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This study is an open, multicenter, Phase Ib/II clinical trial evaluating chimeric antigen receptor-modified autologous T cells targeting Claudin18.2 (CLDN18.2) (CT041 autologous CAR T) in subjects with CLDN18.2 expression-positive, advanced gastric/esophagogastric conjugate adenocarcinoma that has failed at least 2 prior lines therapy and advanced pancreatic cancer that has failed at least 1 prior line therapy. The purpose is to evaluate the efficacy, safety and pharmacokinetics There are two stages in the study. Phase Ib stage is dose escalation and dose expansion study, and Phase II stage is to verify the efficacy and safety of CT041 treatment.

An open, multicenter, phase Ib/II study to evaluate the efficacy, safety and pharmacokinetics of CT041 autologous CAR T-cell injection in patients with advanced gastric/ gastroesophageal junction adenocarcinoma and pancreatic cancer

Autosomal dominant hypocalcemia Type 1 is a rare familial genetic form of hypoparathyroidism. Autosomal Dominant Hypocalcemia (ADH) Type 1 is typically passed down from affected parents to their children.~This is a Phase 2b open label, dose finding study to evaluate the safety and tolerability of CLTX-305 (encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1 as well as the effects of CLTX-305 (encaleret) on blood calcium concentration.~The estimated duration of this study is 41 months. This study plans to evaluate multiple doses of the investigational drug CLTX-305 (encaleret), in addition to safety and efficacy. CLTX-305 is administered orally.~The study is divided into 3 Periods followed by a Long-Term Extension (LTE):~Periods 1: Up to 8 study participants will be admitted to the NIH Clinical Center for 7 days, where they will be administered different doses of CLTX-305 (encaleret) for up to 5 days.~Period 2: Participants from Period 1, and up to 10 new study participants will be admitted to the NIH Clinical Center for 7 days, where they will be administered different doses of CLTX-305 (encaleret) for up to 5 days.~Period 3: 24 weeks during which eligible study participants who completed Period 2 will take CLTX-305 (encaleret) at home.~LTE: Up to 25 months during which eligible study participants who completed Period 3 will take CLTX-305 (encaleret) at home.~Study participants may:~Participate in Period 1~Participate in Period 2~Participate in both Period 1 and Period 2~Participate in Period 3 after completing Period 2~Participate in LTE after completing Period 3

A Phase 2b open label, dose finding study to evaluate the Safety, Tolerability and Efficacy of CLTX-305 (encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1

The study aim to evaluate:~characteristics of pediatric cancer patients admitted to Italian PICUs~risk factors of PICU admission, neurological outcome and mortality.~Inclusion criteria: age <= 18 years, informed consent. Exclusion criteria: informed consent not obtained. After a retrospective analysis (2019-2020), investigators will perform a prospective study over 12 months (March 2021 - February 2021) gathering data from 15-20 Italian PICUs. Each Center can decide whether to participate only in the prospective phase. Data will be recorded in an electronic data collection form in Red Cap.~The following variables will be collected:~Demographic variables: age, sex, ethnicity;~TIP pre-admission clinical variables and at the time of admission: basic diagnosis, comorbidity, Hemopoietic Stem Cell Transplantation (TCSE) number and type, treatment phase, HLA matching, Graft Versus Host (GVH) and grade, veno-occlusive disease, Venous Occlusive Disease~Variables upon entering TIP: PIM3, POPC score, organ failure cause and staging, high intensity treatments, high flow oxygen therapy, dialysis, inotropes or other, fluid overload, immunodeficiency~Clinical variables during hospitalization: organ failure cause and staging, ventilation, modality, presence of pARDS and severity, need for inotropic support, sepsis and severity score (SOFA), inotropes (VIS score), arrest event cardiac, need for HFOV, Extra-Corporeal Membrane Oxygenator, Nitric Oxide, dialysis, Intracranial Pressure monitoring, drugs used for sedation, development of withdrawal syndrome, development of delirium.~Considering the participation of 15-20 centers involving 20 patients in a year, the expected number is 600 patients considering the retrospective phase (optional, therefore some Centers may not contribute) and the prospective phase.~Study sites will also take part to a survey designed to collect data in order to describe Italian PICUs involved in providing care to cancer patients.

The study will describe characteristics of pediatric cancer patients admitted to Italian PICUs and will analyze risk factors of PICU admission, neurological outcome, and mortality. After a retrospective analysis (2019-2020), investigators will perform a prospective study over 12 months gathering data from 15-20 Italian PICUs.

On 16 March 2020, an instruction to postpone non-urgent consultations was given to doctors. Thus, the non-essential and non-urgent follow-up consultations of patients living with HIV were postponed or transformed into teleconsultation or exchanges of e-mails between practitioners and patients. This change in care can have an impact on follow-up and access to treatment for PVVIH. In addition, the epidemic itself may have consequences: PVVIH may be at greater risk because of their immunosuppression and associated co-morbidities.

The non-essential and non-urgent follow-up consultations of patients living with HIV were postponed or transformed into teleconsultation or exchanges of e-mails between practitioners and patients during COVID-19 epidemic. This change in care can have an impact on follow-up and access to treatment for PVVIH.

