients in the last 6 months of life, when assessing the benefit of anticancer treatment and palliative care. Yet, in decisions about anticancer treatment and involvement of palliative care, patients' preferences and values are of particular importance since anticancer treatment - while associated with high expectations for a positive effect - often has only marginal influence on prognosis towards the end of a cancer trajectory and sometimes forestalls choosing a palliative care setting or coping with the disease. Hence, the decision has a high impact on patients' last months of life. Involving patients more actively in the planning of their care has been on the agenda for more than a decade, but the implementation of this idea in routine clinical practice remains a challenge. Instead, oncologists often avoid prognosticating and eliciting patient preferences for or against anticancer treatment and values in the last phase of life. One important reason is that oncologists report discussions about ending anticancer therapy the most challenging communication task.~To support advanced cancer patients, for whom standard therapy is no longer available, and their oncologists in therapy decisions, the investigators aim to develop a decision-making aid (DA) in a multi-phased bicentric study. The DA aims to help patients to understand better risks and benefits of available treatment options including the options of standard palliative care, off-label drug use within an individual treatment plan and involvement in early clinical trials.~Methods and analysis:~In phase I, the DA will be developed after exploration of decisional needs of patients and views of health care providers based on face-to face interviews and focus groups discussions. Subsequently, the DA will be alpha-tested and redrafted, as necessary, in phase II. In phase III, the DA will be (1) beta-tested with patients and oncologists and (2), and assessed by experts. In the last project phase, the investigators will run a pre-post design study with doctor-patient-encounters to access improvements on primary study outcome, i.e. patients' level of decisional conflict. In addition, the user acceptance will be tested.

To support advanced cancer patients, for whom standard therapy is no longer available, and their oncologists in therapy decisions, the investigators aim to develop a decision-making aid (DA) in a multi-phased bicentric study. The DA aims to help patients to understand better risks and benefits of available treatment options including the options of standard palliative care, off-label drug use within an individual treatment plan and involvement in early clinical trials.

This is a multi-center, observational study that will enroll 1) patients with severe COVID-19 who have agreed to undergo therapy with Seraph® 100 under the existing EUA; 2) patients (medical record data) that have been previously treated with the Seraph® 100 after the date of the EUA approval (17 April 2020), but before the date that the study is approved at the study site, and 3) a convenience sample of patients (medical record data) in a historical control group who were admitted to the ICU at participating sites with severe COVID-19 infection, meeting the EUA treatment criteria, but not treated with Seraph® 100 up to the time the PURIFY-OBS protocol is approved at the site~At the time of protocol approval, data from all patients who have been treated up until that date will be collected retrospectively. Patients who meet the treatment criteria and are identified as candidates for Seraph® 100 with plans for treatment initiation will be enrolled prospectively after informed consent has been obtained. Biospecimen collection (blood, urine, sputum, swabs) will be planned for prospectively enrolled patients at various time-points. However, if subjects do not want to contribute samples, they will be given the option of contributing only their clinical data for analysis. Specific Seraph® 100 treatment procedures will be determined by each individual site. Recommendations for treatment related procedures are provided by the company. Additionally, among sites participating in PURIFY-OBS, all patients who met EUA treatment criteria but were NOT initiated on therapy will be enrolled retrospectively into a historical control group. Procedures for identifying study subjects will be as follows:~Retrospective Seraph® 100 As noted in the inclusion/exclusion criteria, this group will be composed of subjects that were treated with Seraph® 100 after the date of the EUA approval (17 April 2020), but before the date that the study is approved at the study site. To identify patients, the site investigator will query 1) institution's electronic medical record for critical ill patients treated with Seraph® 100 and 2) attending intensive care physicians and nephrologists who have provided care to critically ill patients with COVID-19. A waiver of informed consent will be requested from the Institutional Review Board (IRB) to allow the collection of these retrospective data.~Prospective Seraph® 100 To identify prospective Seraph® 100 patients, the individual site investigators will review currently admitted ICU patients for inclusion criteria #1and #2 (see above). The study team will then ask the physician caring for the patient to contact the study team should the patient require therapy with Seraph® 100. Additionally, the study team will review the medical records of admitted patients to see if they have recently been started on Seraph. Patients found to meet inclusion/exclusion criteria (or their LARs) will be offered the opportunity to sign an informed consent and participate in the study. Note that patients that were started on Seraph® 100 before the date of approval for a study site, but are still admitted, will not be eligible to give biospecimens. However, they will be given the option of signing an informed consent so that their data can be used in the study.~Historical Control Our historical control group will be a sample of convenience, composed of patients admitted to the ICU at participating sites with severe COVID-19 infection, meeting the EUA treatment criteria, but not treated with Seraph® 100 up to the time the PURIFY-OBS protocol is approved at the site. The individual site investigators will be responsible for querying their institution's electronic medical records to identify critically ill patients with COVID-19 admitted from the date of EUA approval (17 April 2020) until the date the protocol was approved at their study site. These records will then be further examined by the local study team to ensure that the patients meet the inclusion/exclusion criteria detailed above. Note that patients will be excluded if they are still admitted to the hospital on or after the date that the protocol was approved at that study site. A waiver of informed consent will be requested from the Institutional Review Board (IRB) to allow the collection of these retrospective data.~Study Timeline Each included subject's medical record will be reviewed from the time of hospital admission through hospital discharge. Enrollment will be conducted over a 2-year period (up to 200 patients total including both retrospective and prospective patients). For prospective patients who consent, biospecimen (blood, urine, sputum) will be collected before initiation of extracorporeal treatment, 1 hour following treatment, as well as days 1, 2, 3, 4, 7, 28 and 90-180

This is a multi-center, observational study that will enroll 1) patients with severe COVID-19 who have agreed to undergo therapy with Seraph® 100 under the existing EUA; 2) patients (medical record data) that have been previously treated with the Seraph® 100 after the date of the EUA approval (17 April 2020), but before the date that the study is approved at the study site, and 3) a convenience sample of patients (medical record data) in a historical control group who were admitted to the ICU at participating sites with severe COVID-19 infection, meeting the EUA treatment criteria, but not treated with Seraph® 100 up to the time the PURIFY-OBS protocol is approved at the site

50 females will be included in this study. they will be divided into 2 groups (study group which will include 25 postmenopausal females - and control group which will include premenopausal females)~For testing gustatory function, a whole mouth above threshold taste test will be carried out in which a concentration of sucrose, sodium chloride, citric acid and quinine hydrochloride solutions were used for sweet, salty, sour and bitter types of taste respectively . Five concentration levels (in ½ log steps) of sodium chloride (0.01-1.0 mM), citric acid (0.32-0.032 mol l-1), quinine hydrochloride (0.01- 1.0 mM) and sucrose (0.01-1.0 mM) will be prepared in 5 ml samples. All the solutions will be made with distilled water. The intensity threshold of taste perception of each solution will be determined by scoring the lowest concentration as 5' and the highest concentration as 1'. The solutions will be given in increasing concentrations. The patient then should identify the quality (salty, sour, sweet, bitter or tasteless) and intensity of each test solution . Quality judgments for each solution will be coded as correct, incorrect or tasteless by asking subjects to name the taste they perceived.~Saliva will be collected in the morning between 9:00 am and 11:00 am. Patient will be instructed to stop eating and drinking at least 2 h before sample collection. Chewing 1 g of gum base will be used to stimulate salivary flow. The saliva that will be collected for the first 2 min will be discarded, and then Stimulated whole saliva will be collected for the next 10 min with the mechanical chewing stimulation.~Two milliliters of Stimulated whole saliva from each participant will be collected and added to RNA stabilizing solution and used for RNA extraction. The SWS samples will be centrifuged at 10,000 g for 20 min at 48C to remove any cellular debris. The clarified supernatants will be aliquoted and frozen at 70 C for analytic experiments.~this is to determination of oral mucosal epithelial MUC1 expression level

50 females will be included in this study. they will be divided into 2 groups (study group which will include 25 postmenopausal females - and control group which will include premenopausal females) For testing gustatory function, a whole mouth above threshold taste test will be carried out in which a concentration of sucrose, sodium chloride, citric acid and quinine hydrochloride solutions were used for sweet, salty, sour and bitter types of taste respectively .~Saliva will be collected to evaluate MUC1 expression

This first-in-human (FIH) study will investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SLN360 after single ascending s.c. doses and multiple doses in healthy male and female subjects.~Up to 9 cohorts of 88 patients with elevated Lp(a) will be enrolled. Each patient will receive single or multiple doses of SLN360 or placebo given by subcutaneous (s.c) injection.

This study will investigate the safety and tolerability of SLN360 in patients with elevated Lp(a).

The hemi paretic arm is one of the most undesirable consequences of stroke. Approximately 30-66% of patients with stroke are not able to gain motor function of their affected hand which prevents them from performing their daily activities for the rest of their lives.The paralysis of upper limb along with increase in muscle spasticity, muscle weakness and loss of sensory perception are reasons of disability in stroke patients. It is very important in the treatment of stroke patients to make effective treatment strategies to improve their upper limb function. Many treatment options are used for the recovery of upper limb motor function such as robot-assisted therapy and constraint induced movement therapy. Mirror therapy has drawn much focus for the rehabilitation of hemiplegic stroke patients in the past two decades. Mirror therapy is one of the priming technique that causes neural plasticity of brain.Mirror therapy is also used to address problems like phantom limb pain.In stroke patients it is helpful in managing pain and hemi spatial neglect. According to the theory the cortical areas of brain that are involved in the motor task execution can be activated by observing the actions performed by others, which is the function of the mirror neuron system (MNS).The mirror neuron system is composed of mirror neurons that discharge during action observation (AO) and action execution. The mirror neuron system is located in the inferior frontal gyrus (IFG), including the ventral premotor cortex (PMv), the inferior parietal lobule (IPL), and the intraparietal sulcus (IPS). It also extends to other brain areas like the primary motor cortex, the primary somatosensory cortex, and the middle frontal cortex. In mirror therapy we use the mirror neuron system to perform action observation training (AOT) and action execution.~In mirror therapy a mirror is placed in the mid sagittal plane of a patient between the two arms and the patient is given instruction to move his less affected or normal limb while looking at its reflection in the mirror which will produce as the affected or paretic limb is also moving with a normal movement pattern.This will create visual stimulus on the patient's brain known as mirror visual feedback (MVF) and will cause cortical reorganization hence it will increase the motor recovery of the affected or paretic limb.~The scales that have been used in previous studies to measure motor recovery and improvement in daily functions of stroke patients with mirror therapy are Brunnstrom stages of recovery, Fugl-Meyer assessment (FMA) and Functional Independence Measure (FIM).The findings of these studies has shown positive effects of mirror therapy on decreasing motor impairment.~Conventional mirror therapy that is most commonly used involves simple movements performed by unaffected arm like wrist extension flexion, fingers flexion extension and forearm supination and pronation while looking at the visual stimulus created by the mirror placed at their mid sagittal plane.~The functional task-oriented training is mostly used intervention for bringing beneficial neural plasticity and improving paretic upper limb functional performance. Functional task-oriented training recently applied on stroke patients has proven to be more effective than the conventional therapy. A type of mirror therapy is task based mirror therapy in which the participants are asked to perform specific motor tasks with their less affected arm. Functional tasks may include flipping a card, holding a polystyrene cup, squeezing a sponge. A research was carried out in Korea to determine the effects of mirror therapy with functional tasks on upper limb function and activities of daily living in patients with subacute stroke. The patients were randomly divided into two groups the mirror therapy group and the control group.The Fugl-Meyer Motor Function Assessment (FMA), Brunnstrom motor recovery stage, and Modified Barthel Index (MBI) were assessed 4 weeks after the treatment and the results were significantly greater in the mirror therapy group than the control group.~A study was conducted to determine the effectiveness of mirror therapy in chronic stroke patients with severe dysfunction of upper limb and its comparison was done with the control group. The results showed significant improvements in mirror therapy group regarding motor recovery and tactile stimulation.~Another study done b to determine if a mirror therapy-based action observation (AO) protocol contributes to motor learning of the paretic arm in post stroke patients.The outcome measure of this study was movement time of the reaching movement which was measured by accelerometry. The results showed that the decrease in movement time was much more in the action observation group as compared to the control group. Thus the study showed that a mirror therapy based action observation protocol contributes more to motor learning in post stroke patients.~another study which was the first to achieve delayed mirror visual feedback (MVF) for upper extremity mirror therapy training. Their results support the positive effects of mirror visual feedback on the cortical activation of brain and hence give additional evidence supporting the use of mirror therapy in the future for upper-limb motor training in patients with stroke.~A systematic review was done to evaluate the activation of the mirror neuron system (MNS) during the action observation and action execution training with mirror visual feedback (MVF) in post stroke patients. The effect of activation of motor cortex of brain in stroke patients with mirror therapy was also determined. The results showed that the MVF may cause stroke recovery by revising the interhemispheric imbalance caused by stroke and also cause the activation of the MNS. Action observation training also promoted motor relearning in stroke individuals by the activation of the MNS and the motor cortex.~Another systematic review was done to conclude the effects of mirror therapy for improving motor functions and decreasing motor impairment after stroke. They also assessed the effects of mirror therapy on the activities of daily living of stroke patients. The results gave evidence on the effectiveness of mirror therapy for increasing upper limb motor function, decreasing motor impairment, improving their activities of daily living and decreasing their pain as compared to the conventional rehabilitation for stroke patients.

The hemiparetic arm is one of the most undesirable consequences of stroke. Approximately 30-66% of patients with stroke are not able to gain motor function of their affected hand which prevents them from performing their daily activities for the rest of their lives. It is very important in the treatment of stroke patients to improve their upper limb function. Mirror therapy has drawn much focus on the rehabilitation of hemiplegic stroke patients in the past two decades. Mirror therapy is one of the priming technique that causes neural plasticity of the brain. In mirror therapy a mirror is placed in the mid-sagittal plane of the patient between his two arms and the patient is given instruction to move his less affected or normal limb while looking at its reflection in the mirror which will produce as the affected or paretic limb is also moving with a normal movement pattern. This will create visual stimulus on the patient's brain known as mirror visual feedback (MVF) and will cause cortical reorganization hence it will increase the motor recovery of the affected or paretic limb. A type of mirror therapy is task-based mirror therapy in which the participants are asked to perform specific motor tasks with their less affected arm. There are very few studies regarding mirror therapy combined with functional tasks. It is a randomized controlled trial study and its duration is 6 months. Total sample size will be 26; 13 participants into each group. The subjects will be divided into two groups, Group A Experimental group and Group B control group. A 20 minutes session will be performed thrice in a week for a total of 6 weeks. The experimental group will perform functional tasks with mirror therapy and the control group will perform functional tasks without mirror therapy. The Standardized Mini-Mental State Examination scale and Brunnstrom stages of motor recovery scale will be used in the inclusion criteria of patients. Outcomes of patients will be measured using Brunnstrom stages of motor recovery, Motor Assessment Scale (MAS) upper limb component, Fugl Meyer Upper Extremity Assessment Scale (FMA-UE) and Functional Independence Measure (FIM) self-care component at baseline, after every 2 weeks and with follow up at 6 weeks. After this, the data will be analyzed on the Statistical Package for the Social Sciences (SPSS) 21 version.

A common goal of the health professions is to keep the elderly functional, preventing sarcopenia and frailty. Is there an association between handgrip strength in partially edentulous elderlies after completing their dentition with removable partial dentures?

A common goal of the health professions is to keep the elderly functional, preventing sarcopenia and frailty. Is there an association between handgrip strength in partially edentulous elderlies after completing their dentition with removable partial dentures?

Resistance to EGFR-TKIs is a clinical problem. One of the mechanisms for resistance to osimertinib is amplification of the MET receptor tyrosine kinase, which activates downstream intracellular signalling independent of EGFR. This study will explore the individual contribution of savolitinib to MET mediated osimertinib resistance, by assessing the response to dual pathway blockade of EGFRm and MET to overcome MET mediated resistance to osimertinib versus inhibition of the MET pathway alone by investigating the efficacy of savolitinib plus osimertinib versus savolitinib plus placebo to osimertinib (hereafter referred to as placebo) in patients with EGFRm+ and MET amplified, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib. This is a multi centre, Phase II, double blind, randomised study.~Patients will be randomised in a ratio of 1:1 to receive treatment with savolitinib once daily plus osimertinib once daily or savolitinib once daily plus placebo. Randomisation will be stratified according to the number ofprior lines of therapy (ie, osimertinib monotherapy as first line or ≥ second line [which includes patients who received osimertinib monotherapy before or after chemotherapy]). All patients confirmed as eligible will begin treatment on Day 1 with savolitinib plus osimertinib or savolitinib plus placebo. Treatment will continue once daily in 28 day cycles until either objective PD by RECIST 1.1 is assessed, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.~After progression, patients can be unblinded, and patients initially randomised to the savolitinib plus placebo arm may cross-over to open-label savolitinib plus osimertinib following investigator assessed objective PD to ensure that all patients enrolled may have the opportunity to receive the combination of savolitinib plus osimertinib.

This study will compare the activity of the combination of savolitinib and osimertinib against the combination of savolitinib with placebo to osimertinib in patients with Epidermal Growth Factor Receptor Mutation Positive and MET amplified, locally advanced or metastatic non-small cell lung cancer who have progressed following treatment with osimertinib.

This multi-centre study funded by Oticon Medical AB will be conducted at seven hospitals across Europe (UK, Sweden, Denmark and the Netherlands). In total, 50 adult patients with a hearing loss that are already planned for treatment with a percutaneous (through the skin) bone-anchored hearing system (BAHS) will be included in the study.~The purpose of the study is to investigate the rate of successful BAHS use after implantation of the Ponto implant system using a minimally invasive surgical technique. The implant, coupled to a skin-penetrating abutment, is implanted in the bone behind the ear and is later loaded with a sound processor which transforms sound waves to sound vibrations that can be sent directly to the inner ear via the skull bone. The primary objective of this study is to investigate the proportion of implant/abutment complexes providing a reliable anchorage for a sound processor three months after implantation/surgery.

This multi-centre study funded by Oticon Medical AB will be conducted at seven hospitals across Europe (UK, Sweden, Denmark and the Netherlands). In total, 50 adult patients with a hearing loss that are already planned for treatment with a percutaneous (through the skin) bone-anchored hearing system (BAHS) will be included in the study.~The purpose of the study is to investigate the rate of successful BAHS use after implantation of the Ponto implant system using a minimally invasive surgical technique.

This Phase 2, open-label study is designed to examine the efficacy and safety of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 in patients with recurrent, inoperable or metastatic AS.~Three cohorts will be enrolled into 2 Parts of the study as follows:~Part 1~Cohort 1: Qualifying patients that are checkpoint inhibitor naïve will be enrolled into single-agent AGEN2034~Cohort 2: Qualifying patients that are inhibitor (PD-1/L1) resistant will be enrolled into combination AGEN2034 + AGEN1884~Part 2~• Cohort 3: Qualifying patients that are checkpoint inhibitor naïve will be enrolled into combination AGEN2034 + AGEN1884. Part 2 will begin enrollment after enrollment in Part 1 is completed~The study will be conducted in 2 parts:~In Part 1, checkpoint inhibitor naïve patients will be treated with single-agent AGEN2034 (Cohort 1) and patients resistant to PD-1/PD-L1 (defined as prior progression on PD 1/PD-L1 treatment) will be treated with combination of AGEN2034+AGEN1884 (Cohort 2). Patients from Cohort 1 who experience PD may be considered (as PD-1 resistant) for transition to Cohort 2.~In Part 2, the study will enroll checkpoint inhibitor naïve patients for treatment with combination AGEN2034+AGEN1884 (Cohort 3). Part 2 will begin enrollment after enrollment in Part 1 is completed.~All patients will receive study treatment for up to 2 years until confirmed disease progression, unacceptable toxicity, or until the patient wishes to withdraw consent for any reason. Patients will be followed for safety at 30 and 90 days, and for survival every 2 months for at least 12 months from their last dose of study treatment. Each treatment cycle will be 6 weeks.~An IRC will be established to adjudicate tumor response based on imaging studies, photography, and clinical response. The primary endpoints will be based on the IRC assessment of response per RECIST v1.1.

This Phase 2, open-label study is designed to examine the efficacy and safety of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 in patients with recurrent, inoperable or metastatic Angiosarcoma (AS).

This study will compare the acute effects of respiratory-gated transcutaneous vagus nerve stimulation (tVNS) at different stimulation frequencies and sham stimulation during five sessions within a 2 week period. Heart rate variability (HRV) point process adaptive filtering estimation algorithms will be used to evaluate changes in cardiac autonomic physiology in subjects with major depression in response to tVNS. The effects of tVNS on cardiovagal regulation will be evaluated at rest and in response to an emotion reactivity task. Depression rating scales (Beck's Depression Inventory) will be used to evaluate short term effects of tVNS on depressive symptoms in these subjects. In addition, the study will evaluate the acute effects of the stimulation on serum levels of pro-inflammatory cytokines. The stimulation frequency that produces the greatest regulatory effects on depressive symptoms and physiological variables in this population will be used in a second longitudinal phase of the study.

This study will evaluate the short term effects of respiratory-gated transcutaneous vagus nerve stimulation on the regulation of cardiovagal activity, depressive symptomatology and immune function in subjects with major depression and determine the optimal stimulation frequency for this population.

Whether metformin could improve the effect of progestin as fertility-sparing treatment in patients with atypical endometrial hyperplasia(AEH) is still not clear. Our previous finding from subgroup analysis in a phase II randomized controlled trial showed that 39.6% of AEH patients in metformin plus megestrol acetate group achieved complete response, compared with 20.4% in group of megestrol acetate alone. This trial aim to fully testify the effect of metformin in fertility-sparing treatment for AEH patients with adequate sample size.

To verify whether metformin could improve the effect of progestin as fertility-sparing treatment in patients with atypical endometrial hyperplasia(AEH).

Fifty-three, fibromyalgia syndrome participants were randomized to receive either: 1) probiotic 4×1010 CFUs per day 2) 10 g dose prebiotic (inulin) per day or 3) placebo for 8 wk. Fibromyalgia Impact Questionnaire (FIQ), Visual Analogical Pain Scale (VAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Pittsburg Sleep Quality Index (PSQI) and quality of life (SF-36) were measured during the baseline, 4 weeks and 8 weeks intervention phases. Finally, the adverse effects will be evaluated.

The aim of the present study is to determine the effectiveness of probiotic and prebiotic treatments in patients with fibromyalgia syndrome.

Increased protein needs are frequently observed in disease and can be difficult for patients to achieve where oral food intake is compromised.Where a standard ONS or enteral tube feed cannot meet the needs of patients, a modular feed can be added to the regimen, a low calorie, low volume, ready to use, high protein liquid may help meet protein needs while preventing caloric overfeeding.~40 patients will be recruited in an attempt to evaluate the acceptability (compliance, gastrointestinal tolerance, and palatability) to a low calorie, low volume, ready to use, high protein liquid in patients with elevated protein needs. After a 1-day baseline period to establish patients' acceptability, gastrointestinal tolerance, compliance and dietary intake with their currently prescribed nutritional regimen, each patient will receive the high protein liquid feed daily for 28 days.

The aim of this prospective, single-arm intervention study is to evaluate the acceptability (compliance, gastrointestinal tolerance, and palatability) to a low calorie, low volume, ready to use, high protein liquid in patients with elevated protein needs.

This study will evaluate the safety and immune response in healthy HIV-exposed and uninfected infants to the protein vaccine, CH505TF gp120, adjuvanted with GLA-SE.~This study will enroll 38 mother-infant pairs. To quantify the maternal HIV antibody response, mothers will also be enrolled in the study but will not receive study product. Infants will receive the CH505TF gp120 protein adjuvanted with GLA-SE at Weeks 0, 8, 16, 32, and 54. The first dose will be given within the first five days of life.~The study will be conducted in three parts (Parts A, B, and C), and to ensure safety, enrollment will proceed in stages.~Part A (Initial Safety) will enroll first. 5 infants in Part A will receive a low dose of protein with a low dose of adjuvant and 2 infants will receive placebo.~After safety review post first vaccination of infants in Part A, Part B will enroll. In Part B (Safety Ramp-Up), 2 infants will receive a higher dose of protein with a higher dose of adjuvant and 2 infants will receive placebo.~After safety review post first vaccination of infants in Part B, Part C will enroll. In Part C (Immunogenicity), 5 infants will receive low dose protein with higher dose of adjuvant, 16 infants will receive a higher dose of protein with higher dose of adjuvant, and 6 infants will receive placebo.~There are 14 scheduled clinic visits over 24.5 months. For infants, study visits may include physical examinations, medical history, vaccine injections, HIV testing, and blood, cord blood, and stool collection. For mothers, study visits may include medical history, physical examinations, questionnaires, risk reduction counseling, and blood, breastmilk, and stool collection.

This study will evaluate the safety and immune response in healthy HIV-exposed and uninfected infants to the protein vaccine, CH505TF gp120, adjuvanted with GLA-SE.