Most (80-90%) COVID-19 positive patients are asked to self-isolate at home because they do not qualify for home care or inpatient admission. Alternatives to in-person care are urgently needed to: (1) manage an unpredictable clinical course; (2) identify and intercept patients rapidly deteriorating at home, (3) prevent viral spread during in-person visits; and (4) triage symptoms to minimize surges to emergency departments (EDs). In addition, fingertip pulse oximeters (pulse oximetry) have been proposed to improve in-home early detection of respiratory deteriorations but are untested and the operational infrastructure to support large-scale monitoring is limited. While telemedicine has been widely adopted during the pandemic as an alternative to conventional outpatient care, worse COVID-19 outcomes observed among Black and Latino patients may be due, in part, to worse telemedicine access for these socially and medically disadvantaged groups.~To improve in-home monitoring and health care access for patients with suspected or confirmed COVID-19, the health innovation team at University of Pennsylvania Health System (UPHS) developed COVID Watch, a free of charge, 24/7, automated, text message-based, home monitoring program across UPHS' large geographic catchment area. This study will answer the question, How does the addition of pulse oximetry affect clinical outcomes for COVID-19 patients?~COVID Watch was first implemented on March 24, 2020 and has enrolled 3,628 patients through May 21, 2020 of which 1,295 were COVID-19 positive. Understanding the effect of COVID Watch with and without pulse oximetry on Black and Latino patients is important because communities of color have had disproportionately higher rates of COVID-19 morbidity and mortality nationally, and locally in Pennsylvania, ranking 5th total deaths, and New Jersey, ranking 2nd. Symptom monitoring apps and programs are commercially available. However, COVID Watch is uniquely embedded into its host healthcare system, UPHS. Patients are enrolled using the electronic medical record (EMR), escalations are addressed by UPHS nurses, and they are referred to UPHS-based telemedicine, primary care, and social services when appropriate. COVID Watch is a scalable operational platform for monitoring patients with home pulse oximetry readings. Whether remote monitoring with or without pulse oximetry helps COVID-19 patients stay safe at home is an urgent, patient-centered question. Finally, with COVID-19 surges projected in late 2020, health systems will need to be prepared with evidence-based strategies for managing more COVID-19 patients at home.~COVID Watch (https://covidwatch.waytohealth.org/) is powered by UPHS' NIH-funded research and operational texting platform (www.waytohealth.org), integrated with UPHS' EMR. Since hypoxemia is the primary driver of admission and fatality among COVID-19 patients, the investigators focused the algorithm on shortness of breath, our closest approximation for concerning hypoxemia. Given the rapid and unpredictable decompensation of COVID-19 patients, patients receive clinical support 24 hours/day, 7 days/week. COVID Watch sends twice-daily, scheduled text messages to assess patients for shortness of breath using an algorithm to determine whether patients need an urgent escalation to a team of dedicated nurses within 1 hour. These nurses are supported by an on-call team of clinicians who can conduct urgent phone or video assessments. At each level patients' clinical needs are either managed with self-care advice, prescriptions, or a referral to the ED. The majority of COVID Watch patients (83.7%) have been enrolled by outpatient providers conducting telephone and video visits; 8.7% and 7.6% have been enrolled at ED and inpatient discharge, respectively. The program is available at all six of UPHS's hospitals and EDs, and all 530 affiliated ambulatory settings using the EMR. Any clinical staff member (e.g., RN, physician, medical assistants) logged on to the EMR is able to enroll patients. Patients can also trigger the algorithmic assessment independent of the scheduled messages. Patients only continue the intervention if they are agreeable (opt-out) and can stop anytime. Patients are scheduled to be in COVID Watch for 14 days, with the option to extend to 21 days if interested. A Spanish-language version of COVID Watch was made available to patients on May 18, 2020, with nurses using translation lines to communicate with patients.~COVID Watch engagement is high. To date, nearly 80% of enrolled patients have engaged with the program, defined as responding to scheduled text messages at least once every two days. RNs have managed over 600 calls with a mean response time (median) of 25 minutes (11 minutes). Of the calls, 37% were asked to continue to monitor at home, 41% were scheduled for an urgent follow-up telemedicine visit, and 9% were sent to the ED for emergent evaluation.~The investigative team provides a conceptual model of how adding home pulse oximetry may potentially improve outcomes. Preventing or aggressively treating respiratory failure is essential for patients infected with COVID-19. Among all infected patients, an estimated 10-20% of patients with COVID-19 develop severe illness requiring hospitalization, of which 30-40% develop critical illness requiring support in an intensive care unit. Among the critically ill, respiratory failure is common and results from acute hypoxemic respiratory failure due to acute respiratory distress syndrome (ARDS). ARDS is a clinical manifestation of pulmonary tissue inflammation, preventing the exchange of oxygen between inhaled air and blood circulating in patients' lungs (hypoxemia). Increasing the concentration of oxygen in the air that patients breathe (e.g., supplemental oxygen) and reducing the degree of pulmonary inflammation can support patients with COVID-19 by reducing the severity of hypoxemia and providing sufficient oxygen supply to vital organs. Measures of pulse oximetry - the oxygen saturation in the blood - can provide an objective measure to identify which patients have or are beginning to experience declines in their respiratory function.~The investigators' conceptual model is based on emerging evidence that early medical interventions can improve clinical outcomes for COVID-19, resulting in less severe clinical sequelae and reduced mortality. For COVID-19 patients requiring supplemental oxygen, new preliminary data from a large multicenter randomized controlled trial of dexamethasone indicates that patients have markedly reduced mortality when given dexamethasone. This corticosteroid likely reduces pulmonary inflammation and prevents the development of severe ARDS. These findings suggest that earlier treatment for patients who develop more severe forms of COVID-19 may prevent unwanted outcomes. Secondly, there is additional evidence that remdesivir can speed recovery and reduce hospital days among patients with COVID-19. Finally, there is promising data that simple changes in ED care and hospital practices may improve outcomes. For example, awake proning, which involves positioning an awake, non-intubated patients at regular intervals onto their abdomen with their face down can enable greater recruitment of lung tissue for oxygen exchange and reduce the need for subsequent intubation and mechanical ventilation. These sorts of interventions can reduce the days that patients spend in the hospital, prevent complications such as ventilator associated pneumonia, and reduce mortality related to COVID-19.~Respiratory decline needs to be identified early for patients to benefit from early medical interventions. Respiratory decline can be (a) signaled when patients report the sensation of feeling shortness of breath or difficulty breathing (i.e., dyspnea), or (b) identified when the concentration of oxygen in patients' blood or oxygen saturation are objectively measured. Current models of care (Usual Care), even with expanded telemedicine access, rely on patients contacting providers - a reactive process. This reactive process can delay care because most primary care practices use an intermediary (e.g., a staff member or message inbox) to screen communications for busy clinicians. Many practices do not respond to patients' concerns efficiently overnight or on weekends. These processes frustrate patients because they are concerned about contacting their providers for mild changes, irrespective of the time or day the event is occurring, because they are concerned about respiratory failure. This process is even harder for patients with limited primary care or telemedicine access or language barriers, problems disproportionately faced by Black and Latino communities. In contrast, COVID Watch is a proactive process, requesting patients report symptoms twice a day, and patients can trigger a phone call to a nurse within an hour by simply texting. COVID Watch + pulse oximetry mirrors COVID Watch but can proactively detect respiratory decline using an objective measure of oxygen saturation. In addition, COVID Watch is available free of charge and is now available in Spanish, with over 85 Spanish speaking patients enrolled to date.~To not overburden emergency departments (EDs), respiratory decline needs to be identified accurately. Both unnecessary escalations of care to the ED for patients with mild COVID-19 and delayed detection of respiratory decline in patients with severe COVID-19 may occur when managing patients with COVID-19. For usual care and COVID Watch, clinicians are reliant on the subjective sensation of dyspnea. Dyspnea is concerning enough that patients are often redirected to an urgent care center or emergency department so patients can have their oxygen saturation measured. Referring patients with an oxygen saturation <94% would justify redirecting patients to the ED for additional clinical evaluation and supportive therapy. Referring patients with mild dyspnea who turn out to have a normal oxygen saturation may be a burden to patients and their families and requires additional resource from EDs and hospitals. During times of rapid rises in community infection rates, or surges, efficient resource allocations are imperative for supporting patients who are critically ill. At the same time, patients still benefit from enhanced connections with clinical providers to reassure them that they are not experiencing respiratory decline. COVID Watch, supplemented by pulse oximetry, could provide this highly responsive team of clinicians objective data so they can accurately assess a patient's respiratory state.~In an alternative scenario, patients may have low oxygen saturation without the sensation of dyspnea, a phenomenon unique to COVID-19 infected patients, and is commonly known as silent or happy hypoxemia. These patients receive medical interventions late because they are unaware they are hypoxemic. There have been reports of COVID-19 patients arriving in EDs with profoundly low oxygen saturation levels with relatively little or no dyspnea. This has led to proposals to use home pulse oximetry to detect silent hypoxemia which have been widely reported in the media (e.g. New York Times) and resuscitation medicine forums. To address this phenomenon, the Vermont Department of Public Health has implemented a program to mail pulse oximeters to newly diagnosed COVID-19 cases 24-48 hours after contact tracing interviews. But as reported in Science: No one, however, has studied whether early detection of hypoxia might head off bad outcomes. Some physicians believe pulse oximeters are best used with a doctor's guidance, perhaps through telemedicine. With many COVID-19 patients frightened to visit a hospital and arriving only when their symptoms have dangerously advanced, doctors also wonder whether home monitoring could hasten treatment-and whether, for some, that could make all the difference.~Based on lack of studies determining whether pulse oximetry can hasten treatment for patients deteriorating at home relative to the current standard of care in the health system of automated text messaging paired with telemedicine, the investigators believe there is equipoise between these two treatment strategies: automated text messaging with telemedicine vs. automated text messaging with telemedicine plus pulse oximetry. Therefore, a randomized comparison is needed to guide health system programs to better address this pandemic.