1. Literature basis cute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by respiratory distress and progressive hypoxemia, which is caused by diffuse alveolar and pulmonary interstitial edema caused by various pulmonary and extrapulmonary factors other than cardiogenic factors. ARDS incidence rate is as high as 75 /10 000 per year, and sepsis and pulmonary infection are the most common causes. In the past, it was generally believed that excessive immune activation is the core of the pathophysiology of ARDS, and neutrophils are recognized as the core driver of inflammatory hyperactivity and lung injury in ARDS. Although some progress has been made in the epidemiology, pathogenesis and pathophysiology of ARDS in the past 50 years, and the clinical outcomes of some patients with ARDS have been improved by optimizing the mode of mechanical ventilation and fluid treatment, as well as prone ventilation and the use of muscle relaxants, ARDS is still one of the most common causes of death and disability in intensive care units, The mortality rate of the disease is currently as high as 30-40%. There is still a lack of effective drugs for the treatment of ARDS in clinic, and even glucocorticoids applied for immune overactivation have not achieved good results. This is related to the unclear pathogenesis of ARDS. Therefore, it is still a hot and difficult point to further explore the pathogenesis and progression of ARDS and find new therapeutic targets.~In the past, mature PMN in peripheral blood was generally considered as a functional cell in the end stage, but it is widely involved in different innate immune responses (including inflammation, infection, tumor, autoimmunity, etc.) and can adopt very different effector mechanisms. Therefore, with the deepening of research, neutrophil subtypes with different functions (such as immune regulation and repair) have been identified in recent years: cd16dimcd62lbrightpmn and cd16brightcd62ldimmpmn. In the steady state of healthy people, the classic mature neutrophils (cd16brightcd62lbright) in peripheral blood account for more than 98% of the total PMN, and the proportion of the two neutrophil subtypes is relatively low. In the inflammatory state, the proportion of cd16dimcd62lbright and cd16brightcd62ldim neutrophils increased significantly. Proteomic analysis showed that there were significant differences between the two subtypes of neutrophils. The nucleus of cd16dimcd62lbright neutrophil subgroup is banded, which is released from bone marrow after being stimulated by lipopolysaccharide (LPS). It accounts for 20% - 25% of PMN in whole blood in LPS infection model. The apoptosis rate is significantly reduced, and the bacteriostatic effects such as oxidative burst and phagocytosis are significantly enhanced; On the contrary, cd16brightcd62ldim neutrophil subgroup has reduced antibacterial ability and shows immunosuppressive phenotype. It is a newly discovered neutrophil subtype with immunosuppressive function in recent years, which can inhibit T cell proliferation, which is related to immunosuppression in the experimental human endotoxemia model.~In our previous studies, we have successfully obtained a new amino acid derivative of ocotillol ginsenoside, which may have the pharmacological activities of ocotillol ginsenoside and glycine, and has a potential role in improving the delay of apoptosis and immunosuppression of ARDS neutrophil subtypes, and has the potential of new drug development for the treatment of ARDS.~2. The experimental steps are as follows:~Peripheral blood samples from patients with ARDS were collected to detect inflammatory markers;~Neutrophils were isolated from peripheral blood of patients with ARDS;~The proportion of neutrophil subtypes was detected by flow cytometry, and the neutrophil subtypes were isolated;~Neutrophil subtypes were co cultured with peripheral blood T lymphocytes to detect their ability to inhibit T cell proliferation and the apoptosis of neutrophil subtypes;~Peripheral blood neutrophils and different doses of ginsenoside glycine derivatives in patients with ARDS (2050100 μ m) After incubation for 20h, the apoptosis rate was 28h.~Bax, Mcl-1 and cleaved caspase-3 were detected by Western blot.~High throughput PCR and mapp-4 were used to detect the expression of apoptosis related genes in akg38k pathway.~Metabolomic analysis: collect the peripheral blood of ARDS patients for metabolomic analysis.~3. Research methods~Diagnostic criteria: refer to the 2012 Berlin standard for the diagnostic criteria of ARDS.~Inclusion criteria: (1) age ≥ 18 years old; (2) Diagnosis of acute lung injury within 24 hours (Berlin diagnostic criteria for acute lung injury)~Exclusion criteria: (1) age < 18 years; (2) Discharge or death within 48 hours after admission; (3) Pregnancy or puerperium; (4) Patients with immunosuppression.~4. Test procedure~Methods: ICU patients who met the inclusion criteria were selected~Informed consent process: sign the informed consent form after communicating with the patient or legal representative~5. Start and end of the experiment Informed consent was signed in January 2020~6. Data security and monitoring plan The patient's medical records (study medical records / CRF, test forms, etc.) will be kept completely in the hospital. The doctor will record the results of laboratory tests and other examinations in his medical record. The researchers, the ethics committee and the drug administration will be allowed access to his medical records. No public report on the results of the study will reveal the individual identity of the patient. We will make every effort to protect patient information to the extent permitted by law. According to medical research ethics, except for personal privacy information, experimental data will be available for public inquiry and sharing, and the query and sharing will be limited to the electronic database based on the network to ensure that no personal privacy information will be disclosed.~7. Abide by ethical principles and relevant laws and regulations Whether or not to participate in the study depends entirely on the wishes of patients and their legal representatives. Patients and their families may refuse to participate in the study or withdraw from the study at any time during the course of the study. This will not affect the relationship between the patient and his doctor, nor will it affect the loss of medical or other benefits for the patient.~8. Statistical analysis plan SPSS15.0 software was used for statistical analysis. The measurement data were expressed as mean ± standard deviation, t test or nonparametric test was used for comparison between groups, chi square test was used for counting data, and linear correlation analysis was used for the relationship between variables, P < 0.05 was considered as statistically significant.

Literature basis Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by respiratory distress and progressive hypoxemia, which is caused by diffuse alveolar and pulmonary interstitial edema caused by various pulmonary and extrapulmonary factors other than cardiogenic factors. ARDS incidence rate is as high as 75 /10 000 per year, and sepsis and pulmonary infection are the most common causes. In the past, it was generally believed that excessive immune activation is the core of the pathophysiology of ARDS, and neutrophils are recognized as the core driver of inflammatory hyperactivity and lung injury in ARDS. Although some progress has been made in the epidemiology, pathogenesis and pathophysiology of ARDS in the past 50 years, and the clinical outcomes of some patients with ARDS have been improved by optimizing the mode of mechanical ventilation and fluid treatment, as well as prone ventilation and the use of muscle relaxants, ARDS is still one of the most common causes of death and disability in intensive care units, The mortality rate of the disease is currently as high as 30-40%. There is still a lack of effective drugs for the treatment of ARDS in clinic, and even glucocorticoids applied for immune overactivation have not achieved good results. This is related to the unclear pathogenesis of ARDS. Therefore, it is still a hot and difficult point to further explore the pathogenesis and progression of ARDS and find new therapeutic targets.~In the past, mature PMN in peripheral blood was generally considered as a functional cell in the end stage, but it is widely involved in different innate immune responses (including inflammation, infection, tumor, autoimmunity, etc.) and can adopt very different effector mechanisms. Therefore, with the deepening of research, neutrophil subtypes with different functions (such as immune regulation and repair) have been identified in recent years: cd16dimcd62lbrightpmn and cd16brightcd62ldimmpmn. In the steady state of healthy people, the classic mature neutrophils (cd16brightcd62lbright) in peripheral blood account for more than 98% of the total PMN, and the proportion of the two neutrophil subtypes is relatively low. In the inflammatory state, the proportion of cd16dimcd62lbright and cd16brightcd62ldim neutrophils increased significantly. Proteomic analysis showed that there were significant differences between the two subtypes of neutrophils. The nucleus of cd16dimcd62lbright neutrophil subgroup is banded, which is released from bone marrow after being stimulated by lipopolysaccharide (LPS). It accounts for 20% - 25% of PMN in whole blood in LPS infection model. The apoptosis rate is significantly reduced, and the bacteriostatic effects such as oxidative burst and phagocytosis are significantly enhanced; On the contrary, cd16brightcd62ldim neutrophil subgroup has reduced antibacterial ability and shows immunosuppressive phenotype. It is a newly discovered neutrophil subtype with immunosuppressive function in recent years, which can inhibit T cell proliferation, which is related to immunosuppression in the experimental human endotoxemia model.~In our previous studies, we have successfully obtained a new amino acid derivative of ocotillol ginsenoside, which may have the pharmacological activities of ocotillol ginsenoside and glycine, and has a potential role in improving the delay of apoptosis and immunosuppression of ARDS neutrophil subtypes, and has the potential of new drug development for the treatment of ARDS.~The experimental steps are as follows:~Firstly, the peripheral blood of ARDS patients in ICU was collected, and neutrophils were isolated from the peripheral blood. The proportion of neutrophil subtypes and the degree of apoptosis were detected by flow cytometry. Co culture with human T lymphocytes in vitro to observe its ability to inhibit T cell proliferation. Then, the neutrophils of ARDS patients were cultured with different doses of ginsenoside glycine derivatives, and the detection of the above indexes was repeated again. Finally, the mechanism of neutrophils in the pathogenesis and progression of ARDS was discussed.

Painful symptomatic osteoarthritis (OA) of the knee is a very common disease, especially in older people (lifetime prevalence 9.5%). Current systemic pharmacological treatment options are limited. The Osteoarthritis Research Society International recommends paracetamol, duloxetine, oral non-selective non-steroidal anti-inflammatory drugs and oral COX-2 inhibitors (anti-inflammatory substances) in patients without relevant concomitant diseases. In individuals with relevant concomitant diseases (diabetes, advanced age, high blood pressure, cardiovascular diseases, renal failure, gastrointestinal complications, depression, obesity), the recommendation for paracetamol, oral non-selective non-steroidal anti-inflammatory drugs and oral COX-2 inhibitors changes to 'inappropriate'.~In individuals with high co-morbidity risk (history of GI-bleeding, myocardial infarction, chronic renal failure) NSAIDs and oral COX-2 inhibitors are evaluated as inappropriate.~Many patients presenting with knee osteoarthritis are of an advanced age and suffer from various co-morbidities. The benefit of the available systemic pharmacological treatment options in these patients can be summarized as uncertain. Therefore, the investigation of new symptomatic systemic pharmacological treatment options for knee OA is relevant. Even in patients without known contraindications, the treatment period with non-steroidal anti-inflammatory drugs should be kept short. It follows that the investigation of new potentially anti-inflammatory substances is of interest in symptomatic OA of the knee.~Design~The planned study will be randomised, double-blind and placebo-controlled. 2 parallel groups will be investigated. One group will receive placebo, the other will receive 600mg cannabidiol per os during the treatment phase. The total study duration will be 13 weeks (2 weeks screening;~1 week titration phase; 7 weeks maintenance phase; 1 week tapering phase; 2 weeks follow-up) Main objective of the study will be to compare the change in the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain Index from baseline to the last week of the maintenance phase between the placebo and verum groups. The WOMAC Osteoarthritis Index is a validated patient questionnaire to assess symptoms and physical functional limitations in everyday life.~Secondary objectives include comparing the change in the WOMAC Function Index, the Global Patient Assessment of Gonarthrosis and the VAS Score. The planned number of participants is 86 (43 patients per group)~Measures/procedure After a 2-week screening phase, patients are randomised to a 1:1 placebo:verum after written consent. During the screening all patients are adjusted to a basic medication of 3 times 1g paracetamol/day. In the cannabidiol arm, titration is carried out within one week to the target dose of 600mg per day. This dosage is maintained for 7 weeks. This is followed by a balancing phase of 1 week. A follow-up is carried out 2 weeks after the maintenance phase is finished.~4 study visits are associated with blood sampling (safety laboratory) and physical examination and the completion of questionnaires and are carried out at our pain outpatient clinic. The remaining weekly visits are carried out by telephone.~During the entire duration of the study, patients are allowed the rescue medication of Tramadol 50mg up to 6/day.

Painful symptomatic osteoarthritis (OA) of the knee is a very common disease, especially in older people (lifetime prevalence 9.5%). Current systemic pharmacological treatment options are limited.~Many patients presenting with knee osteoarthritis are of an advanced age and suffer from various co-morbidities. The benefit of the available systemic pharmacological treatment options in these patients can be summarized as uncertain. Therefore, the investigation of new symptomatic systemic pharmacological treatment options for knee OA is relevant. Even in patients without known contraindications, the treatment period with non-steroidal anti-inflammatory drugs should be kept short. It follows that the investigation of new potentially anti-inflammatory substances is of interest in symptomatic OA of the knee.~Cannabidiol has anti-inflammatory and analgesic properties in animal models. We therefore propose a randomised, double-blind, placebo-controlled clinical trial to investigate the potential efficacy of cannabidiol in painful symptomatic OA of the knee.

The purpose of this study is to assess the effect of Interactive Guidance Therapy with video feed back (IGT) of parent and child with Autism Spectrum Disorder, under three years of age, using a Single Case Experimental Design.~Early Interventions in Autism Spectrum Disorders (ASD) undergo a major development. The investigators identify three generations of early support: 1) Behavioral studies ; 2) Early Intensive Behavioral Interventions (EIBI), inspired by ABA, focused on targeted ASD disorders 3) Naturalistic Behavioral Developmental Behavioral Interventions (NDBI), more ecological, focused on the child's skills.~Among them, methods of video feedback target parental sensitivity (identification, interpretation, response, contingency and synchrony). The VIPP (Video Interactive Positive Parenting) in children less than one year of age, has shown moderate and long term effects on parent-child interaction. The PACT (Preschool Autism Communication Trial) showed immediate and in the long term effects on the synchronization of the parental response, the child initiation, less importantly on the joint attention, and on the autistic symptoms. The dyadic communication allows for changes in autistic symptoms.~Interactive guidance is a brief video-feedback therapy, based on the analysis of the here and now with the parent (s), of videotaped interactions with their child. The objective is to strengthen parental skills, their sensitivity, their ability to decipher and respond to the specific needs of their child.~The interest of IGT in the field of ASD, compared to VIPP and PACT, is to offer a standardized feedback intervention adapted to each dyad, according to the child's and parents skills and difficulties, structured on the here and now more than on a predetermined sequence of goals.~The investigators use the Single Case Experimental Design (SCED) with multiple baseline across subjects, multicentric, randomized, with multiple replications, blinded scored.~They expect~to improve the interactive and communicative basic skills of the child, soon after the ASD diagnosis, by accompanying the parents in the identification and understanding of their child's disorders.~to propose a method highlighting parental skills, in a collaborative and pleasant way~To increase the parental alliance in the implementation of a tailored intervention for the child~To facilitate access to healthcare and reduce the parental wandering in the implementation of intervention

The purpose of this study is to assess the effect of Interactive Guidance Therapy with video feed back (IGT) of parent and child with Autism Spectrum Disorder, under three years of age, using a Single Case Experimental Design (SCED) with multiple baseline across subjects, multicentric, randomized, with multiple replications, blinded scored

DAHANCA 35 is two parallel conducted, but separate randomized studies, within the same trial (DAHANCA 35D and DAHANCA 35X) by the Danish Head-Neck Cancer Study Group (DAHANCA). In patients with squamous cell carcinoma of the pharynx or larynx planned for primary radiotherapy a proton and a photon doseplan is prepared. If proton radiotherapy reduces the anticipated absolute risk of dysphagia >= grade 2 (DAHANCA scale, DAHANCA 35D) or severe xerostomia >= grade 4 (EORTC Head-Neck 35, DAHANCA 35X) more than 5%, the patient is randomised to either proton therapy or photon therapy, 2:1. The anticipated risk of xerostomia and dysphagia is estimated using Normal-Tissue Complication Models (NTCP). Patient are analysed according to the primary endpoint (dysphagia and/or xerostomia) after which they were enrolled. DAHANCA 35D is expected to enroll 360 patients and DAHANCA 35X 240 patients (in total 600 patients).

Patients with squamous cell carcinoma of the pharynx or larynx and an anticipated benefit of proton radiotherapy in reducing the risk of late dysphagia or xerostomia are randomized to proton or photon radiotherapy (2:1)

Foot disorders have been recognized as being linked to chronic low back pain (CLBP), To improve knowledge of the relationship between the limitation of the movement range of hallux (HROML) is important about it can affect the back biomechanical . The aim of this research is to investigate if the HROML may appear as a risk factor of CLBP~HROML affect the foot position, and consecuently may induce to alter as compensatory mechanism the normal biomechanical of the leg, hip and back.

Foot disorders have been recognized as being linked to chronic low back pain

216 eligible adolescents, along with one accompanying parent, will complete a Qualtrics baseline battery via a secure video-conference platform. This battery will be followed by a 3-week (ESM) period. In preparation for this 3-week period, adolescents with a personal smartphone will be assisted in downloading the ecological sampling method (ESM) app during the initial lab session. The participants will then receive an ESM tutorial, and a research team member will review each survey question with the adolescent to ensure comprehension. At the end of the initial session, participating families will schedule a second, brief meeting with the lab to help the adolescent set up the online intervention, which will be completed after the ESM period.~During the ESM period following the baseline battery, adolescents will be prompted to complete the same 2-minute, 8-item survey 5 times per day for 21 days, via a smartphone-based, encrypted data collection app (LifeData). Notifications to complete surveys will occur every 2-3 hours. Responses will be deemed valid if completed within 2 hour of notification, ensuring at least 1-hour lags between surveys.~Once the 3-week ESM period is complete, adolescents will be randomly assigned to receive 1 of 3 web-based single session interventions (SSIs) at a second secure video conference session. The second video conference session will be brief and is meant to help adolescents access the online intervention, which they will complete by themselves. This second session will take place within 2-3 weeks after the ESM period. Immediately pre- and post-SSI, adolescents will complete a limited number of self-report questionnaires by themselves to index shifts in proximal outcomes.~The adolescent and parent pairs will, on their own, complete follow-up assessments at post-intervention. These assessments are abridged versions of the baseline battery. To enable longitudinal analysis of outcome trajectories, adolescents and parents will complete online follow-up questionnaires (including subjective reports of clinical and functional outcomes) 3, 6, 12, 18, and 24 months post-intervention. All follow-up surveys will be completed via Qualtrics, through personalized links sent to the family.~All families will be debriefed by email, and the intervention SSI condition assignment will be revealed, after 24-month follow-up is complete. At this time, adolescents will be offered the opportunity to remotely complete the SSIs they did not originally receive.

We will recruit 216 subjects meeting the eligibility criteria. After completing a baseline battery session via secure video conferencing and 3-week phone survey period, adolescents will be randomly assigned to receive 1 of 3 web-based single session interventions (SSIs) at a second secure video conference session. This second session for the intervention will take place within 2-3 weeks after the phone survey period. Immediately pre- and post-SSI, adolescents will complete a limited number of self-report questionnaires to index shifts in proximal outcomes. Participants, both adult and youth, will complete additional follow-up questionnaires 3, 6, 12, 18, and 24 months post-intervention. Participants will complete the intervention, including the pre- and post- SSI questionnaires, and follow-up surveys on their own.

There is growing concern regarding the impact of COVID-19 and social isolation on mental health and wellbeing, particularly adults living with type 2 diabetes (T2DM), who are at greater risk for mental health issues than the general population. Self-management education and support for healthy eating, physical activity, glucose monitoring, medication adherence and problem solving are vital components of diabetes care. Due to social distancing and limited care and resources, that are likely to persist in the post pandemic phase other innovative service models should be developed and adopted to improve service delivery. The overall goal of this research program is to evaluate the effectiveness of a Technology-Enabled Collaborative Care program. In this study, we examine the feasibility of such a program, called the Technology-Enabled Collaborative Care (TECC) for T2DM designed to support patients with diabetes and mental health concerns during COVID-19.

The overall goal of this research program is to evaluate the effectiveness of a Technology-Enabled Collaborative Care program. In this study, we examine the feasibility of such a program, called the Technology-Enabled Collaborative Care (TECC) for type 2 diabetes designed to support patients with diabetes and mental health concerns during COVID-19.

The objective of the study is to identify socio-demographic factors, behaviors and practices associated with infection with SARS-CoV-2 to help determine where and how patients mostly get infected with SARS-CoV-2.~The study will focus on sociodemographic data (age, gender, location of residence, socio-economic level, etc.), behaviors and practices (adherence to hand-washing, mask-wearing, work habits, meetings, etc.), the places they visit (public transportation, bars, restaurants, sport facilities, etc.).~It is a case-control study including :~cases identified by the nationwide system of positive SARS-CoV-2 tests (SIDEP) (currently limited to RT-PCR) and invited to participate by CNAM, which hosts the data from the nationwide test system, through a nationwide email campaign sent once a week; cases will be asked if they can tell where they most probably were infected, leading to a detailed description of the circumstances of the contamination, including whether the suspected contamination took place within the household or not.~controls included via Ipsos, a polling institute with access to personal data from a panel from which they will include controls matched on age (divided into 10-year categories up to 68 years old included as expected adherence to an online questionnaire quickly drops beyond that age), gender and geographic area (departement); invitations will be sent every week via email to adapt the profile of recruited controls to the age, gender and geographic profiles of the cases that participated in the previous week;~cases will be offered to invite a person they live with to participate in the study offering another case-control analysis inside a household. Cases will be recommended not to invite the person that they suspect was responsible for their contamination, if a intra-household contamination is suspected. They will indicate the email address of that person to allow sending of an invitation via email. These participants will be required to report the result of the test as recommended by contact tracing guidelines to determine whether they are cases or controls.~Analysis will also include descriptive analysis:~Estimation of the proportion of cases infected within the household or outside~Among the cases with a extra-household contamination suspicion, proportion of cases for whom infection circumstances are known and description of these circumstances~Proportion of cases for whom no specific circumstance of contamination could be evidenced.~Questionnaires will focus on the 10 days preceding :~symptom onset (symptomatic cases)~day of testing (asymptomatic cases)~day of symptom onset of the first case within a household (people from the same household as cases) or testing of the first case if they are asymptomatic~questionnaire completion (Ipsos-recruited controls)~Participants will be offered at the end of the online self-administered questionnaire to indicate a phone number. Among those agreeing to do so, a random sample of case-control pairs and cases of particular interest (eg with specific contamination circumstances) will be called within two weeks following the online questionnaire for a more detailed telephone questionnaire to measure reliability of online retrieved data and explore more specific aspects of SARS-CoV-2 transmission.

The objective of the study is to identify socio-demographic factors, behaviors and practices associated with infection with SARS-CoV-2 to help determine where and how patients mostly get infected with SARS-CoV-2.~It is a case-control study including :~cases identified by the nationwide system of positive SARS-CoV-2 tests (COVID-19 diagnosis information system, SIDEP) (currently limited to qRT-PCR) and invited to participate by the National Health Insurance (CNAM) which hosts the data from the nationwide test system;~controls included via Ipsos, a polling institute with access to personal data from a panel from which they will include controls matched on age (divided into 10-year categories), gender and geographic area (departement);~cases will be offered to invite a person they live with to participate in the study offering another case-control analysis inside a household. These participants will be required to report the result of the test as recommended by contact tracing guidelines to determine whether they are cases or controls.~Data will be collected via a self-administered online questionnaire. Some of the participants will be called for a complementary telephone questionnaire to measure reliability of online retrieved data and explore more specific aspects of SARS-CoV-2 transmission.

This is a multicenter study and will enroll approximately 542 participants.~The total duration of study participation for each participant will be 56 weeks, with up to 4 weeks for screening, and for 52 weeks after the first administration of either ABP 654 or ustekinumab.~After confirmation of eligibility, all participants will be randomized in a 1:1 ratio into 2 treatment groups (Group A will receive ABP 654, and Group B will receive ustekinumab) stratified by prior biologic use for psoriasis (yes versus [vs] no), geographic region, and baseline body weight (BW).~Based on the psoriasis area and severity index (PASI) score (to determine better improvement or partial improvement) at week 28, the participants in the study will proceed as follows:~Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered to have completed the study and will complete end of study procedures (ie, week 52 procedures), and those unable to complete week 28 visit, or did not have a PASI assessment completed, will be discontinued from the study.~Participants who achieve PASI 75 response or better improvement will continue on the study and will be re-randomized in a blinded fashion such that participants initially randomized to Group A (ABP 654) will continue to receive ABP 654 and those in Group B (ustekinumab) will re-randomized, to either continue on ustekinumab (Treatment Group B1) or switch to ABP 654 (Treatment Group B2).~Participants with PASI 50 response or better but less than PASI 75 response and on the Investigator's decision, participants will continue on the originally assigned treatment with dose intensification and will not be re-randomized. However, participants that do not dose intensify will be re-randomized.

The purpose of the study is to evaluate the efficacy, safety, and immunogenicity of ABP 654 compared with ustekinumab in participants with moderate to severe plaque psoriasis.

STOP PEDS is a pilot study of children with CF ages 6-18 across 10 sites in North America. The primary goal is to assess the acceptability and feasibility of a multicenter randomized trial comparing immediate antibiotics versus tailored therapy for pulmonary exacerbation (PEx) treatment in this population. The primary endpoint is the proportion of participants in the tailored arm who did not take any oral antibiotics in the 28 days following randomization.~Ultimately, we want to learn:~What is the best way to treat pulmonary exacerbations?~Should everyone with a pulmonary exacerbation take antibiotics?~Do the benefits of starting antibiotics at the first signs of illness outweigh the possible risks, like side effects and antibiotic resistance?~This pilot study is designed to determine if an interventional study to help answer these questions is feasible. Up to 120 participants will be enrolled and followed through their well state of health, then for 28 days following their first randomized exacerbation. Enrollment will stop after 80 pulmonary exacerbation events have been randomized, even if this does not require 120 participants. Due to the nature of the study, the identity of treatment assignment will be known to investigators, research staff, and patients (ie, not blinded).~Total duration of this pilot study is expected to be approximately 18 months: 6 months for participant recruitment and 12 months for follow up. Participants could be monitored for up to 18 months if they do not have an exacerbation. However, it is anticipated that the majority of participants will experience a randomizable PEx event and therefore have a shorter follow up period.