The clinical guidance for 90 percent of infected COVID-19 adult patients who do not meet eligibility for inpatient admission is to self-isolate. To support these patients, alternatives to in-person care are needed to manage an unpredictable clinical course; identify and intercept patients rapidly deteriorating at home, prevent viral spread during in-person visits; and minimize future surges in emergency departments (EDs). In addition, fingertip pulse oximeters have been proposed to improve in-home early detection of respiratory deteriorations but are untested and the operational infrastructure to support large-scale monitoring is limited.~While telemedicine has been widely adopted during the pandemic as an alternative to conventional outpatient care, limited telemedicine access may be exacerbating observed disparities for Black and Latino patients. In our health system, Black and Latino patients used video-visits 15 percent less often than white patients. Text messaging and phone calls may improve healthcare access for communities of color, but the evidence for these telecommunication modalities to be effective and improve equity are limited.~The University of Pennsylvania Health System (UPHS) developed and deployed COVID Watch to improve access to health care for COVID-19 patients who are self-isolating at home. COVID Watch sends twice-daily, scheduled text messages to assess patients for shortness of breath using a clinical algorithm to determine whether patients need an urgent escalation to a team of dedicated, on-call nurses within one hour. These nurses are supported by an on-call team of clinicians who can conduct urgent phone or video assessments. Patients can also trigger the algorithmic assessment independent of the scheduled messages. As of May 21, 2020, COVID Watch has managed 3,628 COVID-19 patients at home, of which 1,295 are confirmed COVID-19 positive; of these, 61 percent are Black or Latino, higher than the proportion of all UPHS COVID-19 positive patients that are Black or Latino (55 percent).

Patients reactions towards their diagnosis as having COVID-19. The effect of patients' reaction toward their prospect management. How this can make many hazards. Also, obstacle and barrier to better management.~Different factors affecting the response of people toward their diagnosis as COVID-19

Patients reactions towards their diagnosis as having COVID-19. The effect of patients' reaction toward their prospect management. How this can make many hazards. Also, obstacle and barrier to better management.

Over the years, there has been some progress made in reducing stunting in Afghanistan, the prevalence remains high with half of the provinces experiencing rates above the WHO alert threshold. As part of the Country Strategic Plan (CSP), the World Food Programme (WFP) plans to implement a stunting prevention programme in collaboration with Ministry of Public Health (MoPH) through its Public Nutrition Department (PND) in selected locations with stunting rates above 45%. The programme will emphasis on appropriate nutrition support in the '1000 days' window of opportunity with special focus on proven effective nutrition interventions such appropriate breast feeding, complementary feeding, micronutrient supplementation, malnutrition treatment and prevention, WASH. This will therefore take the form of an integrated approach ensuring the targeted beneficiaries are supported to access nutrition assistance as well as other complimentary interventions provided in-kind by study partners or promoted through social and behaviour change communication (SBCC). WFP will target pregnant and lactating women (PLW) and children aged 6-23 months but will also engage men and players that influence maternal infant and young child nutrition practices. Through this programme, children aged 6-23 months will receive lipid-based nutrient supplement - medium quantity (LNS-MQ) to complement their diets while PLW will receive Super Cereal - wheat soya blend with sugar.~An operational research study was embedded in the stunting prevention programme by credible third-party to determine the extent to which the new actions will influence nutrition outcomes and practices. Introducing the provision of SNF, SBCC as well as formulation and adoption of local culturally acceptable recipes for complementary feeding from locally available nutritious food would be new additions to the current Community Based Nutrition Program (CBNP) package in the implementation phase. During the project implementation, emphasis will be placed will be placed on the adoption of the locally formulated complementary foods as well as application of knowledge and practices promoted through the SBCC activities as part of the exit strategy and ensuring a lasting impact of the project.~Therefore, the Centre of Excellence in Women and Child Health, Aga Khan University, Pakistan proposes an operational research study with mix-methods including formative research, quasi-experimental design to evaluate the stunting prevention programme and process evaluations for stronger evidence base on the effectiveness of proposed interventions on prevention of stunting and developing viable programmes on nutrition under real operational conditions.

Over the years, there has been some progress made in reducing stunting in Afghanistan, the prevalence remains high with half of the provinces experiencing rates above the WHO alert threshold. As part of the Country Strategic Plan (CSP), the World Food Programme (WFP) plans to implement a stunting prevention programme in collaboration with Ministry of Public Health (MoPH) through its Public Nutrition Department (PND) in selected locations with stunting rates above 45%. The programme will emphasis on appropriate nutrition support in the '1000 days' window of opportunity with special focus on proven effective nutrition interventions such appropriate breast feeding, complementary feeding, micronutrient supplementation, malnutrition treatment and prevention, WASH.

Comparison of effect of Prophylactic Negative Pressure versus Silver Impregnated Silicone Bandage on Cesarean Section Surgical Site Infection Rate as compared to wound vacuum in high risk women and traditional border dressing in low risk women in adult women having uncomplicated cesarean section.

Effect of Prophylactic Negative Pressure versus Silver Impregnated Silicone Bandage on Cesarean Section Surgical Site Infection Rate

Cardiovascular diseases represent one of the main causes of death in the Brazilian population, as well as dysfunctions of the heart conduction system. In an attempt to treat and correct heart conduction system dysfunctions, Cardiac Electronic Implantable Device (CEID) was developed. Most people with CEID have a perception of describing the lifestyle due to a limitation of daily activities and physical exercise, besides the consequences in the psychological aspects such as anxiety and depression. These changes in the psychosocial conduct of patients with CEID are due to the lack of knowledge and the lack of effective guidance, being of fundamental importance to elaborate the resources of education in health for patients with CEID. Health promotion through educational intervention is a recognized strategy and an Internet approach to the mobile health proposal is a recognized and promising practice.~This randomized controlled study is been conducted to verify the effectiveness of the Mobile Health of lifestyle that focuses on aspects of physical functional, psychosocial, and quality of life of patients with CEID. The hypothesis is that the use of Mobile Health of lifestyle provides greater physical functional, psychological aspects, and quality of life to patients with CIED.

Previous studies suggested that most patients with Cardiac Electronic Implantable devices have a perception of describing the lifestyle due to a limitation of daily activities and physical exercise, besides the consequences in the psychological aspects such as anxiety and depression. The MHOL-CEID is a randomized controlled trial that Verifies the effectiveness of the Mobile Health of lifestyle that focuses on aspects of physical functional, psychosocial, and quality of life of patients with Cardiac Electronic Implantable Device.