STOP PEDS is a pilot study of children with CF ages 6-18 across 10 sites in North America. The primary goal is to assess the acceptability and feasibility of a multicenter randomized trial comparing immediate antibiotics versus tailored therapy for pulmonary exacerbation (PEx) treatment in this population.

In this single-blind randomized controlled trial, 60 eligible adolescents with TID were selected based on a convenient sampling method. Next, the participants were randomly allocated into two parallel groups: intervention (training with digital storytelling method, n=30) or control (training with conventional) n=30) groups. Before and three months after the intervention the patients' levels of self-management behaviors according to Self-Management of TID amongst adolescents (SMOD-A); in addition to the Glycated Hemoglobin test (HbA1c) were measured.

The aim of this study was to evaluate the effects of digital storytelling on the Self-Management behavior of adolescents with type 1 diabetes (TID).

This research study examines the effects of changes in weight, metabolism of glucose and cholesterol in the blood through diet and behavior modification. The main objective of this study was to compare the effects of low carbohydrate intake and consumption of 3 eggs per day, and low energy diet on diabetes control and biomarkers of CVD in obese people. In addition, HDL quantity and size as well as HDL function was compared between the group who ate the whole egg and the group who did not eat the yolk.

This research compare the effects of low carbohydrate intake and consumption of 3 eggs per day, and low energy diet on diabetes control and biomarkers of CVD in obese people.

Obstructive sleep apnea (OSA) is a common sleep disturbance that can cause intermittent hypoxia, hypercapnia, and sleep structure disorders; the latter include prolonged sleep latency, shortened sleep duration, frequent wake-up, and disordered circadian rhythm. During the postoperative period, surgical stress, pain and the residual effects of sedatives/analgesics can aggravate the sleep disorder and physiological changes in OSA patients. The resulting consequence is increased incidence of postoperative complications.~High-flow nasal cannula (HFNC) therapy can improve the oxygenation of OSA patients by forming a certain positive pressure in the nasopharyngeal cavity. Previous studies showed that HFNC therapy can reduce respiratory events, improve oxygenation in patients with moderate to severe OSA.~Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, analgesic and anti-anxiety properties. Unlike other sedative agents, dexmedetomidine exerts its sedative effects through an endogenous sleep-promoting pathway, producing a state like non-rapid eye movement sleep without disturbing respiration. Our previous studies shows that dexmedetomidine supplemented analgesia can improve sleep quality and pain relief in patients after surgery.~The investigators hypothesize that, for patients at high-risk of OSA who are recovering from major non-cardiac surgery and receiving HFNC therapy, dexmedetomidine supplemented analgesia can improve sleep quality and postoperative recovery. The purpose of this pilot randomized controlled trial is to investigate the impact of dexmedetomidine supplemented analgesia on the sleep quality in high-risk OSA patients after major non-cardiac surgery.

Obstructive sleep apnea (OSA) is a common sleep disturbance that can cause intermittent hypoxia, hypercapnia, and sleep structure disorders. The presence of OSA is associated with worse outcomes after surgery including increased incidence of complications. High-flow nasal cannula (HFNC) therapy can improve oxygenation of OSA patients by maintaining a certain positive pressure in the nasopharyngeal cavity. Previous studies showed that, dexmedetomidine supplemented analgesia can improve sleep quality and pain relief. The investigators hypothesize that, for high-risk OSA patients following major non-cardiac surgery with HFNC therapy, dexmedetomidine supplemented analgesia can improve sleep quality. The purpose of this pilot randomized controlled trial is to investigate the impact of dexmedetomidine supplemented analgesia on sleep quality in high-risk OSA patients after major non-cardiac surgery.

While ABCB1 (P-glycoprotein 1) upregulation after paclitaxel administration is well known, there is currently no clinically available method for preventing or overcoming it. To develop a therapy able to prevent ABCB1 upregulation and paclitaxel resistance, several ABCB1 inhibitors have been evaluated in combination with paclitaxel in preclinical model systems. Pulsed-dose lapatinib and paclitaxel are synergistic and inhibition of ABCB1 by lapatinib increases sensitivity to paclitaxel. Lapatinib is FDA approved, orally available, and previously studied in combination with weekly paclitaxel for breast cancer at doses of 1000mg to 1250mg daily (7000-8250mg per week). This trial will use twice-daily dosing of lapatinib at a starting dose of 750 mg for 2 days (1500mg a day and 3000mg weekly dose), which is less than half of the continuous dose and has been shown to achieve plasma concentrations at 48 hours that are associated with synergy. Therefore, these findings can be translated into a novel, well-tolerated, and convenient combination regimen with significant potential for clinical activity. This trial will be a phase I dose-escalation study of lapatinib and paclitaxel for platinum-resistant ovarian cancer, which will establish the phase II dose for subsequent efficacy trials.

This trial will be a phase I dose-escalation study of lapatinib and paclitaxel for platinum-resistant ovarian cancer, which will establish the phase II dose for subsequent efficacy trials.

This is a randomized, multicenter, double-blind, vehicle-controlled, 2 arm study to evaluate the safety and efficacy of FMX103 topical foam containing 1.5% minocycline compared to vehicle, in the treatment of participants with moderate-to-severe facial papulopustular rosacea. Qualified participants will be randomized in a 2:1 ratio (active:vehicle) to receive 1 of the following 2 treatments:~FMX103 minocycline foam 1.5%~Vehicle foam~Participants will be assigned to 1 of 2 treatments according to the randomization schedule. Participants will apply (or have applied) the study drug topically once daily for 12 weeks as directed. Participants will be advised to use the study drug at approximately the same time each day. Both the Investigator and participant will be blinded to the study drug identity. Participants will return for visits at Weeks 1, 4, 6, 8, 10, and 12. Efficacy evaluations (inflammatory lesion counts and Investigator's Global Assessment [IGA] score) will be performed at Weeks 4, 8, and 12 during the study.~Note: Originally the two studies FX2016-11 and FX2016-12 were combinedly presented in the protocol registration form under one NCT number (NCT03142451), and later separated since results were analyzed separately.

The primary objectives of this study are to determine the efficacy and safety of FMX103 1.5% minocycline foam applied topically once daily for 12 weeks in the treatment of rosacea.

Patients with Parkinson's disease often show gait impairment and reduced mobility over the disease course. Rare atypical forms of parkinsonism, like multiple system atrophy (MSA) or progressive supranuclear gaze palsy (PSP) develop these features in early disease stages. The reduced mobility and increased time spent in sitting or lying posture leads to loss of physical independence and increased mortality. Since MSA and PSP can currently only be treated symptomatically, a long lasting independence and mobility is therefore of great importance.~A positive effect has already been shown in a few studies on specific physiotherapy in patients with idiopathic Parkinson's disease (IPD), and some small studies also give us an evidence that physiotherapy in atypical parkinsonism can improve mobility.~The Mobility_APP study examines the effect of two types of physiotherapy in patients with MSA, PSP and IPD. The participants are initially assigned to a type of therapy and they learn specific exercises with a physiotherapist every day for two weeks. These exercises will then be continued independently at home for another five weeks. Regular checks in the study center ensure a precise examination of the physical condition, quality of life and gait pattern. The latter will be objectively analyzed with the help of sensors that are worn on the participant's shoes. In addition, before the start and at the end of the study, the participants are also monitored for one week at home using shoe sensors in order to reflect the natural conditions of the patients.~During the entire study, neither the participant nor the study investigator knows what type of therapy is being used in order to guarantee an unbiased analysis (double blinding).~The aim of this double-blind, randomized-controlled study is to determine effective physiotherapy in patients with atypical parkinsonian syndromes in order to maintain mobility for as long as possible. If the exercises learned during physiotherapy can be continued regularly at home and can improve mobility, this means a big step towards autonomous therapy. Frequent visits to therapists can be reduced and sufficient and effective independent therapy can still be carried out during times of crisis or phases with increased motor impairment.~The project is kindly supported by the Fund for the Promotion of Scientific Research (FWF). Together with the German Research Foundation (DFG) and Swiss National Science Foundation (SNF) in Switzerland this project can be carried out internationally in cooperation with renowned centers for neurological and sensor-based research.

Patients with atypical parkinsonism often show gait and mobility impairment manifesting in early disease stages.~In order to maintain mobility and physical autonomy as long as possible for these patients, we will examine the effect of two types of physiotherapy in patients with multiple system atrophy (MSA), progressive supranuclear gaze palsy (PSP) and idiopathic Parkinson's disease (IPD).~The study is divided into an ambulant daily in-patient physiotherapy phase, followed by a home-based training phase. At the beginning and the end of the study, the patients daily activity will be recorded for one week using Physical Activity Monitoring (PAM) sensors.~The aim of this double-blind, randomized-controlled study is to determine effective physiotherapy in patients with atypical parkinsonian syndromes in order to maintain mobility for as long as possible.

A prospective, randomized, single-center study is planned to identify the most effective drug regimen in order to prevent the development of acute pancreatitis after transpapillary interventions of the bile ducts.

The aim of the study is to develop a method for the prevention of acute pancreatitis after minimally invasive interventions of the bile ducts using a drug regimen.

According to statistics, more than half of patients who have undergone cardiopulmonary resuscitation (CPR) die from acute cardiovascular or cerebral insufficiency caused by global ischemia. The survival rate after cardiac arrest and successful CPR is about 10%, with good neurological recovery from 0.9% to 7.8%.~The most common cause of cardiac arrest is heart failure, followed by respiratory failure. Despite progress in the provision of specialized medical care, the proportion of patients who underwent post cardiac arrest syndrome (PCAS) and discharged from the hospital remains very low, and neurological and mental disorders persist forever.~The prevalence of nosocomial cardiac arrest in adults varies, with an average of 6 to 9 cases per 1000 hospitalizations. The prevalence of nosocomial cardiac arrest in adults varies, with an average of 6 to 9 cases per 1000 hospitalizations. About half of inpatient cardiac arrests occur in specialized wards, and the remaining half in other locations, such as intensive care units (ICU) and operating rooms. Common causes of cardiac arrest include coronary artery disease, pulmonary embolism, poisoning with cardiotoxic agents (drugs, antidepressants, cardiac glycosides), metabolic disorders (most often hypo- or hyperkalemia), and sepsis.~Modern methods of intensive care of PCAS provide good results, but require significant diagnostic, therapeutic, human and economic resources. The recommendations of the European Resuscitation Council and the European Intensive Care Society on post-resuscitation care have had an impact on improving the quality of care. In Russia, such recommendations are not accepted. One of the conditions for the development and implementation of methods aimed at increasing the survival rate of patients with PCAS is the collection of up-to-date information on the prevalence, causes and patterns of the development of the disease.~In recent years In Russia, not a single multicenter study has been published on the statistics of survival after cardiac arrest and the results of intensive care. There is also no single algorithm for the treatment of post cardiac arrest syndrome, with the exception of the organ donation protocol; meanwhile, the majority of patients suffering from severe multiple organ failure in the postresuscitation period cannot be donors and die as a result of the progression of multiple organ failure.~Targeted therapy for PCAS includes respiratory and hemodynamic support, temperature management, laboratory monitoring, and anticonvulsant therapy. Predicting the degree of neurocognitive dysfunction remains a clinically difficult issue.~The study of PCAS is undoubtedly relevant and can help identify a number of additional prognostic factors affecting the outcome of the disease.~The purpose of this study is to examine the prevalence of PCAS in Russia, to analyze the effectiveness of intensive care methods, to evaluate the factors associated with death and the development of severe neurological deficits. Research centers are located on the intensive care units. A multicenter retrospective registry cohort study is planned.~The research centers are located on the basis of the ICU, of the Irkutsk Regional Clinical Hospital, Irkutsk City Clinical Hospital No.1, City Clinical Hospital No.3, Irkutsk; Federal research and clinical center of intensive care medicine and rehabilitology, Moscow; Orenburg regional clinical hospital, Orenburg City N.I. Pirogov Clinical Hospital, Orenburg; Kuzbass Clinical Emergency Hospital named after M.A. Podgorbunsky, Kemerovo; Regional clinical hospital, Krasnoyarsk interdistrict clinical hospital of emergency medical care named after NS Karpovich, Krasnoyarsk interdistrict clinical hospital №20 named after I.S. Berzona, Krasnoyarsk interdistrict clinical hospital №4, Krasnoyarsk.~Against the background of the assessment of vital functions, methods of respiratory support, laboratory data, and drug therapy will be compared. Continuous data will be presented as the median and interquartile range for the nonparametric distribution and as the mean and standard deviation for the parametric distribution. The categorical variables will be presented as the number of patients and the percentage of the total number of patients. For record keeping, an individual registration card.

The purpose of this study is to study the prevalence of post cardiac arrest syndrome (PCAS) among ICU patients, to analyze the effectiveness of intensive care, to assess the factors associated with death and the development of severe neurological deficits.

Periprosthetic infection following shoulder arthroplasty is a devastating complication. Infected shoulder arthroplasty not only causes an unexpected health hazard to patients but also imposes a heavy financial burden at both individual and societal levels. The rates of periprosthetic shoulder infection (PSI) have been reported to be 0.80% to 1.46%, but the number of infections is likely to increase as shoulder arthroplasty becomes more commonplace in an aging active population. Diagnosing and treating PSI poses a significant challenge. Unlike periprosthetic infection in other joints, PSI lacks the typical clinical signs and laboratory findings of infection due to the indolent nature of the offending pathogens. At the forefront of this issue is Cutibacterium acnes. Although the typical Staphylococcus, Streptococcus, and Corynebacterium species that reside on the skin surface are the primary targets of most surgical infection prophylaxis regimens, C acnes has emerged as a problematic bacterium because the current prophylactic regimens are insufficient to eradicate C acnes from the surgical field.~C acnes is one of the most common pathogens of infections after shoulder surgery. It is a commensal, gram-positive anaerobic bacillus that resides in the sebaceous glands associated with hair follicles. The colonization with C acnes of the front and back side of the shoulder epidermis is greater than that of other regions of the body because of the high density of the sebaceous glands in that area. C acnes can cause low-grade infections after shoulder surgery, and it has been shown that it is the most commonly detected bacterium after revision shoulder arthroplasty surgery. During revision shoulder arthroscopy cases performed for pain, stiffness, or weakness, 30% of patients had positive culture findings, and 80% of those findings were positive for C acnes. It is believed that C acnes infections occur during surgery when the sebaceous glands in the skin are cut and exposed, leading to C acnes contaminating the surgeon's instruments and gloves and, thus, the surgical wound. Recent studies showed that hydrogen peroxide and benzoyl peroxide were more effective than the conventional skin preparation methods in decreasing the C acnes load in the skin, but as high as 17% of the cultures were still positive for C acnes even with these new measures. Thus, despite all the efforts to eradicate C acnes from the shoulder, C acnes remain an elusive pathogen that is potentially contaminating tens of thousands of shoulder arthroplasties each year.~Surgical diathermy (or electrocautery) has been used routinely for tissue dissection and hemostasis during surgical procedures. In the cutting mode, the use of an electrode delivering a pure continuous sinusoidal wave of low voltage produces as high temperatures as 1000℃, which heats cells within the tissue so rapidly that they vaporize, leaving a cavity within the cell matrix. The heat created dissipates as a stream rather than being transmitted into adjacent tissues. This allows tissue cleavage without damage to surrounding areas. The electrode does not need to be in contact with tissue as an arc is formed producing a clean cut. With the coagulation mode on high power, cutting also occurs, but this produces a larger zone of greater thermal damage. Electrocautery can be used for dissecting fascia and muscle layers, as well as achieving hemostasis, and it has become an integral part of modern surgical practice. A number of clinical studies evaluated the safety and efficacy of cutting electrocautery for surgical incisions in general, plastic, otorhinolaryngological, orthopedic, neurosurgical, and gynecologic procedures. Additionally, systematic reviews and meta-analyses were conducted for the same purposes. The majority of these studies showed that using electrocautery to cut the skin provided the benefits of reduced bleeding, a quicker incision, and decreased postoperative pain with no increase of wound complications when compared to scalpel incisions. Given the high temperatures generated at the tip of an electrode of electrocautery, it is reasonable to assume that making a skin incision with electrocautery could potentially destroy exposed colonies of C acnes in hair follicles and sebaceous glands open on the incisional surface of the skin. The purpose of this study is to examine if making skin incisions using electrocautery will result in decreased C acnes contamination during shoulder arthroplasty. To this end, we propose a randomized clinical trial where patients undergoing shoulder arthroplasty are randomized into two groups - Electrocautery incision group (Electro) vs. Scalpel incision group (Scalpel) - and swab cultures are obtained from the skin incision and operating surgeon's gloves and forceps.

Periprosthetic infection following shoulder arthroplasty is a devastating complication. Diagnosing and treating periprosthetic shoulder infection poses a significant challenge. At the forefront of this issue is Cutibacterium acnes because the current prophylactic regimens are insufficient to eradicate C acnes from the surgical field. It is believed that C acnes infections occur during surgery when the sebaceous glands in the skin are cut and exposed, leading to C acnes contaminating the surgeon's instruments and gloves and, thus, the surgical wound. The purpose of this study is to examine if making skin incisions using electrocautery will result in decreased C acnes contamination during shoulder arthroplasty. To this end, we propose a randomized clinical trial where patients undergoing shoulder arthroplasty are randomized into two groups - Electrocautery incision group (Electro) vs. Scalpel incision group (Scalpel) - and swab cultures are obtained from the skin incision and operating surgeon's gloves and forceps

INTRODUCTION Dry eye disease (DED) is one of the most prevalent conditions at an ophthalmology office that may reach 15 to 40% of prevalence in the population. It is didactically classified as two forms that exist as a continuum: aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE). In EDE patients Meibomian Gland Dysfunction (MGD) is the major etiology in which the insufficient meibum secretion can be decreased by cicatricial (trachoma, ocular pemphigoid, erythema multiforme) and non-cicatricial causes (skin disorders such as acne rosacea and atopic dermatitis, blepharitis).~MGD pathophysiology can be explained by hyposecretion or ducts obstruction, resulting in low delivery of phospholipids and cholesterol that grant stability to the tear film. Hyposecretion of the sebaceous glands can result from intrinsic (age, ethnicity, hormonal profile) and extrinsic factors (chronic blepharitis, Demodex folliculorum infestation, contact lens wear, topical drops). Furthermore, the duct obstruction occurs in a consequence to cicatricial rearrangement of the terminal ducts or by non-cicatricial hyperkeratinization of the lid margins, leading to increased duct pressure, dilatation, and disuse atrophy of the glands.~Questionnaires such as Ocular Surface Disease Index (OSDI) and Dry Eye Questionnaire-5 (DEQ-5) that evaluate the grade of severity of DED and assessment of MGD by noninvasive tear breakup time (BUT) evaluation that measures tear film stability and by meibography under infrared light that analyses gland vitality are central when dealing with any EDE patient.~The treatment of MGD can be very challenging in cases where a clinical approach with non-preserved ocular lubricants, lid hygiene, and warm compresses are not sufficient. Oral tetracyclines can be a good alternative in cases of evident lid inflammation to reduce bacterial colonization and inhibit collagenase action although long-term use intolerance limits its use.~Thermodynamic treatment with a device that performs controlled local heating and massage of the ducts showed clinical improvement and symptoms reduction whereas multiple sessions are necessary. Mechanical debridement of gland ducts terminals with scalpel blade also improved ocular symptoms and gland function of patients with EDE with MGD. A combination of intense pulsed light (IPL) therapy and gland expression has been shown to be an effective treatment to MGD with increases in BUT and improvement of ocular symptoms related to DED.~Plasma jet has been successfully used in Dermatology and is an increasingly popular method for smoothing wrinkles, blunt blepharoplasty, as well as performing thermal ablation for superficial skin layers.~The investigators propose a new treatment for refractory MGD patients with plasma jet with a device used in Dermatology to remove the hyperkeratinization layer from the lid margin to unblock terminal gland ducts and use thermal stimulation to enhance meibum delivery.~METHODS A prospective, interventional clinical safety and efficacy trial to determine the efficacy and safety of the treatment of refractory MGD patients with plasma jet will be conducted at Ophthalmology Department at Escola Paulista de Medicina (UNIFESP) with 25 Caucasian patients.~All patients will be instructed about the study design and will be given full access to the results at any time of the protocol. All will sign an informed consent form and have their identity protected in accordance with patient medical confidentiality. This case series is in accordance with Good Clinical Practices and the Declaration of Helsinki.~Patients will be submitted to an ophthalmology workup with best-corrected visual acuity (BCVA) (ETDRS chart), dry eye questionnaires (DEQ-5 and OSDI), corneal topography, bulbar redness, tear meniscus height, noninvasive breakup time (NBUT), tear film osmolarity, meibography under infrared light, meibomian gland expression and Marx line assessment. All exams will be performed before and 30 days after the plasma jet application.~Patients will be instructed about the procedure by the ophthalmologist and a nurse and the procedure will be performed after topical anesthesia with lidocaine 2.0%. The plasma jet will be applied 3 times on both superior and inferior terminal gland ducts in the lid margins with a 14.4mm tip and intensity of 5 on the device (0,9W) reaching only the superficial epidermis. Patients will receive topical antibiotics and corticosteroids after the procedure. During all periods (90 days) patients will use sodium hyaluronate 0,15% and actinoquinol at the recommended dosage of twice a day.~The software program GraphPad Prism version 7.0 will be used to conduct the statistical analyses. Continuous data distribution will be verified by the Kolmogorov-Smirnov normality test. Data will be analyzed by the Kruskal-Wallis test with the Wilcoxon test considering 2-time points for nonparametric variables and paired t-test for parametric variables. All p values of < 0.05 will indicate statistically significant differences.

PURPOSE: The investigators propose a new treatment for refractory Meibomian Gland Dysfunction (MGD) patients with plasma jet to remove the hyperkeratinization layer from the lid margin to unblock terminal gland ducts and use thermal stimulation to enhance meibum delivery.~METHODS: A prospective, interventional clinical safety and efficacy trial with 25 patients from the Department of Ophthalmology at Escola Paulista de Medicina (UNIFESP) to determine the efficacy and safety of the treatment of refractory MGD patients with plasma jet on both upper and lower lids. Patients will be submitted to an ophthalmology workup with best-corrected visual acuity (BCVA) (ETDRS chart) and dry eye questionnaires (DEQ-5 and OSDI). Bulbar redness, tear film meniscus height, noninvasive breakup time (NIKBUT), meibography under infrared light will be measured with Keratograph (Oculus®). Following, tear film osmolarity (i-PenTM), meibomian gland expression, and Marx line assessment. All exams were performed at the baseline, 30 days, and 90 days after the plasma jet application.

This is a Phase 2, multi-center, randomized, parallel, open-label, positive-controlled clinical trial. The objective of this trial is to evaluate the early bactericidal activity, safety and tolerability of WX-081 patients with drug-naive&susceptible and drug-resistant tuberculosis. and the efficacy in participants with drug-resistant tuberculosis.~This trial will be divided into core research stage (stage 1) and extended research stage (stage 2). During stage 1, a panel of 44 participants with drug-naive&susceptible tuberculosis will be randomized to receive either WX-081(including 3 groups:150mg qd, 300mg qd, 450mg qd. n=12 per group) or standard treatment (n=8) for 2 weeks, and then followed by a follow-up period of 2 weeks. A panel of 40 participants with drug-resistant tuberculosis will be randomized to receive either WX-081 (400mg qd, n=20) or bedaquiline (400mg qd, n=20) for 2 weeks. During stage 2, the 40 participants with drug-resistant tuberculosis will receive WX-081(150mg qd) + MBT treatment (ie. multi-drug background treatment) and bedaquiline (200mg tiw) +MBT treatment for 6 weeks respectively, and then followed by a follow-up period of 4 weeks.

This is a multi-center, randomized, parallel, open-label, positive-controlled Phase 2 clinical trial, which aims to evaluate the early bactericidal activity, safety and tolerability of WX-081 in patients with drug-naive&susceptible and drug-resistant tuberculosis. Also the efficacy of WX-081 will be explored in participants with drug-resistant tuberculosis.

PICS describes 'new or worsening impairments in physical, cognitive or mental health status arising after critical illness and persisting beyond acute care hospitalization'. Different critical care professional and scientific societies have identified long-term functional outcomes after critical illness as an important target for research and clinical improvements, and there is general agreement that research on PICS should be a priority for the critical care community.~Post-ICU subjects may experience physical problems, such as muscles weakness and wasting, caused by prolonged bed rest and immobility during the ICU stay and by critical illness polyneuropathy and myopathy developing during the acute illness; organ dysfunction; chronic pain; mental health problems including depression, anxiety or post-traumatic stress disorder (PTSD); and neurocognitive impairments which are predominantly represented by memory dysfunction and executive function impairment. The impact of these problems on the subject's health status is huge, which reduced quality of life, and impaired functional status, and daily functioning.~Many survivors incur substantial healthcare costs, lose employment, and find their social networks wholly changed. The costs to subjects and families are high: ICU survivorship is associated with decreased return to work, and the loss of earnings plagues both patients and caregivers.~Prior studies in which researchers have examined outcomes among ICU survivors have been mainly restricted their assessments to specific patient populations and have used only limited outcome measures or the follow-up period was relatively short-term. Moreover, few studies have explored the association between acute care events and long-term sequelae as well as the underlying pathophysiological mechanisms.~The researchers appertaining to the present study implemented a follow-up clinic to describe the frequency of physical, cognitive, and mental impairments and their evolution over time in subjects surviving critical illness. The researchers also aim at understanding the pathogenetic mechanisms underlying these impairments and their association with acute care events.