In this open-label, multi-center, observational, post-marketing surveillance study, patients with ankylosing spondylitis, psoriatic arthritis, or rheumatoid arthritis received biosimilar etanercept 25 mg twice weekly or 50 mg once weekly in real-world settings. Safety and effectiveness of biosimilar etanercept were evaluated in study participants for a duration of up to 12 months. Patient information was recorded in four notebooks, and each notebook had three sections, one section for each month. The first section of notebook I contained demographic information, pregnancy and lactation status in female patients, cigarette smoking and alcohol consumption, and past medical history. All safety and effectiveness outcomes were recorded at the appropriate sections of the notebooks.

In this open-label, multi-center, observational, post-marketing surveillance study, patients with ankylosing spondylitis, psoriatic arthritis, or rheumatoid arthritis received biosimilar etanercept 25 mg twice weekly or 50 mg once weekly in real-world settings. Safety and effectiveness of biosimilar etanercept were evaluated in study participants for a duration of up to 12 months.

This study is a multi-center, double-blinded, randomized, placebo-controlled, phase 2 clinical trial to assess the safety and efficacy of sirolimus in patients with active systemic lupus erythematosus despite receiving standard background therapy.~Six large rheumatological referring centers across from China will participate in the study.~The study is divided into two phases. The first phase is a 24-week randomized, double-blinded, placebo-controlled trial, from which the primary end point will be generated, and the second phase is a 24-week open-labeled extension trial.~The study enrolls SLE patients between 18~65 years old who have SLEDAI-2K score ≥4 (not including scores for anti-dsDNA antibody and hypocomplementemia), despite conventional treatment (e.g., immunosuppressants, antimalarial drugs, glucocorticoids, NSAIDs, anti-hypertensive drugs, and/or topical medications). In addition, subjects must be serologically active (positive anti-dsDNA antibody and/or hypocomplementemia.~Subjects will be randomly assigned by 1:1 ratio to receive sirolimus (1.5mg/day) or placebo for the first 24-week phase. In the second 24-week open-labeled phase, sirolimus patients receive the same dose of sirolimus, and placebo group are switched to receive sirolimus at 1.5mg/day

This is a multi-center, double-blinded, randomized, placebo-controlled, phase 2 study to evaluate the efficacy and safety of sirolimus administered in addition to standard therapy, in patients with active SLE disease.

Critically ill patients, who are mechanically ventilated, suffer not only from their acute, potentially devastating illness, but also from the lack of ability to communicate in an effective manner. This is the direct result of the orotracheal tube or tracheostomy required for the mechanical ventilation, which does not allow speech to be produced. On top of the mechanical change in air flow, communication challenges result from sedation, neurological injuries (primary brain injury or secondary encephalopathy), and delirium.~Lack of communication can lead to increased frustration, anxiety, and overall psychological stress and could continue to the development of post-traumatic stress disorder (PTSD). On top of the subjective discomfort, the inability to communicate in an effective manner may impair medical care-for example, by failure to assess symptoms such as pain or breathing discomfort by behavioral cues only.~Currently, the solutions for communication deficits in mechanically ventilated patients are mainly using yes/no communication, attempting to write, and communication boards that allow people to point at defined pictures or letters. Recently, technological advancements led to incorporation of more sophisticated communication devices, proving the feasibility of an eye-tracking approach, for example.~The EyeControl is a new, wearable, eye-tracking device that facilitates communication by means of internal feedback to the patients with a bone-conducting speaker. In this way, the device can ask the patient what he or she wants to say, and the patient replies by eye gestures such as blinking or moving the eyes in a certain direction. This approach eliminates the need for calibration, as most eye-tracking devices that use a screen require, and is relatively easy to operate.~This study will assess the safety, tolerability, and ease of use of the EyeControl device.

The purpose of this study is to evaluate the feasibility of use of a wearable communication device for critically ill patients who are admitted to the intensive care unit (ICU) and mechanically ventilated. The study will assess the safety, tolerability, and ease of use of the EyeControl device, and examine its potential monitoring capabilities.

This is a Phase 1/2 study to evaluate the safety and potential efficacy of agenT-797, an unmodified, allogeneic invariant natural killer T (iNKT) cell therapy, in participants with moderate to severe ARDS secondary to SARS-CoV-2 or influenza, either with intubation or at high risk to be intubated, as determined using Berlin definition(s).~Part 1 will employ a standard 3+3 dose escalation design of agenT-797. All participants will receive a single infusion of agenT-797. Participants will also receive other treatments and supportive care per discretion of the investigator. Once the maximum tolerated dose of agenT-797 has been cleared in Part 1, an Expansion Cohort will be opened.~A safety monitoring committee will be established to assess safety and decide on escalation to next cohort and expansion dose, as well as any protocol modification to include less severe cases.

A Phase 1/2 study of agenT-797 to treat moderate to severe acute respiratory distress syndrome (ARDS) secondary to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza.

This is a randomized prospective open-label cohort study in patients with COVID-19 to evaluate the impact of Oscillation and Lung Expansion (OLE) therapy using The MetaNeb® System on the hospital length of stay in patients hospitalized and receiving heated high-flow oxygen therapy for COVID-19 infection. The active treatment group will consist of patients who are treated OLE therapy while on heated high-flow oxygen therapy .~Results from subjects in the active treatment group will be compared to results from patients treated with standard care with no OLE therapy.

A Pilot Study of the Use of Oscillation and Lung Expansion (OLE) Therapy in Patients Hospitalized with COVID-19

This is a Phase I prospective, open label, non-randomized opportunistic study to evaluate the PK and safety of RDV when administered to pregnant and non-pregnant women of childbearing potential for treatment of COVID-19. RDV is not provided as part of this study; a requirement for entry is that participants receive RDV as part of their clinical care (i.e., outside of the study). A target of 20 PK evaluable pregnant women will be enrolled into Arm 1; a target of 20 PK evaluable non-pregnant women of childbearing potential will be enrolled into Arm 2. Study sites will be located in the United States.~Participants will be pregnant and non-pregnant women hospitalized for COVID-19 and will receive daily RDV infusions, typically for 5 days but in some cases for up to 10 days, as part of their clinical care. RDV will be provided and managed by the participants' treating physician and will not be provided as a part of this study. Participants will undergo intensive PK sampling.~For all women, clinical and laboratory evaluations will be abstracted from the medical record. Pregnancy, birth, and infant outcomes will be obtained from pregnant women enrolled in Arm 1. Women will be followed for safety through 4 weeks after the last infusion; Arm 1 women who are still pregnant at that time will also be followed for safety at delivery.

The purpose of this study is to describe the pharmacokinetic (PK) properties and safety of remdesivir (GS-5734TM) (RDV) administered to pregnant and non-pregnant women with COVID-19. It is a Phase I, prospective, open label, non-randomized opportunistic PK study in pregnant and non-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19. RDV will not be provided as part of the study.

Lung transplant recipients are at high risk for lung rejection and lung infection after transplant. This is diagnosed by performing lung bronchoscopies and lung biopsies. These procedures carry an increased risk for complications and are costly. This study is being done to study a safe and non-invasive way to diagnose lung rejection and infection.

This study is being done to study a safe and non-invasive way to diagnose lung rejection and infection.