Survivors of critical illness may suffer from persistent physical, cognitive and mental impairments, such as muscle weakness, dysfunction in the memory and executive domains, post-traumatic stress disorders, depression, and anxiety. This syndrome is referred to as Post Intensive Care Syndrome (PICS).~This study aims to assess the frequency of impairments, their evolution over time, and to understand the pathogenetic mechanisms and the association between long-term sequelae and acute care events.

The current study is a pragmatic randomized pilot trial examining the feasibility and effects of a brief therapist guided online self-help program based on Cognitive behavioral therapy (CBT) . Participants will be randomized to either a treatment as usual condition (TAU) or to TAU plus CBT.~Participants will be recruited via the Swedish national gambling helpline. After assessment for eligibility participants will be randomized, using block randomization to ensure balanced groups, to either TAU or TAU+CBT.~The participants will be measured; at baseline, weekly during the intervention (6 weeks), immediately after the intervention and at 6 weeks after treatment termination. Informed consent will be collected prior any data collection.

A pragmatic randomized pilot trial primarily examining the feasibility of a brief therapist guided online self-help program based on Cognitive behavioral therapy (CBT). Participants will be randomized to either a treatment as usual condition (TAU) or to TAU plus CBT.

RATIONALE AND RESEARCH QUESTION Distal pancreatectomy (DP) is defined as the resection of the left portion of the pancreas extending from the neck to the tail of the gland. DP is burdened by the occurrence of clinically-relevant postoperative pancreatic fistula (CR-POPF) in a significant proportion of patients.Traditionally, during DP drains were placed intraoperatively in proximity of the pancreatic stump to mitigate the potential occurrence of POPF. Postoperatively, drains were usually kept in place until a POPF was ruled out by the presence of drain fluid amylase (DFA) values lower than 3-fold the upper limit of normal serum amylase, and a non sinister appearance of drain fluid in accordance with the International Study Group on Pancreatic Surgery (ISGPS) definition. For this reason, drains were usually maintained in place after surgery for at least 5 - 7 days. Although there is some preliminary evidence that early drain removal in the subgroup of patients with DFA1 < 2,000 U/L, no prospective study has yet evaluated the impact of an early drain removal strategy compared to standard management. Therefore, the overall aim of this study is to contribute evidence about the effect of an early drain removal policy on postoperative outcomes following distal pancreatectomy.~The primary research question is to evaluate to what extent does early postoperative drain removal according to a validated DFA1 impact on clinically-relevant POPF rate after distal pancreatectomy in comparison to standard drain management. The primary (confirmatory) hypothesis is that, early drain removal will result in a reduced proportion of patients experiencing grade B-C POPF according to ISGPS definition.~Furthermore the exploratory hypotheses that, in comparison to standard care, early drain removal will: (1) reduce time to postoperative functional recovery, (2) reduce number and severity of postoperative complications, (3) reduce postoperative surgical site infections, (4) improve self-reported physical function status, (5) improve generic health-related quality of life and (6) be cost-effective, will be tested.~STUDY DESIGN AND PARTICIPANTS The study is designed as a two-group, assessor-blind, randomized trial. Participants will be randomly assigned with a 1:1 ratio into one of two groups: (1) standard drain management or (2) early drain removal strategy. The intervention will be provided during hospital stay. Adult people with pancreatic body or tail diseases (i.e. pancreatic cancer, cystic neoplasms, pancreatic neuroendocrine tumors, etc.) planned for distal pancreatectomy with or without splenectomy at the San Raffaele Hospital IRCCS (HSR) will be considered for inclusion.~RECRUITMENT PROCESS~The step-by-step recruitment process is described below:~Patients scheduled for elective distal pancreatectomy who meet the inclusion/exclusion criteria will be informed about the study by a surgeon at their first office consultation~If the patient has interest in participating in the study, at the preoperative clinic visit or at the time of hospital admission, a trial investigator will discuss the study in detail with the patient~The potential participant or their legal representative will read the consent form. Once the informed consent is signed and the patient enrolled in the study, preoperative assessment will be undertaken~SURGICAL TECHNIQUE The standard surgical procedure for DP will be performed and will not be influenced by this study protocol. The choice of minimally invasive versus open technique will be at surgeon's discretion. As a general rule, patients with benign lesions or neuroendocrine tumors will be approached laparoscopically, while pancreatic cancer cases are discussed on an individual basis according to tumor location and vessel proximity. Splenectomy and standard lymphadenectomy will be routinely performed in cancer patients. A spleen preserving procedure with preservation of splenic vessels will be attempted only in non-neoplastic cases at surgeon's discretion. Pancreatic stump transection will be performed with a stapler in laparoscopic procedures, whereas in open procedures the pancreas will be cut using the scalpel followed by selective suturing of the pancreatic duct when visible.~To evaluate the association between pancreatic parenchymal structure and occurrence of POPF, in addition to standard pathology assessment, the pancreatic specimen will undergo a specific pathological evaluation. Haematoxylin and eosin (H&E) stained sections (between 1 and 4 for each case) of the pancreatic resection margin will be reviewed by two expert pancreatic pathologists, blinded to all clinical information. All the definitive slides will be assessed for their acinar, fat and fibrosis content as a proportion of the total surface area. Acinar, fat and fibrosis scores will then calculated for each patient so that their sum is equal to was 100%. The final score for each patient will be the result of two pathologists reached a consensus agreement by the two pathologists.on the scoring of each patient.~DRAIN MANAGEMENT~At the end of the operation, after reassessing exclusion criteria, participants will be randomized into one of two groups:~Standard postoperative drain management: Participants randomized to this group will receive the current standard of care at our institution. The drain will be maintained at least until postoperative day 5. If DFA on POD 5 is lower than 3-fold the upper limit of normal serum amylase value, and/or the drain fluid does not appear sinister (i.e. varying from dark brown to greenish fluid to milky water to clear spring water pancreatic juice like appearance) according to the clinical team, the drain will be removed. If the drain is maintained in place beyond POD 5, it will be removed inhospital or after discharge when the daily amount is lower than 10 ml and there are no signs of ongoing infection.~Early drain removal: Participants randomized to this group, will have an early drain removal (before POD 3) if DFA on POD1 is lower than 2000 U/L and/or the drain fluid does not appear sinister (i.e. varying from dark brown to greenish fluid to milky water to clear spring water pancreatic juice like appearance) according to the clinical team. If DFA is greater than 2000 U/L, the drain will be maintained in place. If the sample on POD1 DFA is not available (e.g. drainage fluid is viscous and amylase value cannot be evaluated) or the sample could not be analyzed (e.g. the fluid collection tube is lost or not sealed) DFA will be evaluated on POD2, and drain removal will be considered if DFA is lower than 2000 U/L. If DFA on POD 3 is lower than 300 U/L, that is 3-fold the upper limit of normal serum amylase value, and/or the drain fluid does not appear sinister (i.e. varying from dark brown to greenish fluid to milky water to clear spring water pancreatic juice like appearance) according to the clinical team, the drain will be removed. Otherwise, the drain will be kept in place and .the patient will then follow standard postoperative drain management as described above.~All patients will measure serum amylase and drain fluid amylase along with other routine postoperative laboratory tests on POD 1 - 3 - 5 as the current standard of care.~Furthermore, as drain fluid microbial contamination is considered to play a potential role for the POPF occurrence, a drain fluid culture for aerobic and /anaerobic microorganisms will be performed on POD1 (baseline) and POD5, in order to evaluate the predictive ability of early bacterial contamination in the abdominal fluid for clinically relevant POPF.~MEASUREMENTS AND OUTCOMES Demographic data, medical history, laboratory values and information relevant to the surgical procedure will be recorded. The main (confirmatory) outcome of interest will be the occurrence of CF-POPF at 90 days after surgery, defined as grade B or C POPF according to the 2016 ISGPS definition.~The proportion of patients discharged home without an abdominal drain represents the explanatory outcome measure. It will be evaluated at time of hospital discharge.~Time to functional recovery (TFR) will be measured by subtracting the date of surgery from the date when participants achieves standardized criteria (tolerance of oral intake, recovery of lower gastrointestinal function, adequate pain control on oral analgesia, ability to mobilize and self-care and no evidence of untreated medical problems).~Postoperative complications occurring during the index admission or in a subsequent readmission, when related to surgery, will be recorded up to 90 days after surgery and graded by severity using the Dindo-Clavien classification. Additionally, the Comprehensive Complication Index will be calculated.~Postoperative morbidity at 90 days after surgery will include:~Surgical site infections classified as superficial incisional, deep incisional or organ-space according to the definition by the Center for Disease Control and Prevention~Post-pancreatectomy hemorrhage and delayed gastric empting as defined by the ISGPS Self-reported activity status will be measured using the Duke Activity Status Index (DASI) and Generic heath related quality of life will be measured using the Patient Reported Outcome Measure Information System (PROMIS)-29+2 Profile v2.1. These questionnaires will be completed before surgery, at 15, 30 and 90 days after surgery. Cost-effectiveness will be estimated by the ratio of differences in costs to differences in quality-adjusted life years (QALYs) between the two groups.~BLINDED ASSESSMENT An examiner blinded to the participants' treatment allocation will obtain all measures. The code for group allocation will not be revealed until all analyses are completed. The effectiveness of blinding will be estimated by asking the assessor to guess the participant's group allocation at the completion of the 90 days assessment. It is not possible to blind the participants to their group assignment.~STATISTICAL CONSIDERATIONS AND TIMELINES Recent studies carried at the HRS Division of Pancreatic Surgery showed that, when standard drain management is used, the proportion of patients developing CR-POPF is approximately 46%. Sample size requirement for the present study was estimated for an α level of 0.05 and 80% power to detect a 23% reduction in this proportion (risk ratio 0.23/0.46=0.5). According to this estimate, a sample of 66 participants per group is considered sufficient for our analysis. A sample size of 75 participants per group (total sample of 150) is targeted to account for possible dropouts. Regression models will be used to test the main hypothesis related to the superiority of early drain removal based on a reduction of CR-POPF at 90-days after surgery. The randomization list will be created with the Block randomization rule, in order to reduce bias and achieve balance in the allocation of participants to the two arms.~The Division of Pancreatic Surgery at HSR performs about 90 distal pancreatectomies annually. Based on previous trial experience, approximately 90% of these patients will be eligible and agree to participate. Therefore, 150 participants could be feasibly enrolled in 21 months. With an additional 90 days follow-up required for the primary outcome, the timeline for this study is 24 months.~SAFETY Previously completed studies have shown that early drain removal in patients with DFA1 values lower than a validated threshold in patients undergoing pancreatic head resection is not only safe but beneficial, as it reduces the incidence of CR-POPF and the risk of further complications due to the persistence of a foreign body

Main indications for distal pancreatectomy (DP) are pancreatic body and tail tumors including ductal adenocarcinoma, neuroendocrine tumors, and cystic neoplasms. Despite a less invasive operation with lower morbidity compared to pancreatic head surgery, DP is burdened by the occurrence of clinically-relevant postoperative pancreatic fistula (CR-POPF) in a significant proportion of patients.~Drain fluid amylase (DFA) on POD 1 (postoperative day 1) > 2,000 U/L appears as the best performing threshold to predict the occurrence of CR-POPF after distal pancreatectomy. Although there is preliminary evidence that early drain removal in the subgroup of patients with DFA1 < 2,000 U/L may reduce POPF, no prospective study has yet evaluated the impact of an early drain removal strategy compared to standard management.~The research question of this study is to evaluate to what extent early postoperative drain removal according to a validated DFA1 impact on clinically-relevant POPF rate after distal pancreatectomy in comparison to standard drain management. The primary hypothesis is that, early drain removal will result in a reduced proportion of patients experiencing grade B-C POPF according to ISGPS definition.~The proposed study is a two-group, assessor-blind, randomized trial. Participants will be randomly assigned with a 1:1 ratio into one of two groups: (1) standard drain management or (2) early drain removal strategy.~In this study adults (>18 years) patients with pancreatic body or tail diseases planned for distal pancreatectomy with or without splenectomy will be enrolled.The primary outcome is the POPF at 90 days after surgery, defined as grade B or C POPF according to ISGPS definition.~Participants will be asked to complete some questionnaires in order to assess their general health status, and they will be evaluated at time of hospital admission, at 15 days, at 30 days after surgery (via telephone follow-up), and at 90 days after surgery (via telephone follow-up).

The aim of the study is to evaluate the effect of a person-centred nurse-led outpatient clinic on health related quality of life, for persons with AF. Secondary outcomes are effects on anxiety, depression, illness perception, symtom burden, life style and health economics.~We plan a randomized controlled trial comparing person centred nurse led care vs. standard care. A sample size of 100 persons per group will be recruited.~Data will be collected through questionnaires, medical records, interviews.

The aim of the study is to evaluate the effect of a person-centred nurse-led outpatient clinic on health related quality of life, for persons with AF. Secondary outcomes are effects on anxiety, depression, illness perception, symtom burden, life style and health economics.

This is a phase Ib, dual-center, open-label, single-arm, clinical study to determine the safety, tolerability and trends of efficacy of ALECSAT as an add-on therapy to standard treatment with carboplatin and gemcitabine in female patients with locally advanced inoperable or metastatic TNBC, which has received no more than two prior systemic therapies for mTNBC.~Study treatments will continue until any of the following occurs: disease progression is locally verified using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); unacceptable toxicity; intercurrent illness that necessitates discontinuation of study treatment; Investigator's decision to withdraw the patient; pregnancy; patient noncompliance with study treatment or procedure requirements; withdrawal of consent to treatment; death; end-of-treatment visit at month 18; or other administrative reasons requiring cessation of study treatment. If chemotherapy is discontinued during the study, the patient will be allowed to continue in the study on ALECSAT treatment after discontinuation of chemotherapy, based on the Investigator's judgement. In addition, if clinical assessments indicate an anti-cancer effect of ALECSAT treatment (at the discretion of the investigator) at end of study, patients will be offered to continue ALECSAT treatment after end of the study under approved named patient use. Response assessment according to RECIST v1.1 will be performed at weeks 9 (±7 days), 18 (±7 days), and 27 (±7 days) after treatment start as by local hospital standards. Imaging will continue every 9 weeks (±7 days) thereafter during the first year, independent of any treatment delays. Response assessment will be performed every 12 weeks (±7 days) after the first year. Safety will be monitored according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (v5.0). Patients who discontinue study treatments for reasons other than PD will continue post-treatment imaging studies for disease status follow-up as per protocol, i.e., every 9 weeks (± 7 days) and 12 weeks (± 7 days) during the first year or second year of study participation, until disease progression, start of a non-study anticancer treatment, withdrawal of consent to study participation, death, or end-of-treatment visit 18 months.

A phase Ib study to investigate the safety, tolerability and trends of efficacy of ALECSAT treatment as an add-on therapy to carboplatin and gemcitabine in patients with locally advanced or metastatic triple-negative breast cancer.

This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 72 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.

A study of CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

This study is an investigation of a new delivery system of the Patient Health Questionnaire - 9 (PHQ-9), a clinically accepted tool for diagnosing major depressive disorder. The purpose of the study is to examine if the new delivery system of the PHQ-9 is effective at capturing participant depression levels. The new version uses a Mirror device, which is similar to a smart television with a mirror interface. The device records auditory responses to the PHQ-9 through Amazon Alexa. We will be comparing the responses from the Mirror device to those given on the clinically established paper format. If proven effective at capturing depression levels of patients, future studies may investigate if the new format can be used to improve at home clinical care.

This study investigates a new delivery method for the Patient Health Questionnaire - 9 (PHQ-9), a clinically accepted tool for diagnosing major depressive disorder. The new tool records auditory responses to the assesment and the study will examine if the instrument is effective at capturing participant depression levels. If proven effective, future studies may investigate if the new format can be used to improve at home clinical care.

In many developing countries, pediatric cardiac programs are not fully established, and nutrition support algorithm is lack. Therefore, this study aimed to evaluate the the efficacy and safety of the implementation of an algorithm for enteral nutrition support compared with usual standard practice in children with malnutrition status with congenital heart disease. The usual standard practice for feeding often interrupted by retention in the gut and then choose the parenteral nutrition support especially in the patients with unstable hemodynamic status. Actually tiny and continuous feeding would improve the gut function and reach the adequate energy supply.

The purpose of this trial is to evaluate the efficacy and safety of the implementation of an algorithm for enteral nutrition support compared with usual standard practice in children with malnutrition status with congenital heart disease

placenta accreta spectrum is group of disorders which have a depate about the best way of management. this is a descriptive study about the best techniques to reduce morbidity and mortalities related to it.~surgical management of placenta accreta~short term follow up to the outcomes~long term follow up

placenta accreta spectrum is group of disorders which have a depate about the best way of management. this is a descriptive study about the best techniques to reduce morbidity and mortalities related to it.

SNX281 is a small molecule activator of the Stimulator of Interferon Genes (STING) protein, with good drug-like properties. Activation of STING initiates the innate immune response and enhances the adaptive immune response, which could potentially activate immune responses to tumors and enhance the response to certain immunotherapies.~This study is a phase I, first in human, open-label study of SNX281 conducted in subjects with advanced solid tumors and lymphomas. The study will comprise of two treatment arms: one evaluating SNX281 as a single-agent, and the other evaluating SNX281 in combination with pembrolizumab. Each treatment arm is designed to include a dose escalation phase followed by a dose expansion phase intended to establish the recommended Phase 2 dose (RP2D).~In the dose escalation phase of each treatment arm, successive cohorts of participants will receive increasing doses of SNX281 designed to determine the maximum tolerated dose (MTD), the dose with maximum pharmacologic activity, or the maximum feasible dose, as a single-agent and in combination with pembrolizumab.~The dose expansion phases of each treatment arm will begin following the determination of an MTD or alternative dose of SNX281 in each respective treatment arm. The single-agent treatment arm of SNX281 is planned to evaluate at least 2 expansion cohorts in ovarian cancer and colorectal carcinoma while the combination treatment arm of SNX281 and pembrolizumab is planned to enroll subjects with advanced cancer who have relapsed on or have become refractory to prior immune checkpoint therapy given in an indicated setting.

This clinical trial is evaluating a drug called SNX281 given by itself and in combination with pembrolizumab in participants with advanced solid tumors and lymphoma. The main goals of this study are to:~Find the recommended dose of SNX281 that can be given to participants safely alone and in combination with pembrolizumab.~Learn more about the side effects and safety profile of SNX281 alone and in combination with pembrolizumab~Learn more about pharmacological characteristics of SNX281 alone and in combination with pembrolizumab~Learn more about effectiveness of SNX281 alone and in combination with pembrolizumab

Obstructive Sleep Apnea (OSA) syndrome is a disorder characterized by repetitive episodes of upper airway obstruction that occur during sleep. OSA lead to desaturation and often lead to an arousal.~Associated features include loud snoring and fragmented non-refreshing sleep and have profound impact on quality of life, on safety on the roads and at work, and on the cardiovascular and metabolic systems.~The standard treatment for apnea remains a device consisting of a pump and nasal mask that provide continuous positive airway pressure (CPAP). CPAP acts as a pneumatic splint that elevates and maintains a constant pressure along the upper airway during inspiration and expiration that prevents airway collapse. The major disadvantage of CPAP is the relatively low compliance.~Appscent developed a non-contact effortless bedside solution based on the following: odors modify respiratory patterns during wake . Mildly trigeminal and pure olfactory odorants do not arouse or wake. Odorants transiently presented during sleep induced a respiratory rejection type response, this suggests that manipulating the respiratory system without waking is viable .

Obstructive Sleep Apnea (OSA) syndrome is a disorder characterized by repetitive episodes of upper airway obstruction that occur during sleep.~The standard treatment for apnea remains a device consisting of a pump and nasal mask that provide continuous positive airway pressure (CPAP). The major disadvantage of CPAP is the relatively low compliance.~Appscent developed a non-contact effortless bedside solution based on the following: odors modify respiratory patterns during wake . Mildly trigeminal and pure olfactory odorants do not arouse or wake.

The Asthma Digital Study is a virtual, two-arm, randomized, controlled trial that will investigate the impact of digital tools on asthma symptom control, exacerbation frequency, healthcare utilization, and medical expenditures. Adults with asthma will be randomized to the passive or active arm in a 1:1 ratio.~All participants will be sent two devices, at no cost-an Apple Watch and a Beddit Sleep Monitor. These are publicly available, commercial devices that have not been modified for this study.~The study will be administered largely through a customized version of CareEvolution's MyDataHelps app (the Study App). Access to the Study App will be provided to all participants. It will be used to administer informed consent and electronic patient reported outcome (ePRO) measures, and for other study purposes. Only active arm participants will have access to Study App features designed to support asthma self-management. These features include smart nudges based on device data, symptom and trigger tracking, evidence-based education, summaries of health metrics gathered from the Apple Watch and Beddit Sleep Monitor, in-app medication refill resources, as well as other resources.~The study duration is 2 years. Participants can keep using the Study App and devices after Year 1, though this is not required. Primary analyses will utilize Year 1 data only. During Year 2, data collection will continue where available, though fewer data will be collected because use of digital tools is not required during Year 2, and health coverage changes may cause loss of access to claims data.

The Asthma Digital Study is a virtual, two-arm, randomized, controlled trial that will investigate the impact of digital tools on asthma symptom control, exacerbation frequency, healthcare utilization, and medical expenditures in adults with asthma.

Patient will tension-type headaches will be randomized to receive 2 sessions per week for 6 weeks (up to 8-12 sessions total) of either: 1. thrust Manipulation, electric dry Needling and exercise or 2. non-thrust mobilization, soft-tissue mobilization, exercise and TENS

The purpose of this research is to compare two different approaches for treating patients with tension-type headaches: thrust Manipulation, electric dry Needling and exercise Vs. non-thrust mobilization, soft-tissue mobilization, exercise and TENS. Physical therapists commonly use all of these techniques to treat tension-type headaches. This study is attempting to find out if one treatment strategy is more effective than the other.

Open-label prospective trial to study efficacy, safety and tolerability of intravenous immunoglobulin (IVIG) once monthly for 6 months in children and adolescents with PANS (including the subgroup PANDAS). Number of subjects: 10. Age range: 4-17 years.~Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a recently defined research diagnosis describing an abrupt, dramatic onset of neuropsychiatric symptoms including obsessions/compulsions and/or food restriction in children. Immunologic mechanisms are suspected, but treatment trials are few.~The primary objective of this study is to evaluate the efficacy of intravenous immunoglobulin (IVIG), 2 g/kg given every 4 weeks for 6 months, to patients with post-infectious PANS/PANDAS, in improving neuropsychiatric symptoms and impairment.~The secondary objectives of this study are to evaluate changes from baseline to follow-up at 3 months, 6 months and 12 months in:~Obsessive Compulsive Disorder (OCD) symptoms~adaptive functioning~quality of life~cognitive functioning~for patients with baseline inflammation signs on cerebral Magnetic Resonance Imaging (MRI) to evaluate changes in these measures after IVIG therapy after 6 months.~number of days of work/school/daily activities missed per subject year due to PANS/PANDAS before and after IVIG therapy~parental care load, e.g. need for sick leave, before and after IVIG therapy~Immunoglobulin (IgG, IgM and IgA) levels at baseline, 3 months, 6 months and 12 months~sustainability of any improvement at 12 months after initiation of IVIG measured with the PANS scale, CGI-S and CGI-I~To assess the safety and tolerability of high dose IVIG therapy~Clinical signs and symptoms (nausea, headache, local reactions)~ALAT~Hemoglobin, complete blood count including leucocyte differential~Investigational product: Intravenous immunoglobulin IVIG (Privigen), 2 g/kg BW every 4th week for 6 months (= 6 infusions).

Open-label prospective trial to study efficacy, safety and tolerability of intravenous immunoglobulin (IVIG) once monthly for 6 months in children and adolescents with PANS. Number of subjects: 10. Age range: 4-17 years.~Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a recently defined research diagnosis describing an abrupt, dramatic onset of neuropsychiatric symptoms including obsessions/compulsions and/or food restriction in children. Immunologic mechanisms are suspected, but treatment trials are few.