This is a single center, double-blind (patient and investigator), randomized, placebo-controlled study with a split-lesion design.All study procedures will be performed at the Department of Dermatology, Erasmus MC Medical Center in patients referred for scar treatment to our outpatient clinic.~Clinical photos will be obtained after signing the informed consent form by patient and investigator. Study visits and clinical assessments will be scheduled at baseline, 4 weeks, 8 weeks, and 12 weeks. Measurements include clinical photography, scar volume measured by 3D-camera, POSAS questionnaire, laser speckle contrast imaging to visualize keloid scar vascularization, measurement of residue formation on the skin, and a treatment related questionnaire. The keloid will be divided into two treatment areas, and randomly assigned to three consecutive treatments of: a) bleomycin and b) placebo (saline (NaCl 0,9%)), administered with an electronic pneumatic jet injector.

This is a single center, double-blind (patient and investigator), randomized, placebo-controlled study with a split-lesion design, in which selected keloids will receive three consecutive treatments of a) bleomycin and b) placebo (saline (NaCl 0,9%)), administered with an electronic pneumatic jet injector.

This study is a randomized, double-blinded, multi-center, placebo-controlled phase III clinical trial in adults aged 18~59 years. The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the experimental SARS-CoV-2 inactivated vaccine. The experimental vaccine and placebo were both manufactured by Sinovac Research & Development Co., Ltd. A total of 13.000 subjects will be enrolled. Participant will be assigned to receive two doses of experimental vaccine or placebo on the schedule of day 0,14. It is planned that the study will be conducted with two separate cohorts. The first cohort will be healthcare workers in the high risk group (K-1) and the second cohort will be people at normal risk (K-2). After 2 doses of vaccination of 1300 volunteers are completed, safety data will be evaluated by the data safety monitoring board without breaking the blinding, and if there is no safety issue, the K2 cohort will continue to be vaccinated.1.300 volunteers, including 650 volunteers SARS-CoV-2 vaccine and placebo arms, will be included in the K-1 cohort. In the K-2 cohort (normal risk group for COVID-19), 7.650 volunteers were planned to be included in the SARS-CoV-2 vaccine group, and 3.500 volunteers in the placebo group.

This study is a randomized, double-blinded, and placebo controlled phase III clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the experimental vaccine in healthy adults aged 18~59 Years.

Participants will be randomized and assigned to one of the following 2 treatment arms in a ratio of 5:1:~Arm 1: HSY244 intravenous infusion Arm 2: Placebo intravenous infusion~The study consists of a screening period of up to 3 days and a treatment period of 5 days. After confirming eligibility and pre-dose assessments are completed on Day 1, study administration will occur and participants will be monitored for cardioversion to sinus rhythm. During the treatment period, participants will be evaluated for efficacy, safety, tolerability, and pharmacokinetics.

The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics of HSY244 in participants with atrial fibrillation (AF), with and without heart failure (HF).

This is a biological study for R/R T-ALL/LBL or ETP-ALL patients. Bone marrow and/or peripheral blood samples will be subjected to genomic, DSRP profiling and phosphoproteomic screening to identify novel potential therapeutic approach and thus, eligibility for treatment based on molecular and DSRP data.~Genomic studies include karyotyping, CI-FISH and sequencing of 72 selected genes recurrently involved in T-ALL (by NGS).~A panel of 80 compounds has been choosen for DSRP profile.~As soon as genomic and DSRP profiling are made available, local Investigator can submit to local ethic committee a request for clinical use of compound hits. Meanwhile, in case of leukocytosis and uncontrolled disease, patients will be treated with cytoreductive therapies and best supportive care according to guidelines and scientific consensus.~Every patient will receive a molecularly and functionally informed therapy following the therapeutic schedule already defined by in other tumors. Treatment will be selected on the basis of integration of genomic and small response data.

This is a biological study for R/R T-ALL/LBL or ETP-ALL patients. Bone marrow and/or peripheral blood samples will be subjected to genomic, DSRP profiling and phosphoproteomic screening to identify novel potential therapeutic approach and thus, eligibility for treatment based on molecular and DSRP data. As soon as genomic and DSRP profiling are made available, local Investigator can submit to local ethic committee a request for clinical use of identified compound.

Allogeneic hematopoietic stem cell transplantation should be offered to eligible patients with high risk hematological malignancies whenever feasible. To further improve the outcome of transplantation patients with high risk hematological malignancies, the investigators developed a modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine. In this study, the investigators tested the efficacy and feasibility of the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine in Patients with high risk hematological malignancies undergoing allogeneic peripheral blood stem cell transplantation.

The purpose of this study is to determine the efficacy and safety of Ruxolitinib and Decitabine intensified Conditioning Regimen in Patients with High Risk hematological malignancies undergoing allogeneic peripheral blood stem cell transplantation.

Background~Surgery is a risk factor for acute kidney Injury (AKI). Surgery exposes patients to hypotension, sepsis, the infusion of blood products, ischaemia, oxidative stress and reperfusion injury.~Patients who develop AKI post operatively are susceptible to fluid overload, infections, and cardiac events. AKI confers an increased risk of chronic kidney disease and mortality. Studies assessing rates of AKI in general surgical patients place the frequency at 1-14%.~Established methods of assessing for AKI - products of nitrogen breakdown and urine output - have limitations. Serum creatinine and urea are affected by sex, nutritional status, blood in the gastrointestinal tract, and fluid resuscitation. Rises in serum creatinine become apparent once glomerular filtration has reduced by half. This potentially delays the use of reno-protective strategies.~Novel biomarkers have been investigated. These aim to verify the use of renal biomarkers as a method of identifying AKI more rapidly: It is hoped that reno-protective strategies could be adopted sooner.~Much work has concerned cardiac and transplant surgery. AKI rates have been quoted as high as 30% in this cohort. Results were initially encouraging for various biomarkers. One biomarker (Insulin like growth factor binding protein number 7 / Tissue inhibitor of metalloproteinases 2 - IGFBP-7/TIMP-2) has therefore been incorporated into Enhanced Recovery Programmes in such patients.~While research in cardiac and transplant surgery has been extensive, it has been limited with regards to abdominal surgery. Although rates of AKI are lower in this cohort, they still bear a significant burden of disease. At present, no biomarker has been found to be clinically useful in this setting.~Study Objectives~Primary~The validation of Urinary Biomarkers for use in the prediction of AKI in major abdominal surgery patients~Secondary~To assess the role different surgical sub-types and peri-operative factors have in causing AKI in Major Abdominal Surgery patients~Trial design~This is an observational study that will assess the use of Urinary biomarkers against conventional methods of assessing for AKI, the Kidney Disease, Improving Global Outcomes (KDIGO) criteria. The KDIGO criteria is based on increases in serum creatinine and reduction in urine output.~The biomarkers are:~IGFBP-7/TIMP-2 Neutrophil Gelatinase Associated Lipocalin (NGAL) Kidney Injury Molecule 1 (KIM-1) Dickkopf related protein 3 (DKK-3)~All patients undergoing major elective general surgery, and major abdominal gynaecological surgery will be included. All patients will have a urine sample taken 4 hours post operatively. This sample will be tested using the biomarkers. Written consent will be obtained from all participants.~The consent form has been designed with help of 10 surgical inpatients and 4 surgical nurses to ensure ease of understanding and a lack of medical jargon.~No changes are required to standard patient care. The urine sample obtained will be a catheter specimen.~Comparison of the novel biomarkers against conventional methods will be conducted using the KDIGO criteria. This entails regular urine output measurement, assessment of blood urea, electrolytes, and estimated glomerular filtration rate. Data regarding patient, operative and post-operative characteristics will be recorded on a purpose-built secure hospital intranet database.~Data Analysis~Performance of the biomarkers will be assessed using multiple logistic regression, and by conducting 'area under the receiver-operator curve (AUROC)' analysis. A risk prediction model will be created based on patient factors strongly associated with the primary endpoint. The performance of the risk prediction model will be assessed as a standalone test and in conjunction with the novel biomarker tests.~The sample size was calculated on the basis of previously published AUROC values for the test, the expected prevalence of AKI, and a desire for a 95% confidence interval around the calculated AUROC estimate for the study. This results in a target sample size of 471.~Hoped Aims of Research~The researchers hope that a novel test is found that can identify AKI sooner in an at-risk cohort of patients. If so, a further trial is intended: post-operative patients who are positive to the novel test will be randomised to a kidney protective 'bundle', and rates of AKI compared.~Ultimately, the intention is to greatly reduce a significant cause of post-operative morbidity, surgical complications, and mortality, through the judicious use of a non-invasive test.