The Corona Virus Disease 2019 is rapidly spreading throughout the world. Aerosol is a potential transmission route.~The transmission of severe acute respiratory syndrome coronavirus in humans is thought to be via at least 3 sources: 1) inhalation of liquid droplets produced by and/or 2) close contact with infected persons and 3) contact with surfaces contaminated with severe acute respiratory syndrome coronavirus. There are many respiratory diseases spread by the airborne route such as tuberculosis, measles and chickenpox. Several studies suggested that airborne spread may have played an important role in the transmission of that disease. At present, there is little information on the characteristics of airborne severe acute respiratory syndrome coronavirus containing aerosols, their concentration, or their infectivity.~The aim was to determine airborne severe acute respiratory syndrome coronavirus 2 transmission, their infectivity in in different areas such as patient's room and in medical staff area.~Methods~Cross sectional study of samples from environmental of patient´s room, and medical staff area. Samples will be taken of air using microbial air monitoring systems, and from different surfaces of patient's room and medical staff area, such as computers, mouse and personal protective equipment using cotton swabs. Viral RNA will be determined using Real-Time-Polymerase-Chain Reaction. In positive samples infectiveness will be determined by cell culture under biosecurity conditions.~Statistical analysis will be performed to determine prevalence of positive samples and positive cell culture whit STATA version 15.1.~informed consent will be obtained from all participants

There is little information on the characteristics of airborne severe acute respiratory syndrome coronavirus containing aerosols, their concentration, or their infectivity.The aim was to determine airborne severe acute respiratory syndrome coronavirus transmission, their infectivity in different areas such as patient's room and in medical staff área.

We will partner with Dr. Robert Edwards at the Brigham & Women's Pain Institute. Dr. Edward's is an expert in testing central sensitization using quantitative sensory testing (QST).12 QST involves cutaneous (skin) psychophysical (semi-subjective) testing to assess sensory and pain perception pathways.13 QST identifies the intensity of stimuli (touch) is needed to feel something (threshold of detection) and how perception of stimuli changes if it is repeated many times (temporal summation).14 In people with central sensitization, even light intensity of stimulation is perceived as pain and similar intensity stimuli becomes more painful with multiple applications. We hypothesize that people with chronic pain will demonstrate clinically important reductions in the threshold of detection and temporal summation after IVR, which will demonstrate that IVR can affect central sensitization.~We will complete two types of QST testing: Mechanical Pressure Pain Thresholds (MPPTh) to test for threshold of detection, and Mechanical Temporal Summation of Pain (MTSP) to test for temporal summation. In MPPTh we will measure the amount of pressure needed at the shoulder and thumb (body sites that routinely do not have pain in people with low back pain) to elicit a pain report from participants. In MTSP we will apply a train of 10 stimuli (light pinprick) at the rate of 1 per second on the middle finger and have participants rate the painfulness of the first, fifth, and tenth stimulus.~During the study, we will recruit 20 patients with chronic low back pain from Dr. Edwards' study examining sensory and pain perceptions in patients with chronic pain who use opioids. We will complete QST testing and obtain current pain levels. We will complete 20-minutes of IVR, and then complete QST testing again. We will compare pre-IVR MPPTh and MTSP with post IVR levels. We anticipate short term, clinically important decreases in QST levels providing initial confirmation that IVR can positively change central sensitization.

Patients with chronic low back pain from Dr. Robert Edwards' study at the Brigham & Women's Pain Institute that examines sensory and pain perceptions in patients with chronic pain who use opioids will complete quantitative sensory testing (QST) and current pain levels will be obtained. Subsequently, 20-minutes of Immersive Virtual Reality (IVR) will be completed and then QST testing will be completed again post-IVR.

Tumor is one of the malignant diseases that people face. In 2015, the incidence of malignant tumors was about 3.929 million, and the annual growth rate is about 3.9%. Chemotherapy is currently the most commonly used treatment for patients with tumor, but chemotherapy also brings many other problems, such as thrombocytopenia which can leads to increased medical costs, chemotherapy cycles delayed, and chemotherapy doses reduced. Studies have found that the reduction of the chemotherapy dose and the delay of the chemotherapy cycle will affect the survival rate of patients. So it is an important to solve the problem of chemotherapy-induced thrombocytopenia.~Currently, there are some methods to treat thrombocytopenia such as platelet transfusion, rhTPO, rhIL-11 and other methods. However, these methods have some defects, platelets are at risk of ineffective transfusion, rhTPO may produce neutralizing antibodies and rhIL-11 has serious side effects. Therefore, there is an urgent need for safer and faster methods to treat chemotherapy-induced thrombocytopenia. As a new generation of TPO receptor agonist, avatrombopag has the advantages of being taken with food, no hepatotoxicity, good safety, and rapidly increase platelet count. Therefore, avatrombopag has great research value in the treatment of chemotherapy-induced thrombocytopenia.

To observe the clinical efficacy and safety of avatrombopag for chemotherapy-induced thrombocytopenia in patients with malignant tumors.

This is a randomized, double-blind, double dummy, parallel group, multicenter 24 to 52 week variable length study to assess the efficacy and safety of budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler (MDI) relative to budesonide and formoterol fumarate MDI and Symbicort® pressurized MDI in adult and adolescent participants with inadequately controlled asthma. Approximately 2200 participants will be randomized globally.

This is a variable length study to evaluate the efficacy and safety of budesonide/glycopyrronium/formoterol inhaler in adults and adolescents with severe asthma inadequately controlled with standard of care.

A Sleeve Gastrectomy (SG) is on the long term not always successful in every patient because weight regain can occur. An intervention to prevent weight regain in the future is to place a silicone band (non-adjustable) around the sleeve (Banded-Sleeve Gastrectomy: BSG) which increases weight loss and decreases weight regain on the longer term. The question is whether primary application of a banded sleeve gives a greater weight loss and / or prevent weight regain in the future versus a standard sleeve gastrectomy.~Study is a prospective, randomized, multi centre trial.~Study population: patients who qualify for a SG are eligible to participate. The primary SG patients may participate if there is a BMI of 35 kg / m2 with a morbidly obesity-related comorbidity or a BMI of 40kg / m2 or higher.~Intervention: The standard SG is compared with a banded-SG (BSG)

A Sleeve Gastrectomy (SG) is on the long term not always successful in every patient because weight regain can occur. An intervention to prevent weight regain in the future is to place a silicone band (non-adjustable) around the sleeve (Banded-Sleeve Gastrectomy: BSG) which increases weight loss and decreases weight regain on the longer term. The question is whether primary application of a banded sleeve gives a greater weight loss and / or prevent weight regain in the future versus a standard sleeve gastrectomy.

This is a multi-site, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of ZnAg liquid solution in symptomatic participants with acute COVID-19 (PCR documented SARS-CoV-2 infection) that are not hospitalized at the time of enrollment (e.g., present to an emergency room without being admitted to the hospital or diagnosed in an outpatient clinic setting).~Participants must have presented with two or more symptoms of acute COVID-19 (within 96 hours prior to the Baseline visit) self-reported as moderate or severe at the Baseline visit, including fever, myalgia, fatigue, chest tightness, chills, cough, diarrhea, gastrointestinal distress, headache, sore throat, congestion or runny nose, ageusia, anosmia, nausea, tingling or numbness in the extremities, or shortness of breath. SARS-CoV-2 infection must be confirmed by polymerase chain reaction (PCR) testing within 96 hours prior to the Baseline visit.~Participants who meet all inclusion criteria and none of the exclusion criteria and who formally consent to participate will be randomized 1:1:2 to receive ZnAg (low dose) : ZnAg (high dose) placebo in a double-blind fashion in addition to standard supportive care. Within the active treatment arm, participants will be randomized to receive either low or high dose ZnAg.~Active treatment with 60 ml low-dose ZnAg (Zn 6 ug/ml and Ag 10 ug/ml; equivalent to 0.6 mg Ag, 0.36 mg Zn), po q12 hours or;~Active treatment with 60 ml high-dose ZnAg (Zn 12 ug/ml and Ag 20 ug/ml; equivalent to 1.2 mg Ag, 0.72 mg Zn), po q12 hours;~60 ml matching placebo, po q12 hours~Participants who become clinically unstable during the course of the study (e.g., requiring high-flow supplemental oxygen or mechanical ventilatory support) per the judgement of the site investigator will be admitted to a hospital and their clinical status (e.g., vital status, hospitalization status, respiratory status, COVID-19 ordinal scale) will continue to be tracked per protocol.

This is a multi-site, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of ZnAg liquid solution in symptomatic participants with acute COVID-19 that are not hospitalized at the time of enrollment.

Hip arthroscopy (HAS) is a standard procedure with good mid and long-term results. Postoperative pain is a great concern and postoperative pain management of great importance. High demand for opiates and the associated side effects especially nausea limit the postoperative rehabilitation.~Promising results to reduce postoperative pain and nausea have been achieved by perioperative dexamethasone, which has a strong anti-inflammatory effect reducing pain and inflammation as well as a strong anti-emetic effect, especially in total hip replacement.~It is our goal to compare the effect of perioperative intravenous dexamethasone (3x 4mg Amp. Fortecortin =12mg prior to surgery and 3x4mg Amp. Fortecortin = 12mg at 8.00am of the first postoperative day in 250ml saline solution) to a control group (placebo) (1x 250ml saline solution postoperative day 1 at 8.00am) regarding pain level, opiate consumption, postoperative nausea and patient satisfaction.~A double-blinded prospective randomized control trial including 60 patients receiving elective unilateral HAS will be conducted.

The purpose of this study is to assess the effect of Dexamethasone on postoperative pain and nausea after hip arthroscopy.

Fragile X Syndrome (FXS) and Williams-Beuren Syndrome (WBS) are relatively rare disorders characterized by developmental delay associated to socio-communicative deficit and autistic-like behaviours. FXS is one of the most common monogenetic cause of syndromic Autism Spectrum Disorder (ASD); up to 60% of males with FXS meet criteria for ASD. Furthermore, around 30%- 35% of children with WBS meet criteria for ASD. WBS has been considered for a long time as the polar opposite of ASD, given their hypersociable phenotype and their abnormal interest in social engagement. Nonetheless, recent researches have emphasized similarities between ASD and WBS phenotypes. By following Vivanti social abnormalities in ASD and WS can be characterized in terms of analogous difficulties in social cognition (the ability to read others' behaviour), and distinct patterns of social motivation (the propensity for social approach/engagement) which appears to be reduced in ASD and enhanced in WS. More than opposite condition, VIvanti suggests that WBS and ASD could share the same difficult in comprehension of social relationship, with opposite pattern of social engagement (enhanced in WBS and weakened ASD). Moreover, some researches showed that children with WS were similarly delayed in global adaptive functioning when compared to ones with ASD. Given, these similarities authors suggest to test the feasibility and validity of therapy for ASD in children with WBS. Parent Mediated Therapy (PMT) is a group of technique-focused interventions where the parent is the agent of change and the child is the direct beneficiary of treatment. Italian Guidelines for ASD highlight the importance of PMT for ASD treatment. PMT is also strongly recommended by NICE Clinical Guideline CG170 and WHO Mental Health Gap Action Program. PMT has showed evidence of effectiveness in short and long-term symptom reduction in young children with ASD. A research project on the effectiveness of PMT for children with ASD has been activated since 10 years at the Bambino Gesù Children Hospital (BGCH) in Rome. In last years, a semi-manualized intervention called Cooperative Parent Mediated Therapy (CPMT) has been systematized. Following Bearss' Parent Training taxonomy, CPMT is a targeted parent-mediated intervention focused on the ASD core symptoms. CPMT is based on the most significant models of parent training for ASD, in the perspective of Naturalistic Developmental Behavioral Interventions-NDBI with specific attention to the promotion of cooperative interactions. The aim of CPMT is to improve parental skills, to enable parents promoting the following seven target skills in their child: socio-emotional engagement, emotional regulation, imitation, communication, joint attention, play and cognitive flexibility and cooperative interaction. An individualized treatment plan is designed for each child in order to determine his developmental level and treatment goals. CMPT usually last 6 months, for a total amount of 15 sessions of 90 min; twelve core sessions (one session per week) are delivered in the first 3 months, followed by 3 monthly booster sessions. Each weekly core session had a specific focus and specific intervention strategies based on active parent coaching during parent-child interaction, and included the parent-child dyad with the parent being actively coached by a trained therapist. Live active coaching increases parents' competence in implementing strategies to enhance child development, and at the same time increases their confidence. This intervention has demonstrated evidence of effectiveness in socio-communicational improvement as measured by ADOS-G in a randomized controlled trial (RCT). On this purpose, some recent researchers have extended the use of PMT to children with genetic disorders and autistic features, such as Fragile X Syndrome (Vismara et al., 2019). While showing encouraging results, the samples of research were limited (four participants); moreover, parent coaching took place mainly through digital services (e.g. video call). Authors suggest implementing RCTs with larger samples in order to evaluate validity of PMT for individuals with FXS. Moreover, as far as we know, there are currently no researches of PMT in patients with WBS.~Since 2017, an experimental, non-pharmacological, randomized, controlled monocentric and non-profit study was started at BGCH in order to verify effectiveness of CPMT for socio-communicative deficit in children with FXS and WBS. Our hypothesis is that CPMT, in addition to conventional rehabilitation therapies (mainly speech therapy and occupational therapies), could contribute to the enhancement of socio-communicative skills and the reduction of behavioural problems. We also expected also an improvement in family quality of life and a reduction of parental stress. The intervention is provided by psychologists with specific training and expertise in CPMT and monitored through supervision by a senior child psychiatrist~Assessment: Children and their family will be evaluated at two time-points, pre randomization (T0) and six months later, at the end of control/treatment period (T1), by means of following assessment tools :~Children: 1. Cognitive Level: Leiter 3/Griffiths III; appropriate tool will be used by evaluation of developmental level 2. Adaptive Level: Vineland Adaptive Behavior Scales, Second Edition; 3. Socio-communication skills: Early Social Communication Scales; the questionnaire Skills Socio-Conversational of the Child (Le abilità socio-conversazionali del bambino; ASCB) ; 4. Language level: Italian adaptation of MacArthur-Bates Communicative Development Inventories. - Il Primo Vocabolario del Bambino; 5. Behavioural problem: Child Behavior Checklist; 6. Clinical improvement: Clinical Global Impression - Severity scale; Clinical Global Impression - Improvement scale~Parents: 1. Parental Stress: Parenting Stress Index-Short Form; 2. Parental Quality of Life: WHO Quality of Life

Fragile X Syndrome (FXS) and Williams-Beuren Syndrome (WBS) are relatively rare disorders characterized by developmental delay associated to socio-communicative deficit and autistic-like behaviours.~WBS has been considered for a long time as the polar opposite of ASD, given their hypersociable phenotype. Nonetheless, recent researches have emphasized similarities between ASD and WBS phenotypes. By following some authors social abnormalities in ASD and WS can be characterized in terms of analogous difficulties in social cognition), and distinct patterns of social motivation which appears to be reduced in ASD and enhanced in WBS. More than opposite condition, these authors suggests that WBS and ASD could share the same difficult in comprehension of social relationship, with opposite pattern of social engagement (enhanced in WBS and weakened ASD). Given, these similarities authors suggest testing the feasibility and validity of therapy for ASD in children with WBS. Parent Mediated Therapy (PMT) is a group of technique-focused interventions where the parent is the agent of change and the child is the direct beneficiary of treatment. PMT demonstrated evidence of effectiveness in socio-communicational improvement for children with ASD in a randomized controlled trial (RCT).~Some recent researchers have extended the use of PMT to children with genetic disorders and autistic features, such as FXS. While showing encouraging results, the samples of research were limited.~They main aim of this research is to to verify effectiveness of Cooperative PMT (CMPT) for socio-communicative deficit in children with FXS and WBS. Our hypothesis is that CPMT, in addition to conventional rehabilitation therapies (mainly speech therapy and occupational therapies), could contribute to the enhancement of socio-communicative skills and the reduction of behavioural problems. We also expected also an improvement in family quality of life and a reduction of parental stress.

The aim of the proposed project is to identify new risk indicators of PFO. The evaluation of the R-L shunt is based on the newly developed precise measurement technique. Moreover, this measurement of R-L shunt is feasible in a case when R-L shunt is present only intermittently.~Detection and quantification of R-L shunt will be realized by the original INNTHERM® ® system (Innova Medical s.r.o., Velká Dobrá). This system is based on the principle of thermodilution.~The basic assumption of our study is the hypothesis, that the size of the R-L shunt (and especially its maximum size during intra-abdominal pressure increase) is a risk factor for the development of paradoxical embolism (from pulmonary to systemic circulation). The most critical consequence of paradoxical embolism is the development of ischemic stroke.~Such measurement with an unequivocal accuracy has never been done so far, due a lack of technology precise enough.~Precise quantification of R-L shunt will allow a more accurate prediction of high-risk patients, especially after correlation with commonly used methods. PFO is now an indication for implantation of percutaneous occlusion device only in case of secondary prevention of stroke, i.e. in a group of patients who have had an ischemic stroke.~Prospectively, precise and better identification of a risk group of these patients could lead to cost reduction of treatment. This cost reduction is crucial for young working-age patients who can be treated before a major irreversible brain injury occurs.~A parameter applicable in primary prevention saves the cost of ischemic stroke treatment and other systemic embolism; additionally it will contribute to cost reduction during aftercare treatment.

The aim of the project is to identify new risk indicators of PFO. The evaluation of the R-L shunt is based on the newly developed precise measurement technique. Moreover, this measurement of R-L shunt is feasible in a case when R-L shunt is present only intermittently. Multicentric study with 150 patients.

This study plans to compare a direct antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) obtained by mid-turbinate nasal swab with a reverse transcription polymerase chain reaction (rt-PCR) test obtained by nasopharyngeal swab (the current reference standard) in a population of patients with symptoms suggestive of COVID-19 for fewer than 5 days. Subjects whose physicians have already ordered an rt-PCR test at a Carilion testing center will be screened and recruited by phone during a required scheduling call. The study coordinator will describe the study by phone, and the subject will be consented when they arrive at the testing center. After consenting, a mid-turbinate swab direct antigen test will be obtained just prior to the ordered nasopharyngeal swab and any other ordered tests. The subjects will receive their rt-PCR test results through the usual channels of clinical notification. The subjects will not receive their nasal antigen results. The antigen test results will be analyzed in a batch process and the results entered into RedCap by the study staff. The rt-PCR results will be extracted from the Epic electronic health record using patient identifiers and paired with the corresponding antigen result for statistical analysis.

A comparison of a direct antigen test for SARS-CoV-2 obtained by mid-turbinate swab with the reference standard rt-PCR test obtained by nasopharyngeal swab in outpatients with symptoms compatible with COVID-19.

Infection with severe acute respiratory syndrome-CoV-2 (SARS-CoV-2) may be asymptomatic or associated with life-threatening interstitial pneumonia. Clinically, patients affected from severe coronavirus disease-19 (COVID-19) are described as exhibiting rapidly progressing acute respiratory failure with unusually low oxygen levels in arterial blood. On computed tomography scans, diffuse, peripheral ground glass opacities of the lung are seen while autopsy lung specimens showed diffuse alveolar damage and capillary endothelialitis.~The objective of the current study, conducted in patients who had recovered from mild-to-severe COVID-19 illness, was to test that simultaneously-determined lung diffusing capacity for nitric oxide (NO) and carbon monoxide (CO) may be of great use to early detect post-infective diffusive gas exchange abnormalities. More specifically, we hypothesized that measurement of membrane diffusive conductance for CO and pulmonary capillary volume may provide accurate information on residual changes of peripheral gas exchanging units of the lung related to previous SARS-CoV-2 infection.

Infection with severe acute respiratory syndrome-CoV-2 (SARS-CoV-2) may be associated with diffuse alveolar damage and pulmonary vasculitis. Thus, it is likely that pulmonary function changes may be seen in COVID-19 survivors. The aim of the present study was to test that simultaneously-determined lung diffusing capacity for nitric oxide and carbon monoxide may be useful to detect post-viral diffusive gas exchange abnormalities early after mild-to-severe COVID-19-related pneumonias.

The objective of the study is to evaluate the safety and efficacy of (MTX -LDE) in patients with mild Coronavirus-19 (COVID-19) disease.~In phase 1, firstly 3 patients with moderate COVID-19 disease will receive MTX-LDE IV 15mg each 7 days, up to 3 times, during hospitalization. After that, 9 patients with moderate COVID-19 disease will receive MTX-LDE IV 30mg each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of adverse events.The purpose of this phase will be evaluate safety and pharmacokinetics.~If no objection by data and safety monitoring board (DSMB), will be authorized to start the second phase.~In phase 2, 88 patients with moderate COVID-19 disease will be randomized to receive MTX-LDE IV 30mg or placebo-LDE IV each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of any trial endpoints or other adverse events.The primary endpoint of this phase will be reduction in duration of hospitalization stay between groups.~Patients will undergo clinical and laboratory safety evaluations daily. An algorithm for drug suspension based on clinical and laboratory finding will be followed.

The investigators propose a prospective, randomized, double-blind, placebo-controlled study, conducted in two phases. The purpose of the study is to evaluate the safety and efficacy of methotrexate in a cholesterol-rich non-protein nanoparticle (MTX -LDE) in adults diagnosed with mild Coronavirus-19(COVID-19) disease.~A total of 100 patients will be randomized to receive MTX-LDE or placebo each 7 days, up to 3 times, during in hospital treatment.

Chronic kidney disease (CKD) is considered a global public health problem, which affects approximately 10% of the world population. Due to partial or total loss of kidney function, the patient needs renal replacement therapy, with hemodialysis (HD) being the therapy most used, having a prevalence of up to 93.1% in Brazil. The restrictions imposed by CKD and the treatment of prolonged HD negatively affect health, increasing stress and decreasing the quality of life (QoL). The restrictions imposed by CKD and the treatment of prolonged HD negatively affect health, increasing stress and decreasing the QoL. Hemodialysis supports life and relieves a series of symptoms; however, it imposes many limitations. Social, financial and family stressors are numerous when dealing with the symptoms of the disease, restrictions and treatment prescriptions. Research shows positive results from Mindfulness-Based Interventions (MBIs) in reducing symptoms of different chronic diseases and mental and physical disorders such as: depression, anxiety, hypertension, cancer, chronic pain, cardiovascular diseases, insomnia, addictive behaviors, and kidney disease, and in improving medication adherence. This is an incipient field of research at the international level and almost nonexistent in Brazil. Evidence indicates the need for MBIs to be performed during HD sessions, adapted to the context, to facilitate patient compliance, contribute to the management of the discomfort generated during HD and promote health. This project has as main objectives to develop and evaluate the effects of a mindfulness-based intervention in the reduction of stressors, pain and quality of life of people undergoing hemodialysis. For this purpose, a randomized controlled pragmatic study with random allocation and blinding of the outcome evaluator will be performed, using quantitative and qualitative measures evaluated within 6 months after the intervention. The results of this research could form a consistent basis for a new and promising field of research that could contribute to improving the health of people undergoing hemodialysis and other populations that need long-term hospital care.

This project has as main objective to evaluate the effects of a Mindfulness-based intervention (MBI) in the reduction of stressors, pain and quality of life of people with chronic kidney disease undergoing hemodialysis (HD). The investigators hypothesize that this program offered during hemodialysis sessions may modify the pain profile, stressors levels and may improve the quality of life by the people in hemodialysis. This is an incipient field of research at the international level and almost nonexistent in Brazil. Evidence indicates the need for MBIs to be performed during HD sessions, adapted to the context, to facilitate patient compliance, contribute to the management of the discomfort generated during HD and promote health.

Forensic patients often display deficits in executive functions, namely difficulties in planning, strategic thinking, problem-solving, and inhibiting inappropriate behavior. Such deficits are transdiagnostic and often underlie behavioral incidents, undermine reintegration into the community, and increase recidivism risk. Despite this, forensic programs usually do not include executive function training.~One approach to train executive functions is cognitive remediation, which consists of behavioral exercises engaging cognitive skills, supported by coaching. In various mental health conditions, cognitive remediation has been repeatedly associated with improvements in cognitive, functional, and clinical outcomes, with small-to-moderate effect sizes. Thus, it should be clarified whether this approach can lead to similar improvements in forensic populations.~In the present trial, we will investigate whether 12 hours over 6 weeks of computerised cognitive remediation administered using tele-health can improve executive functions relative to an active control condition in a sample of 30 forensic inpatients (Aim 1). We will further examine the effect of cognitive remediation (vs. active control) on other variables that are critical for forensic rehabilitation, namely oppositional behaviour, functional capacity, and mental health symptoms (Aim 2). Lastly, we will explore whether any effects persist 12 weeks following cognitive remediation (Aim 3).~Cognitive remediation is an evidence-based inexpensive training method that could be integrated into forensic healthcare practice. In the long term, the expected cognitive, functional, and clinical improvements associated with cognitive remediation have the potential to result in shorter hospitalisations and reduced recidivism rates.

Forensic patients often display cognitive deficits, particularly in the domain of executive functions, that represent a challenge to forensic rehabilitation.~One empirically-validated method to train executive functions is cognitive remediation, which consists of cognitive exercises combined with coaching.~This trial investigates whether cognitive remediation can improve cognitive, functional, and clinical outcomes in forensic inpatients.

Sepsis results in an intensive interaction between Inflammation and the coagulation system. The activation of the coagulation system leads to consumption of procoagulatory as well as anticoagulatory proteins and platelets. This process may induce microcirculatory thrombosis as well as hemorrhagic diathesis, which is commonly described as disseminated intravascular coagulation (DIC).~The International Society on Thrombosis and Haemostasis (ISTH) recommends the use of the DIC score to describe this syndrome. A score of at least 5 points is defined as an overt DIC. However, the DIC score does not allow to differentiate between a hypercoagulation and hypocoagulation states and whether there could be a difference regarding outcome between the two states.~In this prospective observational study, patients admitted to a medical intensive care unit will be included. The DIC score as well as rotational thromboelastometry (ROTEM) will be evaluated within the first 24 hours after the diagnosis of sepsis as well as on day 3 and 5.