To validate Urinary Biomarkers for the prediction of AKI in major abdominal surgery patients

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, resulting in a social and economic burden that is substantial and increasing. Exacerbations affect the prognosis and quality of life of patients with COPD. Hospital mortality of patients admitted for a hypercapnic exacerbation of COPD is approximately 10% and the long-term outcome is poor. In addition, hypercapnic exacerbation of COPD have serious negative impacts on patient quality of life, lung function and costs. Thus, prompt treatment of exacerbations may impact the clinical progression of COPD by ameliorating quality of life and prognosis.~The pathophysiological hallmarks of COPD patients include expiratory flow limitation and small airway closure. Under these circumstances, a prolonged expiratory time is the compensatory mechanism patients adopt to maintain a stable tidal breathing. COPD exacerbations result in higher respiratory rates and reduced expiratory time, leading to dynamic hyperinflation, elevated intrathoracic pressures, and excessive work of breathing. Alteration of the balance between (a) the decreased capacity of the respiratory muscles to generate pressure, and (b) the increased mechanical respiratory load due to expiratory flow limitation and small airway closure leads to CO2 retention. The consequent reduction of alveolar ventilation leads to a further worsening of CO2 retention and increased work of breathing. This vicious circle is the underlying mechanisms responsible of acute respiratory failure requiring admission in the intensive care unit (ICU) for ventilatory support.~Standard of care for patients with COPD exacerbation that need ICU admission for management of acute hypercapnic respiratory failure and severe respiratory acidosis is non-invasive ventilation (NIV). When NIV fails (arterial pH remains < 7.30), invasive ventilation through endotracheal intubation is initiated to restore adequate gas-exchange.~Extracorporeal circuits designed to remove CO2 (ECCO2R) have been used in patients with acute hypercapnic respiratory failure since ECCO2R may enhance the efficacy of NIV to remove CO2 and avoid the worsening of respiratory acidosis. Although available studies are limited to case series, several ECCO2R devices have been developed and proposed for the clinical use in patients with COPD. These systems often represent modifications of renal replacement therapy circuits, and are characterized by:~veno-venous by-pass systems~extracorporeal blood flow of 0.3-0.5 litres/min~13 Fr bore catheters or a single co-axial catheter~very low doses or no heparin~minimal volumes for priming~This technological implementation of ECCO2-R is therefore closer to device for renal replacement therapy than full ECMO. CO2 is removed through a double-lumen catheter and constantly propelled, by a non-occlusive rotating pump, though an artificial membrane lung (a filter adding oxygen and removing carbon dioxide) connected to a source of 100% O2 (flow 6-8 liters/min). These systems are able to reduce PaCO2 by 20-25%.~A recent matched cohort study with historical control, compared NIV-plus-ECCO2R and NIV-only in patients at risk of NIV failure, and showed that (a) the hazard of being intubated was three times higher in patients treated with NIV-only than in patients treated with NIV-plus-ECCO2R; (b) hospital mortality was significantly lower in NIV plus ECCO2R than in NIV-only [8% (95% CI 1.0-26.0%) vs. 33% (95% CI 18.0-57.5%), respectively]. However, ECCO2R-related complications were observed in almost half of the patients. A recent systematic review evaluated the efficacy and safety of ECCO2R in patients with hypercapnic respiratory failure across 12 studies and showed that the majority of patients were either successfully weaned from mechanical ventilation or sustained on NIV, avoiding intubation. However, this high success rates, was associated with a high frequency of potentially severe complications.~The consistency of the above discussed data, and the observation of the continuous increase use of ECCO2R despite the lack of solid evidence confirm that the equipoise regarding the use of ECCO2R may justify a randomized clinical trial to evaluate whether patients with respiratory acidosis refractory to NIV should be intubated and take the risks associated with invasive mechanical ventilation, or should be connected to ECCO2R to avoid intubation, but run the risk of the potentially serious ECCO2R-related complication~Objectives:~The main objective of this randomized multicenter clinical trial is to test the hypothesis that in patients with acute life-threatening exacerbation of COPD, use of ECCO2R could increase event-free survival as compared to standard of care. Event free survival is defined as survival at day 28 free of any of the followings: (a) development of sepsis; (b) occurrence of a second episode of COPD exacerbation requiring or not mechanical ventilation; (c) occurrence of severe hypoxemia; (d) prolonged mechanical ventilation (e) death.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, resulting in a social and economic burden that is substantial and increasing. Exacerbations affect the prognosis and quality of life of patients with COPD. Hospital mortality of patients admitted for a hypercapnic exacerbation of COPD is approximately 10% and the long-term outcome is poor. In addition, hypercapnic exacerbation of COPD have serious negative impacts on patient quality of life, lung function and costs. Thus, prompt treatment of exacerbations may impact the clinical progression of COPD by ameliorating quality of life and prognosis.~Standard of care for patients with COPD exacerbation that need ICU admission for management of acute hypercapnic respiratory failure and severe respiratory acidosis is non-invasive ventilation (NIV). When NIV fails (arterial pH remains < 7.30), invasive ventilation through endotracheal intubation is initiated to restore adequate gas-exchange. Extracorporeal circuits designed to remove CO2 (ECCO2R) may enhance the efficacy of NIV to remove CO2 and avoid the worsening of respiratory acidosis.~A recent matched cohort study with historical control, showed that: (a) the hazard of being intubated was three times higher in patients treated with NIV-only than in patients treated with NIV-plus-ECCO2R; (b) hospital mortality was significantly lower in NIV plus ECCO2R than in NIV-only [8% (95% CI 1.0-26.0%) vs. 33% (95% CI 18.0-57.5%), respectively]. However, ECCO2R-related complications were observed in almost half of the patients.~The consistency of the above discussed data, and the observation of the continuous increase use of ECCO2R despite the lack of solid evidence confirm that the equipoise regarding the use of ECCO2R may justify a randomized clinical trial to evaluate whether patients with respiratory acidosis refractory to NIV should be intubated and take the risks associated with invasive mechanical ventilation, or should be connected to ECCO2R to avoid intubation, but run the risk of the potentially serious ECCO2R-related complication The main objective of this randomized multicenter clinical trial is to test the hypothesis that in patients with acute life-threatening exacerbation of COPD, use of ECCO2R could increase event-free survival as compared to standard of care.

Stroke is the second leading cause of death and one of the main contributors to disability. Patients who survive the acute phase of ischemic stroke and those with a transient ischemic attack (TIA) are at high risk of subsequent stroke. Importantly, recurrent strokes are associated with a higher social and economic impact, higher case fatality, and worse clinical outcome than first-ever strokes. The burden of post-stroke complications, residual deficits, and inadequate medical and psychosocial care all contribute to long-term disability and reduced quality of life in these patients. Furthermore, effects on quality of life and long-term functional independence are particularly under-investigated.~The Department of Neurology of the Medical University Innsbruck undertook the STROKE-CARD trial (NCT02156778) between 2014 and 2018 with follow-up until 2019 to evaluate the efficacy of the Post-Stroke disease management program STROKE-CARD care. The aim is to evaluate this program in a large multicenter cohort and to establish a biobank of stroke and TIA-patients for future research and development projects.~In brief, the pragmatic and easily implementable STROKE-CARD care program reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischemic stroke or TIA in a timeframe of 12 months after the index event. To investigate the effects of STROKE-CARD care on a large basis and over a longer period, an evaluation of approximately 5,000 patients is warranted.~Whereas disease management programs typically rely on expert opinion, the STROKE-CARD initiative moved from a purely empirical approach to a highly structured, individualized, and evidence-based procedure with professional outcome analysis. The STROKE-CARD concept will be implemented in clinical practice and can serve as a model for other disease management initiatives.~Acute and short-term management of stroke and TIA has improved tremendously over the past years with substantial advances in acute therapy, implementation of comprehensive pathways for stroke and TIA, and approval of novel highly effective preventive treatments. As a main unmet challenge in stroke medicine, strategies of long-term care have to be developed and rigorously tested in order to maintain improved short-term patient outcome in the long run.~STROKE-CARD care reduced the one-year cumulative absolute risk of CVD and ameliorated the patients' health-related quality of life at 12 months (EQ-5D-3L overall utility score, P<0.001). These findings were consistent in subgroups according to age, sex, and index event and were robust in the per-protocol analysis. Among pre-specified secondary outcomes assessed at 12 months, the investigators observed improvements in all individual dimensions of the EQ-5D-3L and in one-year functional outcome, that each met the multiplicity-adjusted threshold for statistical significance. Only a few previous trials of disease management programs in stroke and TIA patients have focused on recurrent CVD or quality of life as primary or secondary endpoints and none has considered long-term functional outcome after one year. The previous trial was limited to a 12-month follow-up in selected individuals and the sustainability of benefits of STROKE-CARD care in a large nationwide cohort over a longer follow-up period remains to be determined.~This study aims to detect post-stroke complications, to estimate the patient's demand for nursing services, and support guideline-compliant secondary prevention with full achievement of target levels, lifestyle modifications, and in-person outcome assessment at 3 and 12 months after the index-event, assessment of functional status (impairment), activity (disability), and participation (handicap and health-related quality of life). Additionally, yearly follow-up telephone interviews for cardiovascular outcome and health parameters will be conducted. In case of clinically indicated in-person follow-ups, the interviews will be done in person during the clinical visits. After the implementation of STROKE-CARD care, the investigators aim to document the quality of post-stroke care and compare outcome parameters to historical cohorts and the change over time. Furthermore, the investigators aim to gain a large data resource for future research of biomarkers, disease mechanisms, prognosis and imaging mechanisms for R&D.~The main objective is to evaluate the Post-Stroke Disease Management program STROKE-CARD in a large multicenter cohort of stroke and TIA-patients and to establish a large clinical well-defined cohort. Furthermore, the investigators aim to gain a large data resource for future research of biomarkers, disease mechanisms, prognosis and imaging mechanisms for R&D.~To document and monitor the quality of the Post-Stroke Disease Management program in different centers and compare outcomes to the historical cohort, as well as other published data. Furthermore, the investigators aim to constantly improve post-stroke care. This registry can facilitate to monitor and document the effect on the primary and secondary outcomes.~There will be no formal safety endpoints in this study. No experimental procedures will be applied to patients and most of the procedures done are within the clinical routine. Potential side effects of optimal secondary stroke prevention are recorded.

Stroke is the second leading cause of death and one of the main contributors to disability. Patients who survive the acute phase of ischemic stroke and those with transient ischemic attack (TIA) are at high risk of subsequent vascular events. Importantly, recurrent strokes are associated with a higher social and economic impact, higher case fatality, and worse clinical outcome than first-ever strokes. The burden of post-stroke complications, residual deficits, and inadequate medical and psychosocial care all contribute to long-term disability and reduced quality of life in these patients. The Department of Neurology of the Medical University Innsbruck undertook the STROKE-CARD trial (NCT02156778) between 2014 and 2018 with follow-up until 2019 to evaluate the efficacy of the Post-Stroke disease-management program STROKE-CARD care. After implementation of STROKE-CARD care, the investigators aim to document the quality of post-stroke care and compare outcome parameters to historical cohorts and the change over time. Furthermore the investigators aim to gain a large data-resource for future research of biomarkers, disease mechanisms, prognosis and imaging mechanisms for R&D.

This study plans to evaluate the clinical benefits of fruquintinib combined with raltitrexed compared with fruquintinib single drug treatment in patients with advanced colorectal cancer who have failed second-line or above treatment, in order to explore the rationality of this strategy with chemotherapy + targeted combination therapy and obtain the relevant survival and safety data. A total of 136 patients were planned to be enrolled in this study.

A randomized, controlled phase II clinical trial of Fruquintinib combined with Raltitrexed versus Fruquintinib monotherapy in patients with advanced colorectal cancer who had failed second-line or above standard chemotherapy

This is a phase II clinical trial. The purpose of this research is to study the safety and efficacy of Camrelizumab treating patients with newly diagnosed glioblastomas. Neoadjuvant PD-1 inhibitor will be administered to patients with newly diagnosed glioblastomas, followed by surgical resection, standard radiochemotherapy, and further PD-1 inhibitor treatment.

The purpose of this research is to study the safety and efficacy of Camrelizumab treating patients with newly diagnosed glioblastomas.