Sepsis results in activation of the coagulation system, which is commonly described as disseminated intravascular coagulation (DIC). The DIC score, which is commonly used to define this syndrome, does not allow to delineate between hypercoagulation and hypocoagulation. The aim of this prospective observational study is to evaluate data from automated rotational thromboelastometry and compare These with the DIC score regarding intensive care unit outcome.

The investigators will recruit participants between the age of 18 and 65 with chronic non-specific low back pain and a sedentary lifestyle. The partcipants will be randomly assigned to one of the three groups. The first group is the control group, the participants will be asked to not change their daily routine. In the first intervention group sedentary behaviour will be reduced. The participants will be asked to download an app on their smartphone and computer. This app will ask the participants to stand up and walk during 2 minutes to interrupt their sedentary behaviour during working hours. In the second intervention group participants will be asked to increase their physical activity. More specifically the participants will be asked to be active for a period of 150min/week. The intervention takes place over a period of 6 weeks. During these 6 weeks the participants needs to wear an accelerometer the first and the last week of the intervention. The week before the intervention a pre-measurement will take place, this means that the participant needs to wear an accelerometer during a week, fill out a questionnaire (BPI and SF-36) and the pressure pain threshold will be measured. After the intervention (6 weeks) the pressure pain threshold will be measured, average steps will be measured (accelerometer) and a questionnaire needs to be filled out. These results will be compared to the results before the intervention and to the results of the other groups. With this study the investigators will investigate whether less sedentary behavior or more physical activity are beneficial for chronic low-back pain.

The investigators will recruit participants between the age of 18 and 65 with chronic non-specific low back pain and a sedentary lifestyle. The participants will be randomly assigned to one of the three groups. The first group is the control group, the participants will be asked to continue their daily routine. The second group is an intervention group, sedentary behaviour will be reduced. In the third group participants will be asked to increase their physical activity up to 150min/week. The intervention takes place over a period of 6 weeks. After the intervention the pressure pain threshold will be measured, average steps will be measured (accelerometer) and a questionnaire needs to be filled out. These results will be compared to the results before the intervention and to the results of the other groups.

Study was cancel due to principle investigator had been resigned

Study was cancel due to principle investigator had been resigned

Rationale T-cell therapy is an experimental personalized immunotherapy where TILs are isolated from the patient's own tumor tissue, expanded in vitro to billions of cells and then administered to the individual patient with the purpose of eliminating the remaining cancer cells. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine phosphate is administered to the patient before TIL infusion to reduce the number of irrelevant immune cells.~In two consecutive pilot trials at National Center for Cancer Immune Therapy (CCIT-DK), it has been shown that adoptive cell therapy (ACT) with TILs for patients with advanced ovarian cancer (OC) is feasible and tolerable. In the most recent of these trials ACT was combined with a CTLA-4 inhibitor, Ipilimumab and a PD1-inhibitor, Nivolumab.~Between 90-100% of infused T-cells in these previous ovarian cancer ACT trial expressed LAG-3. The interaction between LAG-3 on T-cells and MHC-II on tumor cells inhibits T-cell function.~In this phase I/II study 18 patients with advanced ovarian -, fallopian tube-, and primary peritoneal cancer will be included. Included patients undergo surgical removal of tumor tissue for tumor-infiltrating lymphocyte (TIL) manufacturing. Lymphodepleting chemotherapy is administered prior to TIL infusion. Hereafter the patients are treated with the programmed cell death protein 1 (PD-1) antibody Nivolumab and the anti-lymphocyte activation gene 3 (anti-LAG-3) antibody Relatlimab. The study will be devided into 3 steps.~Step One (6 subjects): Patients are treated without prior administration of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody Ipilimumab pre-tumor harvest.~Step Two (6 subjects): If Step One proves feasible and tolerable patients in Step Two will receive one dose of Ipilimumab pre-tumor harvest.~Step Three (6 subjects): Patients are treated either with or without prior Ipilimumab pre-tumor harvest depending on the tolerability data from Step Two.~All patients are treated with lymphodepleting chemotherapy for 7 days followed by infusion of TILs. For safety reasons no IL-2- will be administered in this study~The aim of this study is to demonstrate that ACT and a combination of Relatlimab-Nivolumab does not increase the toxicity compared to the same treatment regimen including Nivolumab monotherapy. The study will elucidate whether the combination Relatlimab-Nivolumab lead to objective responses and improves progression free survival (PFS). It is anticipated that combining Relatlimab and Nivolumab with Adoptive T cell therapy (ACT) for advanced OC is safe and feasible. Further, it is hypothesized that the combination will lead to improved immunity in tumor and blood as well as improved antitumor efficacy.~Objectives~To evaluate the tolerability and safety of the treatment~To characterize antitumor immune responses and clinical efficacy

Although immunotherapy has revolutionized the treatment of many cancers, ovarian cancer patients have not yet benefitted from the advances.~In two consecutive pilot trials at National Center for Cancer Immune Therapy (CCIT-DK), is has been have shown that adoptive cell therapy (ACT) with TILs for patients with advanced ovarian cancer (OC) is feasible and tolerable. In the most recent of these trials ACT was combined with a CTLA-4 inhibitor, Ipilimumab and a PD1-inhibitor, Nivolumab. Only transient clinical responses where observed.~Between 90-100 % of infused T-cells in our previous ovarian cancer ACT trial expressed LAG-3. The interaction between LAG-3 on T-cells and MHC-II on tumor cells inhibits T-cell function.~In this study adding the LAG-3 antibody Relatlimab to the ACT-regimen described above may therefore well unleash T-cell antitumor efficacy by blocking the known LAG-3-MHC-II interaction.~With this study the aim is to demonstrate that adding the lag-3-inhibitor Relatlimab to the above treatment regimen is feasible and tolerable. The study will elucidate whether the combination Relatlimab-Nivolumab leads to objective responses and improves progression free survival (PFS).

This study is an open-label, non-randomized dose escalation and expansion study of the LSD inhibitor SP-2577 in combination with the anti PD- 1 antibody pembrolizumab in patients with advanced, recurrent small cell ovarian cancer of the hypercalcemic type (SCCOHT) as well as select additional ovarian and endometrial cancers with mutations in the genes within the SWI/SNF pathway (Ovarian Clear Cell Cancers (OCCC), Endometrioid Ovarian Cancers (EOC) and Endometrioid Endometrial Cancers (EEC).

Open-label study of SF-2577 plus pembrolizumab in advanced, recurrent small cell ovarian cancer as well as select additional ovarian and endometrial cancers within the SWI/SNF pathway.

This is a Phase 3, prospective, randomized, double-masked, two-arm, multi-center non-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with treatment-naïve DME.~The primary endpoint will be assessed at Year 1; additional secondary endpoints for efficacy will be assessed at Years 1 and 2.

This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.

Cardiovascular disease, and especially myocardial infarction, is the most common cause of death globally, and is particularly common in older individuals. Practical measures that can reduce both the prevalence and incidence of cardiovascular disease are of great value. It is well known that regular physical activity has a protective effect against the development of cardiovascular diseases such as acute myocardial infarction. Therefore, the American Heart Association also recommends ≥ 30 min. per day five days a week. It has been shown that physical activity can improve the function of the heart and blood vessels, but it is less well known how physical activity can affect the risk of formation of dangerous blood clots, and thus the risk of heart attack and stroke.~In a cross-sectional study it has been shown that a physically active lifestyle can reduce the risk of blood clot formation, but experimental evidence for the importance of a period of physical activity for the risk of blood clot formation is lacking. New methods have been set up for measuring the coagulation profile. The analyzes are performed on a blood sample and allow a thorough determination of platelet reactivity as well as an innovative measure of how the microstructure of a possible blood clot would develop. In this project, these methods is used to examine how physical activity, in the form of team sports, affects the coagulation profile of elderly men and women.~The increasing age-related risk of cardiovascular disease is associated with endothelial dysfunction and decrease in capillary density, and it has been shown that initiation of capillary growth is a successful method to treat cardiovascular disease. Therefore, this project will also investigate how a longer period of physical activity, in the form of team sports, affects capillary density and endothelial function in men and women aged 60-70 years. Both men and women will be recruited, as it is still unknown whether men and women respond differently to physical activity in relation to coagulation profile, susceptibility to blood clots and capillary density.~Part of the novelty of this present study consist of 1) linking the clinical measurements with data on sickness absence, disease development, etc. and with data on the underlying mechanisms, 2) examining the short-term effect (16 weeks) and the long-term effect (up to 2 years) of physical activity, in the form of team sports in a municipality setting, on coagulation, risk of blood clots, capillarization and endothelial function in general in the elderly, as well as 3) investigate whether there is a difference in the aforementioned measurements in men and women.

Cardiovascular disease, and especially myocardial infarction, is the most common cause of death globally, and is particularly common in older individuals. Practical measures that can reduce both the prevalence and incidence of cardiovascular disease are of great value. It is well known that regular physical activity has a protective effect against the development of cardiovascular diseases such as acute myocardial infarction. It has been shown that physical activity can improve the function of the heart and blood vessels, but it is less well known how physical activity can affect the risk of formation of dangerous blood clots, and thus the risk of heart attack and stroke.~In a cross-sectional study it has been shown that a physically active lifestyle can reduce the risk of blood clot formation, but experimental evidence for the importance of a period of physical activity for the risk of blood clot formation is lacking. New methods have been set up for measuring the coagulation profile. The analyzes are performed on a blood sample and allow a thorough determination of platelet reactivity as well as an innovative measure of how the microstructure of a possible blood clot would develop. In this project, these methods is used to examine how physical activity, in the form of team sports, affects the coagulation profile of elderly men and women.~The increasing age-related risk of cardiovascular disease is associated with endothelial dysfunction and decrease in capillary density, and it has been shown that initiation of capillary growth is a successful method to treat cardiovascular disease. Therefore, this project will also investigate how a longer period of physical activity, in the form of team sports, affects capillary density and endothelial function in men and women aged 60-70 years. Both men and women will be recruited, as it is still unknown whether men and women respond differently to physical activity in relation to coagulation profile, susceptibility to blood clots and capillary density.

Unrecognized wild-type transthyretin amyloidosis (ATTRwt) in patients with idiopathic carpal tunnel syndrome (CTS) is a prevalent aging-related disorder. Amyloid deposition in the tenosynovial tissue has been reported in ~35% of patients with idiopathic carpal tunnel syndrome.~Otherwise, CTS has been shown to be the most common initial symptom of systemic wild-type transthyretin amyloidosis. The clinical significance of subclinical ATTRwt deposits in the heart in elderly patients has yet to be determined, but these deposits could contribute to the development of heart failure with preserved ejection fraction. ATTRwt has been reported in ~15% of patients with heart failure with preserved ejection fraction. Early detection of amyloid deposition in the transverse carpal ligament of patients with CTS could anticipate cardiac damage and progression to heart failure.The aim of this study is to determine the prevalence of transthyretin amyloidosis in pathology of the transverse carpal ligament and cardiac involvement using natriuretic peptides, electrocardiography and echocardiography in patients referred for carpal tunnel release surgery of idiopathic carpal tunnel syndrome.

This study will determine the prevalence of transthyretin amyloidosis in pathology of the transverse carpal ligament and cardiac involvement using natriuretic peptides, electrocardiography and echocardiography in patients referred for carpal tunnel release surgery of idiopathic carpal tunnel syndrome. This study will describe the relationship between amyloid deposition observed on the transverse carpal ligament and the presence of cardiac involvement.

In December 2019, China reported cases of acute respiratory disease caused by a new beta-coronavirus (SARS-CoV-2), called COVID-19 by the WHO. In January 2020 this entity issues an alert about the emergence of this new disease throughout the world, and in March it declares it a pandemic. Severe cases represent around 14-20% of those reported, and admission to the ICU is highly variable according to the different publications and severity of disease, ranging between 29% and 89%. The mortality reported in these publications ranges between 1.4 and 42%; with the development of acute respiratory distress syndrome (ARDS) being one of the most severe complications, associated with worst outcomes. However, the time of appearance of symptoms of severe acute respiratory failure has shown significant variability between these studies, with a median appearance of 2, 5 and 14 days from the onset of symptoms of the disease.~As of March 21, 2020, cases in Latin America were increasing, finding countries such as Brazil, Chile, Ecuador, Peru and Argentina among the countries with the highest number of confirmed cases, being classified as countries with local transmission. Since there is no information about on the behavior of this new disease in our country, the Argentine Society of Intensive Care (SATI) launched an epidemiological study to know the characteristics, risk factors and evolution of the most severely compromised patients with COVID-19, those admitted to the ICU requiring mechanical ventilation (MV).~Therefore, the main objective of the present study is to determine the ICU and in-hospital mortality associated with COVID-19 infection and its independent predictors, in patients admitted to adult ICUs in Argentina on MV.~Secondary objectives include: determining epidemiological and clinical data and mechanical ventilation management in patients with COVID-19 , support and therapeutic measures implemented by their assistant physicians, and the evolution and complications developed by these patients during their ICU stay. The different causes of death will also be recorded.~Likewise, characteristics of each ICU will be recorded, and a survey will be carried out on the management of the COVID-19 pandemic, which will require information on the additional availability of critical resources for the care of patients admitted to the ICU. The opinion about the management of the pandemic by the different governmental strata will be required, in order to detect possible points of improvement in the external management of the pandemic.

The main objective of the present study is to determine ICU and in-hospital mortality associated with COVID-19 infection and its independent predictors, in patients admitted to adult ICUs in Argentina with a requirement for mechanical ventilation.~Secondary objectives include: determining epidemiological and clinical data in patients with COVID-19 disease; the associated morbidity, the support and therapeutic measures implemented, and the evolution of these patients upon discharge from the ICU.~Likewise, characteristics of each ICU will be recorded, and a survey will be carried out on the management of the COVID-19 pandemic, which will require information on the additional availability of critical resources for the care of patients admitted to the ICU. Likewise, characteristics of the ICU and hospitals will be registered.

Globally, breast cancer is one of the most prevalent cancers in women and is the second leading cause of cancer death , representing 15% of worldwide deaths per year. In Egypt, it accounts for 32 % of cancer in women with a high mortality rate.~The etiology of breast cancer is multifactorial in which multiple epigenetic and genetic variations affect its incidence and prognosis . Although diagnostic methods and therapeutic strategies for breast cancer have been improved in past decades, long-term survival of breast cancer patients still remains poor due to high proliferation, metastasis and post-surgical recurrence rate.~Therefore, it is critical to develop more effective screening methods that can detect BC at an early stage and novel therapeutic targets for better treatment. This may be achieved by understanding the molecular mechanisms underlying the initiation and progression of this malignancy.~Complement C1q tumor necrosis factor-related protein (CTRPs) are a protein family of adiponectin paralogs which contains fifteen members, CTRP1- CTRP15. This super family are involved in several biological processes, including metabolism, immunity, inflammation, apoptosis and cell differentiation (15, 16). Accumulating evidence correlates CTRP family members with carcinogenesis and signaling pathways associated with cancer development, progression and metastasis.~C1q tumor necrosis factor-related protein 6 (CTRP6) or (C1qTNF6) is a member of CTRPs family. It contains four domains including signal peptide, short N-terminal variable region, collagen domain and C-terminal C1q domain. It is expressed mainly in placenta, heart, uterus and adipose tissue.~CTRP6 is involved in multiple physiological processes, such as regulating cell proliferation and differentiation. It also mediates fatty acid oxidation, adipogenesis and insulin sensitivity, attenuates cell fibrosis and displays anti-inflammatory properties.~Although recent studies have revealed that adiponectin has an inhibitory role in carcinogenesis, the role of CTRP6 in carcinogenesis remains unclear. CTRP6 was initially found to be overexpressed and possibly contributes to tumor angiogenesis in many hepatocellular carcinomas. Moreover, recent research indicates that CTRP6 is correlated with gastric cancer progression by mediating proliferation, migration and apoptosis, which reveals a similar pattern in lung adenocarcinoma.~However, tumor suppressor functions of CTRP6 were also successively reported. CTRP6 was found to have inhibitory effect on the proliferation and migration of ovarian cancer cells. Moreover, CTRP6 significantly suppressed the growth and invasion activity of the oral squamous cell carcinoma cells.~The role CTRP6 plays in breast cancer is yet unknown. The present study will investigate the level of CTRP6 in BC specimens. Furthermore, the pathological functions of CTRP6 in BC, including cell growth, proliferation, migration, and effect on inflammation and angiogenesis will be studied in breast cancer cells.

Globally, breast cancer is one of the most prevalent cancers in women and is the second leading cause of cancer death , representing 15% of worldwide deaths per year . In Egypt, it accounts for 32 % of cancer in women with a high mortality rate.

Study Population: 40 subjects with presenting with thumb basal joint arthritis over the age of 18 will be recruited from the UVA Hand Center.~Description of Sites/Facilities Enrolling Participants: This will be a single-site study conducted at the UVA Hand Center at the University of Virginia.~Description of Study Intervention: The study design will be a double-blind randomized control trial with crossover. Treatment will be blinded to the subjects and investigators. Patients will be randomly assigned 2 weeks of the case (CBD) or control cream and then crossover to the other cream for 2 more weeks. Patients will apply the topical cream at their thumb basal joint one time daily for 1 hour. The subjects will be advised to observe for physiologic changes, skin changes, or other adverse effects. If mild to serious adverse events are noticed, the creams will be removed immediately and appropriate care and observation will be taken. Each condition will last for 2 weeks and then subjects will be contacted by the study coordinator to facilitate crossover into the other condition. To capture any delayed-onset adverse events, including those related to skin changes that might develop after the drug is discontinued, subjects will attend a follow-up visit seven (7) days following the last dose of investigational cream.~Study Duration: This study will last one year from the beginning of subject recruitment to data analysis.~Participant Duration: Subjects will be enrolled in this study for approximately five (5) weeks from Screening until the final Study Visit.

Rationale: CBD is commonly being used as an over-the-counter treatment for arthritis-related pain, however no clinical trial has been performed to establish efficacy.~Hypothesis: CBD is more effective than placebo for relieving pain and improving patient-reported outcomes for thumb basal joint arthritis.~Study Design: The study design with be a double-blind, randomized controlled trial with crossover. Treatment will be blinded to the subjects and investigators. Patients will be randomly assigned 2 weeks of the CBD or control and then crossover to the other condition for 2 additional weeks. Patients will apply the cream at the thumb base twice daily for 1 hour. Subjects will be advised to observe for physiologic changes, skin changes, or other adverse effects.

Since the COVID-19 pandemic began, several psychological support programs for health care workers have been implemented, especially group or individual counseling sessions delivered face-to-face or using phones and video conferencing platforms. However, there are significant barriers to the delivery of such psychological initiatives. In this context, digital interventions to improve health services and care outcomes are recommended for implementing and providing remote psychological support.~Virtual reality can play a relevant role in providing psychological care to healthcare workers facing COVID-19. New commercial head-mounted display have made virtual reality accessible even to the mass audience, breaking down the barriers in the diffusion and use of this technology. Thanks to this fact, virtual reality can now be autonomously used by people and offered to provide psychological assistance remotely.~Within this context, this randomized controlled trial (RCT) aims to investigate the efficacy of a virtual reality home-based program for diminishing stress and anxiety in a sample of Italian healthcare workers involved in the COVID-19 pandemic. In particular, the objective is to compare the efficacy of this type of training with respect to the same program without virtual reality and a waiting list.

Since the COVID-19 pandemic began, several psychological support programs for health care workers have been implemented, especially group or individual counseling sessions delivered face-to-face or using phones and video conferencing platforms. However, there are significant barriers to the delivery of such psychological initiatives. In this context, digital interventions to improve health services and care outcomes are recommended for implementing and providing remote psychological support. Virtual reality can play a relevant role in providing psychological care to healthcare workers facing COVID-19. New commercial head-mounted display have made virtual reality accessible even to the mass audience, breaking down the barriers in the diffusion and use of this technology. Thanks to this fact, virtual reality can now be autonomously used by people and offered to provide psychological assistance remotely. Within this context, this randomized controlled study aims to investigate the efficacy of a virtual reality home-based program for diminishing stress and anxiety in a sample of Italian healthcare workers involved in the COVID-19 pandemic.

The worldwide COVID-19 pandemic has led to a dramatic increase in the number of patients hospitalized in intensive care units for an acute respiratory failure in all countries. This situation has quickly led to massive shortage in masks, mechanical ventilation machines and common medications such as hypnotics. The reasons for such shortage are multiple: dramatic increase of the demand, production discontinuation because of shutdowns in multiple countries, and withholding of products by producing countries. All countries over the world are currently experiencing a major shortage in basic hypnotic medications (propofol, midazolam) in the intensive care as well as in the operating theatre. Remimazolam is a novel benzodiazepine with a short half-life that has been administered in patients undergoing major surgery, as well as in the intensive care unit. The Principal Investigator proposes to perform a pilot study assessing the benefit-risk ratio of Remimazolam in the critical care units of Nantes University Hospital during the COVID-19 pandemic.

The worldwide COVID-19 pandemic has led to a dramatic increase in the number of patients hospitalized in intensive care units for an acute respiratory failure in all countries. This situation has quickly led to massive shortage in masks, mechanical ventilation machines and common medications such as hypnotics. All countries over the world are currently experiencing a major shortage in basic hypnotic medications (propofol, midazolam) in the intensive care as well as in the operating theatre. The Principal Investigator proposes to perform a pilot study assessing the benefit-risk ratio of Remimazolam (a novel benzodiazepine with a short half-life) in the critical care units of Nantes University Hospital during the COVID-19 pandemic.

Low back pain is a prevalent problem all over the World. low back pain prevalence is 84% by lifetime Chronic low back pain prevalence is 23%. Low back pain causing disability prevalence is also11% (1). Increasing sedentary lifestyle and obesity, aging of the population and inappropriate ergonomic work activities and working environment in the working society contribute to this increase (2).~Chronic low back pain is an important cause of labor losses and also it is the most common functional insufficiency under 45 years of age (3). Treatment approaches such as exercise and education in which the patient is actively involved in the treatment are recommended for the treatment of non-specific acute, subacute and especially chronic low back pain (4).~Whole body vibration (WBV), which is a new treatment method and applied through the device, is defined as mechanical repetitive motion or oscillatory motion occurring around a balance point (5). Chronic nonspecific low back pain is still a serious clinical, social and economic health problem. There are few studies and limited evidence evaluating the effectiveness of WBV exercises in chronic nonspecific low back pain. Different protocols are used for wbv exercise in studies (6). Our aim is to compare the effects of whole body vibration exercise modality on pain, functional recovery, laboor impact, quality of life with control group in patients with chronic nonspecific low back pain.~MATERYAL METHOD~This prospective, randomized and controlled study include 70 patients who were diagnosed chronic nonspecific low back pain. Patients were randomized into two groups using the 1:1 method. The first group was the treatment group in which applied the whole body vibration exercise and classical lumbar home exercise program. The second group (control) only received classical lumbar home exercise program.~Inclusion criterias are non-specific LBP (LBP other than those excluded, see exclusion criteria below) of a more than 3 months in patients aged 20 to 50 years, with average pain intensity evaluated Visaual Analog Scale (VAS) (1-10) that is higher than 5 Exclusion criterias are participants with likely specific causes of LBP This includes exclusion of history of malignancy, history of recent spinal surgery, dislocation, fracture, rheumatoid arthritis and ankylosing spondylitis and history of weakness of lower extremity or loss of sensation in lower extremity. Additionally, current pregnancy, , lactation, uncontrolled hypertension and history of diagnosed mental health conditions that would limit adherence to the trial procedures will be excluded.~Patients in the TVT exercise group; 24 sessions of TVT exercise 3 days a week (with at least 1 day of rest between each session) was performed under the supervision of a physician for a total of 8 weeks. . The vibration was given by the Power Plate® (pro5TM; Power Plate North America, Inc., Northbrook, IL, USA) device where a three-plan oscillation took place (most vertical, Z-axis).The Istanbul Low Back Pain Disability index is a self-reported measure of functional disability . The Istanbul Low Back Pain Disability index has reliability and validit(7). Quality of life was assessed using Short form-36 (SF-36). SF-36 is a widely used and validated scale in assessing quality of life. It is not specific to any disease group. Health and Labor Questionnaire (HLQ) was used in our study to evaluate job performance. HLQ is designed to collect quantitative data on the treatment of disease and its relationship to work performance. Intercultural adaptation was made to Turkish. HLQ data allow to estimate the production losses (costs) of paid and unpaid labor (8).

Whole body vibration (WBV), which is a new treatment method and applied through the device, is defined as mechanical repetitive motion or oscillatory motion occurring around a balance point (5). Chronic nonspecific low back pain is still a serious clinical, social and economic health problem. There are few studies and limited evidence evaluating the effectiveness of WBV exercises in chronic nonspecific low back pain. Different protocols are used for wbv exercise in studies (6). Our aim is to compare the effects of whole body vibration exercise modality on pain, functional recovery, laboor impact, quality of life with control group in patients with chronic nonspecific low back pain.

The EPICD-PCD is hosted at the Institute of Social and Preventive Medicine (ISPM) at the University of Bern, Switzerland. Research is performed in close collaboration with all data contributors. This study aims to characterise ENT disease in PCD patients and its association with lower respiratory disease, and to identify determinants of its prognosis.~The investigators aim to:~Assess the prevalence and severity of sinonasal and otologic symptoms and the frequency and range of signs and physiological findings assessed during standardised ENT physical examination, and describe differences by age;~Study the association of sinonasal and otologic disease with lower respiratory disease in PCD patients;~Identify determinants of disease course and prognosis of sinonasal and otologic disease in PCD patients.~Study design:~The EPIC-PCD is a prospective observational clinical cohort study, set up as a multinational multi-centre study. It is embedded into routine patient care of participating reference centres for PCD and patients will keep being managed according to local procedures and guidelines.~Patients with PCD are followed regularly at each centre, at 3-month to 6-month intervals. Each patient undergoes a detailed ENT sinonasal and otologic examination by ENT specialists, at minimum once a year, during a programmed follow-up visit. Additional ENT examinations are performed if indicated during in-between follow-up visits. Patients will not be subjected to additional invasive measurements solely for the purposes of the study.~What information is collected:~The study collect clinical data from patients assessment at regular consultations at the outpatient clinics.~For the collection of clinical data, participating centres will use FOLLOW-PCD, a disease-specific form for standardised prospective data collection during routine clinical follow-up of PCD patients.~Study database:~The EPIC-PCD database is web-based, using the Research Electronic Data Capture (REDCap) platform developed at Vanderbilt University. REDCap is widely used in academic research and allows data entry and extraction in various formats.~How to participate:~Centres that wish to participate to the project and contribute data can contact the EPIC-PCD managing centre to sign a data delivery agreement. They then will receive a password to access the online software REDCap and they will be able to enter their data directly. They can also upload follow-up data or add additional patients at a later time point.~Funding:~The setting up of the EPIC-PCD (salaries, consumables and equipment) was funded by the Swiss National Science Foundation. Data collection and management at each site was funded according to local arrangements. Most participating researchers and data contributors participate in the European Respiratory Society Clinical Research collaboration Better Evidence to Advance Therapeutic options for PCD (BEAT-PCD) (https://beat-pcd.squarespace.com/). Infrastructure is provided for free by the University of Bern, where the data are pooled and stored.

The Ear-Nose-Throat (ENT) Prospective International Cohort of patients with Primary Ciliary Dyskinesia (EPIC-PCD) is a prospective observational clinical cohort study, set up as a multinational multi-centre study. It is embedded into routine patient care of participating reference centres for PCD and patients keep being managed according to local procedures and guidelines.

Postoperative pain is an important clinical concern and quality-of-care metric, yet it is undertreated in neurosurgical patients. Approximately 40% of inpatients complain of severe pain postoperatively, and only 56% of these patients indicate that their pain is well controlled. In addition, pain is a common cause of delayed discharge and unplanned hospital readmission.~Pituitary adenoma is the second most common benign primary central nervous system tumor, and transnasal transsphenoidal (TTS) has long taken over craniotomy to be the first-line surgical approach for pituitary tumor resection. TTS significantly reduces patient's surgical trauma, shortens the operation time, reduces surgery-related complications, and increases total tumor resection rate compared with the previously used craniotomy. However, given that the nasal mucosa is extremely sensitive, the feeling of pain is more obvious after surgery via TTS approach than via craniotomy.~Opioids such as morphine and pethidine are the most effective post-surgical analgesics, but they have a series of side effects, such as drug addiction, decreased gastrointestinal motility, nausea and vomiting. Opioids are not an analgesic that must be used after TTS surgery. NSAIDS, such as parecoxib and lexone, and tramadol are also commonly used analgesics after surgery, and they are also effective. NSAIDS is a first-tier painkiller, and tramadol is a second-tier drug. There is no evidence-based evidence recommending the preferred choice of these two drugs. Which of NSAIDS and tramadol has the better analgesic effect and which drug brings lower side effects to patients is still unclear. The clinical application of the two drugs is entirely based on the personal habits of the surgeon.~Therefore, we plan to conduct a prospective randomized controlled trial to explore: whether the analgesic effect of NSAIDS is non-inferior than tramadol; and whether the side effects of NSAIDS are not higher than tramadol. This result will guide us in clinical pain management for patients with pituitary adenomas after surgery via TTS approach.

We hypothesize that the effects of non-steroidal anti-inflammatory drugs (NSAIDS) for pain relief among patients with pituitary adenomas undergoing transnasal transsphenoidal surgeries are non-inferior to tramadol. We aim to launch a single-center randomized clinical trial to verify this hypothesis.

Retinal vasculopathy with cerebral leukoencephalopathy (RVCL) is a very rare and uniformly fatal genetic condition that affects the microvasculature, especially of the brain and eye. Symptoms begin in adulthood (usually in the mid-30s to early 40s) and include loss of vision, mini-strokes, and dementia. Other patients have suffered from microvascular disease involving the kidneys, osteonecrosis, and gut ischemia. Some of these features of microvascular occlusive disease resemble ischemic events that occur during sickle cell disease. Currently, there is no effective treatment for RVCL.~The goal of this study is to test the efficacy of RVCL patients treated with crizanlizumab, a humanized monoclonal anti-P-selectin antibody that prevents leukocyte adhesion to the vascular endothelium, thereby limiting risk of microvascular occlusion. P-selectin is mobilized to the surface of activated vascular endothelial cells and promotes leukocyte adhesion to the blood vessel wall. The Miner laboratory has preliminarily observed a correlation with levels of soluble P-selectin and the number of brain lesions in patients with RVCL. Since leukocyte adhesion to the vascular endothelium promotes microvascular occlusion, we will determine if crizanlizumab will help to limit ischemia and brain lesions in patients with RVCL. This may lead to the development of fewer ischemic brain and eye lesions.~Up to 20 RVCL patients will receive intravenous infusions of crizanlizumab 5 mg/kg at weeks 1 and 3. Thereafter, patients will receive crizanlizumab 5 mg/kg every 28 days for a total of 24 total months. Monitoring will include standard-of-care serial MRI as well as standard-of-care eye disease monitoring at pre-defined intervals. High-risk medication monitoring will include blood work monitoring (CBC/CMP) 1 month after initiation of treatment and every 3 months thereafter. Standard-of-care assessments will be performed including radiological and physical examinations as well as eye imaging and examinations. Patients will be followed for at least 2 years after completion of crizanlizumab administration.

This is a Phase 2 trial that will test the efficacy and safety of crizanlizumab for the treatment of retinal vasculopathy with cerebral leukoencephalopathy (RVCL), a very rare and uniformly fatal genetic condition that affects the microvasculature, especially of the brain and eye. There currently is no treatment for RVCL. A maximum of 20 patients will be enrolled.

The major clinical features of chronic pancreatitis include glandular (exocrine and endocrine) failure and pain. The former can usually be managed satisfactorily by replacement strategies (enzymes or insulin) to restore nutritional and metabolic stability. However, pain has remained a major clinical challenge and is present in up to 90% of patients and is the primary cause of hospitalization in most patients. Unfortunately, pain in chronic pancreatitis has been very difficult to treat, and the investigators' lack of understanding about the underlying biology has led to various empirical approaches that are often based on purely anatomical grounds, and are generally highly invasive. Significant tissue injury such as that observed in chronic pancreatitis not only triggers nociceptor activation but over time, can also increase the pain in the whole system, a process called sensitization.~Determination of the contribution of peripheral versus central factors to nociceptive sensitization has significant clinical implications in an individual patient. Thus, if pain is caused primarily by signals emanating in the peripheral nerves, then perhaps invasive procedures directed against the pancreas (including pancreatectomy) are justified and can be expected to have a high probability of success. On the other hand, if central sensitization is the dominant pathophysiological factor, then these procedures may cause more harm than good and the patient may be best served using aggressive neuromodulator therapies.~The most direct way to address this question is to interrupt peripheral nerve signaling and determine how much of the pain, if any, is taken away. Unfortunately, there are no satisfactory methods to do this currently. Although celiac or splanchnic nerve blocks have been used for the treatment of pain in chronic pancreatitis, the treatments have had limited success for a variety of reasons, including the fact that the technique may not always be accurate in terms of the site of injection.~The investigators hypothesize that the best method to reliably abolish peripheral nerve signaling is the use of a local anesthetic within the target organ (i.e. pancreas). This can best be done during endoscopic retrograde cholangiopancreatography (ERCP), a technique in which the main pancreatic duct is cannulated with the help of a duodenoscope and contrast material injected. This technique is routinely done to assess pancreatic duct anatomy prior to consideration of a therapeutic intervention such as a stent, stricture dilation, or stone removal/lithotripsy.~Since ERCP is done under deep sedation or general anesthesia, it is critical to select a local anesthetic whose effect persists well after recovery from the procedure; if not, the assessment of the effect of the local anesthetic on pain will be impossible to assess. The investigators have therefore chosen liposomal bupivacaine (Exparel, Pacira Pharmaceuticals), which is an FDA approved product for local infiltration that has a longer duration of action (up to 72 hours) and a slower absorption into the systemic circulation, avoiding high plasma concentrations.

The major clinical features of chronic pancreatitis include glandular (exocrine and endocrine) failure and pain. Pain has remained a major clinical challenge and is present in up to 90% of patients and is the primary cause of hospitalization in most patients. Unfortunately, pain in chronic pancreatitis has been very difficult to treat.~The investigators hypothesize that the best method to reliably abolish peripheral nerve signaling is the use of a local anesthetic within the target organ (i.e. pancreas). This can best be done during endoscopic retrograde cholangiopancreatography (ERCP).~Since ERCP is done under deep sedation or general anesthesia, it is critical to select a local anesthetic whose effect persists well after recovery from the procedure; if not, the assessment of the effect of the local anesthetic on pain will be impossible to assess. The investigators have therefore chosen liposomal bupivacaine (Exparel, Pacira Pharmaceuticals), which is an FDA approved product for local infiltration that has a longer duration of action (up to 72 hours) and a slower absorption into the systemic circulation, avoiding high plasma concentrations.

It is a prospective, double blinded, Randomized Controlled Trial study. Data will be prospectively collected of all injectable acellular amniotic membrane derived allograft knee performed at our institute (1 vs 2 mL).~90 subjects will be enrolled in the study. Subjects will be randomized 1:1:1 in treatment arms.~It compares the dose affect of an amniotic membrane allograft between a 1 mL dose and a 2 mL dose when compared to a placebo of sterile saline in the treatment of osteoarthritis of the knee. This will be offered as a free pain management alternative to patients who meet the inclusion criteria. The results will be determined by validated patient-reported outcome tools (KOOS, VAS, and WOMAC questionnaires) and physical examinations taken before the injection, one month after the injection, three months after the injection, six months after the injection, and one year after the injection. There will be a phone call 24 hours after the injection for every patient participating in the study regarding any potential adverse events.

The purpose of this study is to determine the dose effect of a single injectable acellular amniotic membrane derived allograft for the treatment of knee osteoarthritis and to confirm whether the use of 2 mL of the same amniotic injection offers a statistically significant advantage over the 1 mL injection when compared to a placebo.

The objective of this study is to determine and compare the in vivo kinematics and vibroarthrography (VAG) signals for subjects implanted with Journey II Bi-Cruciate Stabilized (BCS), CR (Cruciate Retaining), and Bi-Cruciate Retaining (XR) TKAs. The Journey II BCS Knee System was designed to resect and replicate both the PCL and ACL, the Journey II CR System retains the posterior cruciate ligament, while the Journey II XR System retains the cruciate and collateral ligaments so they remain intact.

The objective of this study is to determine and compare the in vivo kinematics and vibroarthrography (VAG) signals for subjects implanted with Journey II Bi-Cruciate Stabilized (BCS), CR (Cruciate Retaining), and Bi-Cruciate Retaining (XR) TKAs.

This is a preliminary pilot study to generate data to optimize an insulin dosing algorithm to regulate glucose levels in children with type 1 diabetes. There will be up to two 40-hour test in outpatient settings, in which we will assess an insulin dosing algorithm. The two tests will allow us to compare different tunings in the same patient (this allows easier interpretation of the data). For example, if in a specific participant, the dosing algorithm reduced insulin delivery at night to avoid low blood glucose levesl but led to a rebound increase in glucose levels, then a second visit with a slightly different target range will help answer this question. The objective of this clinical trial is to assess the safety of our algorithm in children with type 1 diabetes in a free-living study.

The objective of this clinical trial is to assess the safety of our insulin dosing algorithm in children with type 1 diabetes in a free-living study.

The demographic data will be collected from all participants including patient's age , BMI , gestational age, personal,present and past obstetric history, with special emphasis on: history of impaired sleep due to insomnia or sleep deprivation due to working on night shifts, history of insomnia during first 20 weeks of pregnancy.Number of night sleep hours and total number of sleep hours during the day will be recorded for each participant. The Insomnia severity index(ISI) a brief self report questionnaire used for assessing the degree of current insomnia will be administered to all participants at the time of their routine antenatal care visits to detect insomnia and its severity if present .It will be applied both in English and in its Arabic translated version. The ISI comprises seven items assessing the type of insomnia problem, satisfaction with the current sleep pattern, affection of the quality of life by the sleep problem, the degree of distress related to insomnia and its affect on daily functioning .Each item is scored on a scale of 0-4 and the total ISI score ranges from 0-28, with higher scores indicating more severe insomnia. A written informed consent will be obtained from each participant before joining the study. The participants will be followed up throughout their 3rd trimester till the time of their delivery. Any drop-out cases will be reported. The pregnant women who didn't suffer insomnia in any of the assessments, nor were sleep deprived due to working on night shifts will comprise the the non impaired sleep group and those suffering clinical insomnia as detected by the insomnia severity index (total score > or equal to 15) in any or all of the assessments will comprise the insomnia group. The 3rd group (sleep deprived group) will be comprised of participants who are only sleep deprived due to working on night shifts and not due to insomnia. Those getting less than 7hours of sleep/day will be considered sleep deprived.~The patients will be assessed during their routine visits with transabdominal ultrasound and Doppler studies for evaluation of fetal growth ,fetal well being ,placenta and exclusion of congenital anomalies, abnormal fetal position or presentation .The gestational age at delivery,mode of delivery,presence of prolonged or painful labour and fetal birth weight will all be recorded for comparison.

This prospective observational study aims at investigating whether insomnia or sleep deprivation during the 3rd trimester of pregnancy can be implicated in the occurrence of adverse maternal or fetal outcome. Data will be collected from all participants with special emphasis on: history of impaired sleep due to insomnia or sleep deprivation due to working on night shifts, history of insomnia during first 20 weeks of pregnancy.Number of night sleep hours and total number of sleep hours during the day will be recorded for each participant. The Insomnia severity index(ISI) a brief self report questionnaire used for assessing the degree of current insomnia will be administered to all participants at the time of their routine antenatal care visits to detect insomnia and its severity if present .The possible relationship between clinical insomnia or sleep deprivation and the occurrence of preterm birth or IUGR will be explored and the association with increased Cesarean delivery rate or painful and/ or prolonged labour.

Allocetra-OTS is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state.~This is a multi-center, randomized, placebo-controlled, dose-finding study comparing the efficacy, safety and tolerability of different dosing regimens of Allocetra-OTS, in patients with sepsis. The study aims to compare the safety and efficacy of different doses and regimens of Allocetra-OTS, as well as the clinical manifestations following Allocetra-OTS treatment, to that of Placebo in the treatment of organ failure in adult sepsis patients.

A Phase 2, Multi-Center, Randomized, Placebo-Controlled, Dose-Finding Study Evaluating Efficacy, Safety and Tolerability of Different Doses and Regimens of Allocetra-OTS for the Treatment of Organ Failure in Adult Sepsis Patients

Experimental: ASC(Autologous Adipose-derived Stem Cells) and Fibringlue, Comparator: Fibringlue, Study type: Interventional, Study design: Randomized

This is a phase III study to evaluate the efficacy and safety of ASC(Autologous Adipose-derived Stem Cells) and Fibringlue or Fibringlue in Patients With Crohn's Fistula.

Pancreatic carcinoma is one of the deadliest types of cancer. In contrast to other cancers, new treatment options have demonstrated only moderate improvements for pancreatic cancer in terms of overall survival. Patients with metastasized disease (stage IV, AJCC) that are treated with chemotherapy in the Netherlands currently present a median overall survival of 6.4 months. Previous research has shown promising results for patients with locally advanced pancreatic cancer (LAPC, stage III, AJCC) with regards to combination treatment with chemotherapy and irreversible electroporation (IRE), a local ablation technique that utilizes electrical pulses to destroy cancerous tissue. In addition to an increase in overall survival, IRE induced a systemic immune response. However, the immune response was not potent enough to generate a lasting anti-tumor effect. Leveraging the body's own immune response by using local and systemic immunotherapy may create a synergistic effect, potentially inducing a durable anti-tumor response. The PANFIRE-III is a prospective randomised phase 1 trial with the primary aim to determine safety of the combination therapies IRE + Nivolumab (arm B) and CpG + IRE + Nivolumab (arm C) in patients with oligo-metastasized pancreatic cancer. The secondary goal is to determine efficacy of the experimental arms (arm B, C) compared to the control arm A (Nivolumab monotherapy). This will be assessed by looking at the overall and progression-free survival as well as the locoregional and systemic immune response. The treatment combination of IRE with immunotherapy has the potential to generate systemic protection by in vivo vaccination against pancreatic cancer cells, hereby inhibiting both local and distant tumor growth.

Irreversible electroporation is a local ablative technique used in the treatment of pancreatic cancer. In addition to its cytoreductive ability, IRE also induces a systemic immune response. However, this immune response is not potent enough to establish durable regression of the tumor. The immune response can be leveraged by combining IRE with immunotherapy. The primary aim of this study is to determine the safety of IRE + Nivolumab (arm B) and IRE + Nivolumab + CpG (arm C). The secondary aim is to assess efficacy of the experimental arms (B, C) and control arm A (Nivolumab monotherapy), based on overall and progression-free survival as well as locoregional and systemic immune modulation.

Scientific rationale Interleukin (IL)-5 is the main cytokine responsible for the activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in patients with severe asthma.~Response to biologic therapies in severe asthma is variable, with patients being either non-responders, responders or super-responders. There is currently no explanation for this broad variation in response. It is important to examine whether these patients have distinct characteristics that could help the treating physician in making the correct diagnosis in clinical practice.~Aim of this clinical study is to evaluate the efficacy of mepolizumab, a humanized IL-5 antagonist monoclonal antibody in patients with late-onset severe eosinophilic asthma with fixed obstruction and to identify the characteristics of non-responders and super-responders under mepolizumab treatment. This study is considered as non-interventional and every procedure included is happening in a clinical routine for the diagnosis and phenotyping of the asthmatic patients.~Several methods are used to investigate airway inflammation: direct measurements (like bronchial biopsies or bronchoalveolar lavages) and indirect methods (like symptom assessment, blood sample analysis and lung function tests). The direct techniques have the advantage of reliably assessing the airway inflammation, but they are invasive and not feasible at large scale because of patient discomfort and the risk incurred. As for the indirect methods, they poorly correlate with the direct assessment of airway inflammation.~In this study, among patients' clinical characteristics spirometry, biomarkers of inflammation (blood eosinophils, FeNO, IgE levels), impulse oscillometry (IOS) and the thickening of basement membrane via bronchoscopy will be evaluated. It is suggested that late-onset severe eosinophilic asthmatic patients with fixed obstruction who do not respond to the usual treatment (ICS/LABA/LAMA) appear with increased smooth muscle mass. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known and may vary with disease severity. In addition, biomarkers of inflammation will also be evaluated before and after 52-week mepolizumab treatment in biological fluids (serum, sputum, sputum supernatant and bronchial samples). Biomarkers of inflammation are very important to identify responders to non-responders.~More specific, IOS has been introduced as an alternative technique to assess lung function with particular application to asthma. This technique is noninvasive, easily performed during tidal breathing and requires only minimal patient cooperation.~Sputum collection is another way to sample cells from the airways and allows the direct assessment of airway inflammation. Furthermore, examples with sputum supernatant include the analysis of mediators and the assessment of the chemotactic activity of the sample for eosinophils. The sputum cells can also be analyzed by flow cytometry which allows, among others, immunophenotyping and sorting cells. Furthermore, sputum cells can be cultured, and their mediator production can be measured in vitro. It is worth noting that in this case, the mediator content is different from what can be found in sputum supernatant. Indeed, mediators in sputum supernatant may be influenced by secretions from airway resident cells and by plasma exudation, contrary to the sputum cell culture model. Finally, immunocytochemistry and in situ hybridization can also be performed using sputum cells.~Although phenotypes, blood eosinophils, and serum IgE levels have been proposed for use as a reference, there is a dissociation between the blood immune-cell level and the airway epithelium immune reaction, as confirmed in previous studies. Airway epithelium immunohistochemistry staining for targeted immune cells has been used to determine various types of airway inflammation; however, this technique is rarely used in a clinical setting. Previous studies have revealed the relative safety of performing bronchoscopy biopsies for patients with severe asthma. Among the sampling techniques used for tissue diagnosis, including nasal biopsies, nasal or bronchial brushing, and bronchoalveolar lavage, bronchoscopy-guided bronchial epithelium sampling provides more accurate information about the epithelial and inflammatory cells in the tissue context. It is thus a powerful tool for selecting the most suitable biologics in difficult clinical conditions.~Besides, asthmatic disease is characterized by a chronic mucosal inflammatory process, which results in irreversible changes of the bronchial wall, known today as bronchial remodeling. Glandular and smooth muscle fibers hyperplasia and/or hypertrophy, goblet cells hyperplasia, and variable thickening of basement membrane (BM) present under the respiratory epithelium are part of these morphological changes. the changes generated at the epithelium-connective interface account for an adaptive response to inflammatory stress and sporadic bronchoconstriction. However, current data on BM reactivity in asthmatic patient are still incomplete for an accurate assessment of its involvement in pathogenesis and specifically in bronchial wall remodeling, mainly as collagen deposits in lamina reticularis are not correlated to the degree of disease severity.~Moreover, it is increasingly evident that severe asthma is not a single disease, as evidenced by the variety of clinical presentations, physiologic characteristics, and outcomes seen in patients with asthma. To better understand this heterogeneity, the concept of asthma phenotyping and endotyping has emerged. Phenotyping integrates both biological and clinical features, from molecular, cellular, morphologic, and functional to patient-oriented characteristics with the goal to improve therapy. Ultimately, these phenotypes evolve into asthma endotypes, which combine clinical characteristics with identifiable mechanistic pathways. Biomarkers, defined as characteristics that can be objectively measured and serve as an indicator of underlying biological processes or pathogenesis, are crucial in defining phenotypes and endotypes. In asthma, genetic polymorphisms, measures of airway physiology, and levels of inflammatory mediators in urine, blood, sputum, tissue, exhaled gas, and breath condensate have all been studied as potential markers to improve and objectify asthma diagnosis and management. Developing such tools will allow us to phenotype and endotype the various clinical patterns described in asthma, with the ultimate goal of tailoring therapy based on a specific biomarker profile. Biomarkers can then be used to help better understand the pharmacologic response to an intervention and adjust therapy accordingly.~Biomarkers have been critical for studies of disease pathogenesis and the development of new therapies in severe asthma. In particular, biomarkers of type 2 inflammation have proven valuable for endotyping and targeting new biological agents. Because of these successes in understanding and marking type 2 inflammation, lack of knowledge regarding non-type 2 inflammatory mechanisms in asthma will soon be the major obstacle to the development of new treatments and management strategies in severe asthma. Other potential biomarkers include innate lymphoid cells, IL-33 or thymic stromal lymphopoietin.~Recent publications confirmed crucial regulatory role of miRNAs in the pathomechanism of asthma. Some single miRNAs or their sets hold the promise for their use as asthma biomarkers facilitating diagnosis or prediction of treatment outcomes. They are also possible target of future therapies. The studies in this field are lacking though. Recently it has been shown that most of the involved miRNAs increase secretion of Th2 cytokines, decrease secretion of Th1 cytokines, promote differentiation of T cells towards Th2 or play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. The profiles of miRNAs correlate with clinical characteristics, including lung function, phenotype and severity of asthma.~Most industry sponsored biologic clinical trials have effectively used the above approach by selecting study subjects that resemble the severe asthma clinical phenotypes of SARP (high-intensity controller medication regimens, frequent exacerbations, and low lung function), but then require an elevated biomarker (in blood, exhaled gas, or sputum) that should identify patients most likely to be responders to a specific immunomodulator within those clinical phenotypes. The biologics in recently published clinical trials target type 2 inflammatory pathways and restrict participation to subjects with elevated type 2 biomarkers (blood or sputum eosinophils or FeNO). Post hoc responder analyses to group biomarkers to better understand which patients have the greatest benefit from a biologic immunomodulator will lead to an understanding that concurrent elevations in more than 1 type 2 inflammatory biomarker may further identify high responder patients.~Hypothesis includes the efficacy of mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction and relation to clinical and inflammatory biomarkers.~Research questions Is there any improvement in exacerbation rate in late-onset severe eosinophilic asthmatic patients under mepolizumab treatment during their 1st year of treatment and what are the characteristics of non-responders and super-responders? Is there any improvement in smooth muscle cells remodeling? Are there any biomarkers to predict response to mepolizumab treatment in late-onset severe eosinophilic asthmatic patients? Is there any improvement in respiratory parameters? Is there any improvement in asthma control and patients' quality of life? Objectives~The primary objectives of this study are:~To demonstrate the effect of mepolizumab treatment in exacerbation rate in late-onset severe eosinophilic asthmatic patients with fixed obstruction.~To identify characteristics of non-responders and super-responders.~Stydy's extension to identify any improvement in airway remodeling after 156 months of treatment~The key secondary objectives of this study are:~Any improvement in remodeling (thickening of bronchial smooth muscle cells).~Any possible biomarkers of response.~Any improvement in respiratory parameters in asthma control and in patients' quality of life during mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction.~Study design and Methods Patients will be collected from the outpatient clinics of bronchial asthma from each site (8 in number) which cover the population of Greece. All these Clinics are included to reinforce the recruitment as well as to include bronchoscopist experts with international impact. Due to the current situation concerning Covid-19 pandemic, the investigators assume that this clinical study does not interfere with the workload in our Clinics.~Overall, this is a prospective multicenter study including eight Pulmonary Clinics. Five Pulmonary University Clinics, two of National Health System and one Army General Hospital.~The study will include a screening period of up to 2 weeks to assess eligibility and obtain written informed consent, a mepolizumab treatment period of 52 weeks, once every 4 weeks, including follow up visits every 3 months during treatment.~The extension of the protocol includes a treatment period of 156 weeks of treatment.~The study population will consist of 45 patients with late-onset severe eosinophilic asthma and fixed obstruction receiving mepolizumab aged 20 and above.~Study participation, assessment and follow up:~Screening: Investigators will screen selected subjects to the participated clinics (Severe Asthma outpatient clinics). Subjects will come in to sign consent. Clinical assessment and procedures and structural interviews will be performed during screening. Subjects that are eligible/able to complete the screening Visit may do so, on the same day, and if necessary, they will complete their baseline assessment within 2 weeks. Subjects with an ongoing asthma exacerbation should have their screening and treatment initiation visit delayed until the investigator considers the subject has returned to their baseline asthma status. If the 2-week screening period has elapsed then the subject should be considered a screening failure. Subjects will remain on their current maintenance therapy throughout screening periods. Eligibility of the patients will be based on the criteria listed in the next sections.~Asthma exacerbation history for the last 12 months will be reported at screening visit. Also, exacerbations will be evaluated at each visit as reported.~Vital signs will be performed at screening visit, at baseline and every 3 months. Measurements will include systolic and diastolic blood pressure, pulse rate and body temperature.~Height in centimeters (cm) and body weight in kilograms (kg) will be measured at screening visits. Body Mass Index (BMI) will be calculated as the weight in kg divided by the height in meters squared~Laboratory evaluation (Hematology, Blood chemistry, Urinalysis):~Venous blood and urine will be collected at baseline. Hematology: Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential, and platelet will be measured in the laboratory of each site's hospital. Basic clinical chemistry and urinalysis will be evaluated. Collection of urine for female subjects will also evaluate pregnancy.~IgE levels will be evaluated at screening visit using immunoCAP tests and will be reported as IU/mL.~The following Questionnaires will be administered: 1) the Asthma Control Questionnaire (ACQ-5) and Asthma Control Test (ACT) to assess current asthma control; 2) the Asthma Quality of Life Questionnaire (AQLQ+12) to assess quality of life and psychological morbidity. To further asses sleeping quality 1) Athens Insomnia Scale (AIS), 2) Epworth Sleepiness Scale (ESS), 3) St. George's Respiratory Questionnaire (SGRQ) and 4) WHO (Five) Well-Being Index (WHO-5), 5) Fatigue Severity Scale (FSS).~Exhaled nitric oxide (NO) will be measured at baseline and every 3 months according to the American Thoracic Society Guidelines and as specified by the manufacturer. FeNO levels will be reported as parts per billion. Measurements will be made before spirometry is performed.~Venous blood samples will be retrieved between 8 to 10 am, at baseline and every 3 months during the 52-week period with mepolizumab treatment. Absolute blood eosinophil count will be reported as cells/μl.~Spirometry: Spirometry A will be conducted, using the site's own equipment at the visits (baseline and every 3 months). All clinic visits must occur in the morning. During the treatment period the spirometry will meet the current ATS/ERS guidelines and the spirometer must produce a printout of all data generated, which should be stored in the subject's notes. The spirometer will be calibrated in accordance with the manufacturer's instructions. Spirometry must be performed at the same time (±1 hour) of the Visit 0 spirometry. Subjects should try to withhold short-acting beta-2-agonists (SABAs) for ≥4 hours and LABAs for ≥15 hours prior to clinic visit, if possible (GINA 2019). Assessments to be recorded will include FEV1, FVC, FEV1/FVC%, PEF and FEF25-75. Post-bronchodilator measurements will be taken at every visit, using 200-400mcg albuterol or equivalent.~Spirometry B will be conducted, using the site's own equipment at the visits (baseline, after 6 months and after treatment at 52 weeks timepoint). Spirometry B includes diffusion, pulmonary volumes and capacities.~Impulse oscillometry (optional):~Impulse Osillometry (IOS) will be conducted at baseline and after 52 weeks of treatment. IOS includes resistance at 5 Hz-resistance at 20 Hz (R5-R20), a measure reflecting respiratory resistance of small to midsized conductive and peripheral airways, AX, a measure reflecting distensibility of the peripheral lungs (namely the parenchyma and small peripheral airways), and the respiratory system reactance (X5), a measure reflecting inertance and elasticity or capacitance (including small peripheral airways).~Therapy with biologics:~Upon completion of the screening visits the participant may initiate treatment with biologic therapy (mepolizumab) within a month. During therapy subjects will be under the care of the pulmonologist who had referred them to the research group for taking part into the study. These pulmonologists will be termed as 'associate pulmonologists. Treatment will be provided as per product manufacturer instructions.~Associate pulmonologists providing biologic treatment during the study will require to sign an agreement to conduct the study in compliance with the protocol, to acknowledge that he/she is responsible for medical conduct and for study conduct, and to ensure that the associate (and their colleagues and employees) assisting in the conduct of the study are informed about their obligations. Mechanisms will be in place to ensure that associate staff receives the appropriate information and support by the research group throughout the study.~Follow up during biologic therapy: At initiation and at every visit for biologic therapy administration collection of information will be performed by the associate pulmonologist, and with support by the research group if requested by the associate pulmonologist e.g., researchers via telephone or face-to-face contact will interview the patient. Furthermore, compliance will be recorded form the physician based on patient's oral confirmation. Date form of drug administration will be recorded at every visit, as well as immediate and delayed adverse effects.~Safety monitoring:~Recorded adverse events (AEs) will be monitored and collated as required in study reports. An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study entry. Medical conditions/diseases present before starting study drug are only considered adverse events if they worsen after starting study drug. Abnormal laboratory values or test results constitute adverse events only if they induce clinical signs or symptoms, are considered clinically significant, or require therapy. Also, adverse events related to Covid-19 are included. If a partner pulmonologist or research staff becomes aware of an AE associated with a product, it can be reported to the manufacturer according to their local standard practice for spontaneous AE reporting. A copy of the report should also be sent to the study coordinator. Serious adverse events (SAE) will be reported in the eCRF pages and within 24 hours all the investigators will have the responsibility to inform the Central Committee in Thessaloniki. Then the Central Committee will inform the scientific board and the Greek Medical Agency. Also, medical and scientific judgment will be exercised by the principal investigator of each center with the Central Committee, in deciding whether the subject should stop the treatment or not.~Pregnancy report:~Initially, female patients at screening will have to do a pregnancy test. During treatment, if a female subject reports a pregnancy to us, she will be asked to withdraw from the study (to prevent bias) Then, she will be asked if she would like to keep getting the treatment outside of this protocol and be monitored at each center's outpatient clinic.~Pre-screening and Screening Failures:~Subjects will be assigned a study number at the time of signing the consent. Subjects who signed but do not progress to the screening visits assessment will be deemed a pre-screen failure. No data will be captured in the database for these subjects.~Subjects that complete at least one of the two screening visits, but do not initiate biologic therapy will be designated as screening failures. Information to be collected for pre-screening and screening failures will be detailed in the database completion.~Withdrawal Visit:~If a participant decides to withdraw from the study during follow-up (for any reason other than loss to follow up), they may be asked to attend a withdrawal visit (if deemed necessary by investigator and subject to consent). During the visit, the participant may be asked questions about their current conditions as part of clinical information collection such as: asthma and nasal symptoms, exacerbations and the progression of treatment being received.~Blood samples' collection and processing:~Blood samples will be collected at baseline visit, at 6 months and after treatment completion. After collecting the blood samples, they will be left undisturbed for about half an hour for complete clot formation. The sample will then be centrifuged to separate the serum from the clot. After centrifugation the serum will be stored at -20° C in eppendorf tubes till the analysis was done. Blood phenotyping will also be evaluated by flow cytometry.~Induced sputum (optional):~Induced sputum will be performed at baseline before treatment initiation and after completion of treatment according to the ERS Task Force report where a detailed expert consensus-based recommendation for induced sputum processing is suggested.~At the visits, sputum induction will be performed after the routine spirometric assessments have been completed.~The induced sputum will be processed within two hours of the end of the induction procedure at the research site. Sputum cells and cell suspension supernatant will be stored at -80ºC for analysis. After collecting the induced sputum, the supernatant of the sample will be stored at -20° C in eppendorf tubes till the analysis was done. Following these procedures, laboratory evaluation of the sputum is next according to guidelines.~Bronchoscopy, bronchial biopsies and washing samples' collection and processing (optional): At the visits, endoscopy with bronchial biopsies, bronchial washing sample (Visit 0b) will be performed upon patient's written consent. In specific, a separate inform consent will be included to be signed from each patient. Bronchoscopy will be performed at two time-points (baseline before treatment initiation and after the completion of treatment). Flexible bronchoscopy and diagnostic techniques were performed under monitored anesthesia care as recommended by the American Thoracic Society and the British Thoracic Society.~Tissue samples will be fixed in inflation or immersion using formaldehyde or glutaraldehyde and embedded in paraffin. Airways will be systematically sampled or obtained during diagnostic dissection at the discretion of the pathologist. Consecutive sections of 0.5, 5 and 30 μm thickness were cut from each block and stained using the Masson's trichrome technique, haematoxylin and eosin, and haematoxylin, respectively. Immunohistochemical staining will be done done with the following mAbs: anti-mast cell tryptase clone AA1 (Dako UK), anti-alpha smooth muscle actin clone 1A4 (Dako UK), anti-eosinophil major basic protein clone BMK-13 (Monosan, Netherlands), anti-neutrophil elastase clone NP57 (Dako UK), and anti-endothelium clone EN4 (Monosan, Netherlands) or appropriate isotype controls were used.~The endobronchial biopsies will be assessed by a single observer blinded to the clinical characteristics (ZEN 2012 image analysis software for light microscopy, Carl Zeiss AG, Germany) and will be expressed as the mean of measurements undertaken from a minimum of two sections either from independent biopsies or as non-contiguous tissue sections at least 20μm apart from the same biopsy. Epithelial integrity will be assessed by measuring the lengths of intact and denuded epithelium. These will be expressed as percentage of all the reticular basement membrane (RBM) length. Vascularity will be measured using the Chalkley count, a surrogate of both vessel density and vascular area. A Chalkley eyepiece graticule (NG52 Chalkley Point Array, Pyser-SGI Ltd, UK) will be used at x200 to measure Chalkley counts in four non-overlapping vascular hotspots (6). Airway smooth muscle content will be determined as the proportion of the total area. Inflammatory cells were expressed as the number of nucleated cells/area of lamina propria.~Bronchial washing samples will be immediately transported to the laboratory, to be stored at -80 degrees. Examination of bronchial washing fluids will be performed at a later stage to determine several biomarkers.~Analysis of biomarkers of inflammation with Flow Cytometry Analysis (FACS) or ELIZA:~Biomarkers included before and after treatment with mepolizumab in two or three timepoints, (at baseline, at 6 months treatment and after treatment completion visit): lymphocyte subsets, Th2/Th17 cytokines, chemokines, microRNAs expression to be quantitated by flow cytometry or ELISA) in biological fluids (blood, serum, bronchial washing, sputum and sputum supernatant).~Panel kits and appropriate antibodies will be tested by Flow Cytometer Analysis using a BD FACS Calibur system (BD Biosciences, San Jose, CA), according to the manufacturer's recommendations and instructions.~ELISA (enzyme-linked immunosorbent assay) is a plate-based assay technique designed for detecting and quantifying substances such as peptides, proteins, antibodies and hormones. ELISA kits will be analyzed using VICTOR X3 spectrophotometer according to the manufacturer's recommendations and instructions.~Allergy testing (If applicable) The patients' atopic status will be evaluated (if not available) at screening visit by the skin prick test (SPT) to a standard panel of aeroallergens for detecting total IgE antibodies against various common inhalant allergens.~Database An electronic data collection platform will be the method used at baseline every 3 months until 1 year follow up for this database. During treatment visits paper forms/questionnaires will be completed by the associate pulmonologist. Each site will entry specific data in an electronic database. Each patient is uniquely identified by a Subject number which is composed by the site number assigned by the responsible monitoring site and a sequential number assigned by the investigator. Upon signing the informed consent form, the patient is assigned the next sequential number by the investigator. The site must contact the central research personnel and provide the requested identifying information for the patient as registered into the electronic database. The treatment visit forms will also be sent to the central research personnel. The authorized study personnel will be responsible for data collection, editing, and also protecting the data being collected at their own site and the database is backed up on a daily basis. Quality review/control will be the joint responsibility of all individuals involved and the central research personnel [data custodian].~Sample size calculation G power analysis Sample size is calculated using the G*Power software (Die Heinrich-Heine-Universität Düsseldorf, Germany). The difference in annual exacerbation rate of the patients with late onset severe eosinophilic asthmatics before and after Mepolizumab treatment with is the primary endpoint of the study. In the DREAM study (one of the only two studies that has reported results similar to our primary endpoint so far) it was reported that the annual exacerbation rate of patients with severe Asthma declined from 3.6 to 1.33 after the initiation of treatment with Mepolizumab. Using this data and a two-sided test, with a power at 0.95 and a level of statistical significance at 0.05, the investigators calculated an effect size of 0.556, which indicated a total sample size of 45 participants.~Statistical Plan Analysis Statistical analysis will be performed using the SPSS (version 21.0 IBM SPSS statistical software, Armonk, NY, USA). Categorical variables will be stated as numbers (n) and percentages (%), continuous variables as mean ± SD if normally distributed, or median and interquartile ranges if otherwise. Where necessary variables without a normal distribution will be transformed. P < 0.05 was accepted as statistically significant. Shapiro-Wilk test will be performed in order to separate parametric from non-parametric variables. Paired-Samples T Test for parametric or Wilcoxon Signed Ranks test for non-parametric variables will be used to detect differences in the variables measured before and after Mepolizumab treatment.~There is no comparator arm as every patient is control to himself. There are baseline characteristics (clinical and laboratory biomarkers) that are going to be measured at baseline, every 3 months and after 52-week treatment completion. Study endpoints include the analysis of all those biomarkers as the identification of the characteristics of non-responders and super-responders. Also, secondary endpoints include the evaluation of the biomarkers mentioned in the methods as assessments. Statistical analysis will be performed initially with the number of patients that have completed the 52-week period of treatment. Secondly, patients that have not completed the 52-week treatment will be analyzed separately and finally these two groups are going to be compared to each other.~More specifically, with univariate analysis (two-sided independent sample tests) the investigators will test for associations/correlations between all baseline outcomes compared with the ones after mepolizumab treatments (every 3 months until 1 year of treatment): biomarkers in sputum and in blood, clinical outcomes. Similarly, univariate associations between outcomes and personal/demographic characteristics will be tested for identifying potential confounders. Significant associations will be then tested with adjusted regression models. Associations/correlations will be evaluated separately at baseline clinical characteristics and every 3 months follow up during treatment as well as at baseline and after 1 year of mepolizumab treatment. Besides, subgrouping analysis will be performed for each biomarker for the identification of biomarker level to treatment response.~Paired-Samples T Test for parametric or Wilcoxon Signed Ranks test for non-parametric variables will be used to detect differences in the variables measured before and after Mepolizumab treatment. In specific, levels of biomarkers at baseline will be compared to levels after 1-year of mepolizumab treatment.~Overall response to treatment in one year (from baseline to 1-year post treatment initiation) for each outcome will be measured with paired test of dependent samples (parametric and non-parametric paired tests) in each patient. Then response to treatment will be defined as the change (absolute and % change) of the outcome in one year. The investigators will assess predictors influencing response to treatment (change) such as biomarkers by using multiple regression models for each clinicopathological outcome. For outcomes with more than 2 observations per subject during the study period the investigators will use mixed models using the repeated measurements of the outcome. All tests will be 2-sided with a statistical significance level at 5%.

Interleukin (IL)-5 is the main cytokine responsible for the activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in patients with severe asthma.~Response to biologic therapies in severe asthma is variable, with patients being either non-responders, responders or super-responders. There is currently no explanation for this broad variation in response. It is important to examine whether these patients have distinct characteristics that could help the treating physician in making the correct diagnosis in clinical practice.~Aim of this clinical study is to evaluate the efficacy of mepolizumab, a humanized IL-5 antagonist monoclonal antibody in patients with late-onset severe eosinophilic asthma with fixed obstruction and to identify the characteristics of non-responders and super-responders under mepolizumab treatment. This study is considered as non-interventional and every procedure included is happening in a clinical routine for the diagnosis and phenotyping of the asthmatic patients.~Hypothesis includes the efficacy of mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction and relation to clinical and inflammatory biomarkers.~Patients will be collected from the outpatient clinics of bronchial asthma from each site included (8 in number) which cover the whole population of Greece.~Overall, this is a prospective multicenter study including eight Pulmonary Clinics. Five Pulmonary University Clinics, two of National Health System and one Army General Hospital in Thessaloniki. The study will include a screening period of up to 2 weeks to assess eligibility and obtain written informed consent, a mepolizumab treatment period of 52 weeks, once every 4 weeks, including follow up visits every 3 months during treatment. The study population will consist of 45 patients with late-onset severe eosinophilic asthma and fixed obstruction receiving mepolizumab, aged 20 and above.

Object and source: Patients diagnosed with DKD who meet the inclusion criteria are enrolled into the study.~Observation index: At baseline and every medical visit, therapeutic relevant information was collected. Data mainly include demographic characteristics(age, gender, place of residence, marriage, education degree), lifestyles(smoking, drinking, exercise), clinical characteristics(body mass index, blood pressure, duration , history of CVD, complications, nutrition situation), laboratory indexes (serum creatinine, blood urea nitrogen, glycosylated hemoglobin, urinary albumin to creatinine ratio, 24-hour urinary albumin, 24-hour urine urea nitrogen, etc.).~Quality assurance plan: The present study should be performed according to the principles of the Declaration of Helsinki and has been approved by the Ethics Committee of Guangdong Provincial People's Hospital.~Plan for missing data: When the participants drop out, the researcher should contact the participants by phone, email, text message, letter etc. and ask the reason, making record as full as possible.~Statistical analysis plan: Data are presented as mean±SD for continuous variables and as a number(percentage) for categorical variables. According to sex and CKD stage , patients are divided into four groups,then evaluate the prognostic value of mean sUCR and ΔsUCR (fluctuation of sUCR over time, meaning monthly rate of change) in the progression of DKD. The relationship between baseline characteristics among the four groups was compared by using one-way analysis of variance test, Kruskal-Wallis test or Chi-squared test where appropriate. Survival rates are estimated using Kaplan-Meier analysis, and the significance of differences was analyzed using the log-rank test. Cox proportional hazard regression analysis is used to assess the association between the clinical outcomes and mean sUCR and ΔsUCR. In multivariate analysis, we enter variables using a P value of <0.10 as the selection criterion or considered clinically significant. Hazard ratios (HRs) are presented with 95% CIs. All statistical analysis was performed with the use of SPSS (version 19.0, SPSS, Chicago, USA) and Prism 7.0 (GraphPad Software, San Diego, CA, USA). A two-tailed P value <0.05 was considered to be statistically significant.

Research Objective: To evaluate the prognostic value of serum urea nitrogen to creatinine ratio (sUCR) in the progression of DKD.~Research Design: This study was designed as a multicenter, retrospective cohort study. According to sex and CKD stage , patients are divided into four groups,then evaluate the prognostic value of mean sUCR and ΔsUCR (fluctuation of sUCR over time, meaning monthly rate of change) in the progression of DKD.

The purpose of this study is to determine the effect of intermittent, nearly vertical, patient positioning in a specialized upright bed, on outcomes of mechanically ventilated patients with acute respiratory distress syndrome (ARDS) who are in the ICU. This study is a prospective, non-blinded, feasibility, randomized study of ARDS patients, who will be randomized into two treatment groups. One treatment arm will deliver scheduled sessions of upright bed positioning (study intervention), while the other treatment arm receives routine bed position care (care provided exclusively with the bed in the supine position). ICU Practitioners know that positional changes improve clinical outcomes when turning patients from supine to prone (back to belly); however, other positional changes including upright positioning are far less studied. It is well known that in ARDS patients who become proned, an improvement in aeration occurs in the dorsal lung regions (prone positioning has been shown to reduce ARDS mortality). Thus the investigators predict that in this study, the upright positioning holds the potential to further recruit collapsed lung areas. Augmentation of aerated lung while in the upright position is expected to increase the highest value measured per ventilator day of the respiratory system compliance in the upright bed position arm, in a greater fashion than the highest value measured per ventilator day of daily total respiratory system compliance for the usual care arm.

The purpose of this study is to determine the effect of intermittent, nearly vertical, patient positioning in a specialized upright bed, on outcomes of mechanically ventilated patients with acute respiratory distress syndrome (ARDS) who are in the ICU.

To evaluate the safety and immunogenicity of Hepatitis A (Live) Vaccine, Freeze-dried produced by Changchhun Institute of Biological Products Co., Ltd, we design this randomized, parallel controlled study. 450 subjects are divided into 3 groups, including 1 experimental group and 2 control groups (Research Group 1, 2, and 3), each group assigned 150 subjects respectively.~All subjects are aged 18-24 months old.~150 subjects from Research Group 1 will be administrated with one dose of Hepatitis A (Live) Vaccine, Freeze-dried produced by Changchhun Institute of Biological Products Co., Ltd. Blood samples are collected before vaccination and one month (30 days) later.~150 subjects from Research Group 2 will be administrated with one dose of Hepatitis A（Live）Vaccine，Freeze-dried produced by Zhejiang Pukang Biotechnology Co., Ltd. Blood samples are collected before vaccination and one month (30 days) later.~150 subjects from Research Group 3 will be administrated with one dose of Hepatitis A (Live) Vaccine, Freeze-dried produced by Institute of Medical Biology, Chinese Academy of Medical Sciences. Blood samples are collected before vaccination and one month (30 days) later.~To evaluate the immunogenicity, we will detect and compare the seroconversion rates, and antibody geometric mean concentrations. The safety of all groups will be monitored as well.

Subjects will be recruited and divided into 3 groups:~Hepatitis A（Live）Vaccine，Freeze-dried produced by Changchun Institute of Biological Products Co., Ltd~Hepatitis A（Live）Vaccine，Freeze-dried produced by Zhejiang Pukang Biotechnology Co., Ltd., and~Hepatitis A（Live）Vaccine，Freeze-dried produced by Institute of Medical Biology, Chinese Academy of Medical Sciences.~After immunization, the immunogenicity and safety of three different manufacturers will be compared and the data will be analyzed.

The aim of this study is to investigate the use of benralizumab as treatment for patients with chronic spontaneous urticaria (CSU) who are symptomatic despite the use of antihistamines. It is proposed that benralizumab will deplete eosinophils and basophils from affected skin, improve symptoms of CSU, and improve CSU-related quality of life. This Phase 2b study is designed to evaluate induction and maintenance dosing regimens.

The purpose of this study is to investigate the use of benralizumab is effective in the treatment of chronic spontaneous urticaria (CSU) who are symptomatic despite the use of antihistamines.

Bullous pemphigoid (BP) is a rare disease mainly affecting the elderly. BP is associated with significant morbidity and increased mortality secondary to increased risk of secondary infections, comorbid conditions, and serious side effects from high-dose steroids and immunosuppressants. The aim of this study is to investigate the use of benralizumab as a treatment for patients symptomatic with Bullous Pemphigoid (BP).

The purpose of this study is to investigate the use of benralizumab is effective in the treatment of patients symptomatic Bullous Pemphigoid (BP).

Patients with de Novo metastatic prostate cancer with limited disease spread has been shown to gain benefit from local radiotherapy to the prostate. The internationally accepted fractionation schedule is 3 Gy (Gray) x 19-20 over a course of 4 weeks.~There is continous evidence for even more hypo-fractionated radiotherapy with higher fractionation doses. We will test if the schedule of 6.1Gy x 6 compares to standard of 3 Gy x 19 with regard to patient reported side-effects.

de Novo metastatic prostate cancer with limited metastatic spread benefits from local radiotherapy to the prostate. Two different fractionation schedules will be tested.