Participants~Seventy-four healthy subjects participated in this study (37 male and 37 female). Healthy subjects were selected because ankle injuries frequently occur during normal locomotion; and most people, not only athletes, experience an ankle injury at least once during their entire life.25,27~Before starting this study power test was performed to determine the number of participants. Participant's age range was 18 - 30 years old and participants were recruited from university population, Participants were divided randomly into two groups (Taping group n=37) and (Bandaging group n=37. Participant were excluded if he/she reports (a) previous hip/pelvis, knee, ankle, or foot surgery within the past year; (b) lower extremity amputation; (c) injury to the lower extremities six months; (d) known balance impairment due to neurological disorder, vestibular disorder, medication use, or other; (f) pregnancy; or (g) concussion within the previous three months. Standard clinical stability testing of the ankle ligamentous structures was performed to rule out anterior and lateral talocrural joint instability and lower extremity injuries during the previous 6 months. Each volunteer signed an informed consent form before participation. This study was approved by Dokuz E|ylul university ethics committee.~Procedures Leg length was measured (right and left leg) while participant lying supine, from the anterior superior iliac spine to the inferior border of the ipsilateral medial malleoli by using standard measure tape. The dominant leg was determined according to Vauhnik. & ark. modified version. The limb that was used in at least 2 of the 3 following activities: (1). Kicking a ball, (2). Drawing a diamond figure on the ground and (3).using his leg and step over a spider toy, was considered as the dominant leg.30~Ankle taping Procedures Zinc oxide tape has been was used, its hard - preventive tap. The taping procedure consists of three separate steps: The first step involved the application of the anchor tape, which achieved by applying the tape circumferentially just above the malleolar level at the lower end of the shank. The second step involved the application of the stirrup. During this step, the foot was held in neutral, and the tape applied to pass from the medial side of the ankle, under the foot just over the heel area (posterior one-third of the foot) and up along the lateral side of the ankle. The second step was repeated to apply the second stirrup. Both ends of the stirrups were firmly attached to the anchor tape applied during the first step and this attachment was reinforced with a locking tape during the third and final step by once again applying the tape circumferentially just above the malleolar level at the lower end of the shank. The taping was applied by a physical therapist according to the health association requirements.23~Ankle bandaging Procedures Standard 10 cm width elastic bandage was used. The elastic bandage was wrapped around the ankle joint to form an 8-figure shape starting from the forefoot. Then the bandage is taken diagonally upwards, steeply enough to go well above the heel, then around the lower calf area to form an anchor, then diagonally down across the midfoot, again wrapped around the forefoot and going diagonally up to finish off around the lower calf, leaving the heel open.9 Then the participant was allowed to wear his/her sport shoes over the bandage during the measurement procedures.~Balance measurement Procedures Star Excursion Balance Test (SEBT) is a field test and widely used to assess dynamic postural control, and has an excellent interrater reliability (ICC = 0.86 - 0.92)12. In thıs study the SEBT was used to evaluate balance. 8 strips of athletic tape with a length of 6 feet were used. Then a '+' sign was formed. Then 'x' sign was formed with the other two strips. The lines were separated from each other by an angle of 45°. The participant was asked to wear sports clothes and take off the shoes, then to step on the center of the grid formed by eight lines using the dominant leg, the plantar aspect of the first metatarsophalangeal joint (ball of the foot) was positioned on the intersecting lines at the center of the grid to maintain consistency in foot placement. The participant starts to reach as possible as far in the eight lines, make a light touch on the line, and return the reaching leg back to the center, while maintaining a single-leg stance with the other leg in the center of the grid, starting from anterior direction and progressing clockwise. The order of the directional reaches was as follows: A, AM, M, PM, P, PL, L, AL. When reaching in the lateral and posterolateral directions, participants must reach behind the stance leg to complete the task.13~The participant practiced 6 training attempts to reduce the learning effect, and then after 5-min of rest period participant performed 3 trials in each of the 8 directions, 5-min of rest period was taken between each one of the three trials. The researcher recorded the reaching distance using standard tape measure by marking the tape as the distance from the center of the gird to the maximal reaching point, the average of these three attempts was calculated and then normalized to the leg length, the obtained result used in the statistical analysis. If the participant used the stance leg for a high amount of support, was unable to maintain balance on the stance leg, or removing his feet from the center any time while doing the trial, the attempt was canceled and repeated again. In the case of a rejected trial, verbal feedback was given to the participants so they attempt to correct the performance error(s) on the next trial.13~The balance measurements were done 4 times, (before ankle taping, after 20 minutes while using ankle taping, after 24 hours while using ankle taping and immediately after removing the tap (after 24 hours).~Proprioception measurement Procedures Invistigators used the measurement procedure which described in the study which was doneIris et al23. by The first step: volunteers were seated in a high chair, and while their eyes are closed, the researcher consecutively on different graduated surfaces (10° dorsiflexion, neutral position, 10° plantarflexion, and 20° plantarflexion) respectively, each position will be done for just one time and will be held for 5 seconds. The researcher told the volunteers that they have to memorize the positions because they have to do it again by themselves. Simultaneously, each joint position was recorded to obtain the target angle using the universal goniometer. This was the angle that the volunteer was instructed to reproduce during the testing part of the study. The second step: The volunteer was then encouraged to walk freely next to the researcher for 10 minutes, still blindfolded. The third step: Then the volunteer sat on a high chair that did not allow his or her feet to touch the floor (to avoid any information from the sole). Finally, the researcher encouraged the subject to reproduce the four memorized positions, starting from and finishing in the neutral position each time. The volunteer maintained each ankle position, announced by the researcher at random, for five seconds. The volunteer's ankle movement was recorded using the universal goniometer, and this reproduced ankle angle was called the estimated angle.~The difference between the learned positions and the positions that were done by the volunteer was calculated and documented. Deviation from the learned angle (degrees) described the direction of Error when subjects tried to reproduce the requested position. Deviation was obtained by coding net Error, which was based on the correct position occurring when the learned and estimated angle were equal (±5 degrees)23.~The position (ROM) measurements were done on four occasions, (before ankle external support, after 20 minutes while using external support, after 24 hours while using external support and immediately after removing the external support (after 24 hours).

Leg length was measured (right and left leg) while the participant lying supine, from the anterior superior iliac spine to the inferior border of the ipsilateral medial malleoli by using standard measure tape. The dominant leg was determined according to Vauhnik. & ark. modified version. The limb that was used in at least 2 of the 3 following activities: (1). Kicking a ball, (2). Drawing a diamond figure on the ground and (3).using his leg and step over a spider toy was considered as the dominant leg.30

The role of micro-RNAs in chronic periodontitis associated with CAD is still in an incipient stage needs to be explored further. The investigators attempt to quantify and compare the levels of micro-RNA 146a and micro-RNA 126 in subgingival as well as coronary plaque samples obtained from patients diagnosed with chronic periodontitis with and without coronary artery disease.~Seventy-five participants were selected and grouped into 3 categories; 25 patients diagnosed with chronic periodontitis and coronary artery disease: CP + CAD group; 25 patients diagnosed with chronic periodontitis alone: CP group; and 25 systemically and periodontally healthy controls (HP). Demographic variables, periodontal parameters, cardiac parameters, blood pressure were obtained. miRNA-146a and miRNA126 levels were assessed in subgingival plaque (SP) samples from all the three groups. Within CP+CAD group, SP samples of CP+CADa were compared with coronary plaques samples (CP) of CP+CADb while the patient underwent CABG.

The role of micro-RNAs in chronic periodontitis associated with CAD is still in an incipient stage needs to be explored further. The investigators attempt to quantify and compare the levels of micro-RNA 146a and micro-RNA 126 in subgingival as well as coronary plaque samples obtained from patients diagnosed with chronic periodontitis with and without coronary artery disease.

A randomized, double-blind, single-dose by intravenous administration, placebo-controlled, dose escalation, first-in-human study is proposed to evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics and immunogenicity of HLX71 in healthy subjects. Investigators plan to enroll 10 subjects in each of the 4 dose cohorts at 2.5 mg/kg, 5 mg/ kg, 10 mg/kg and 15 mg/kg, of which 2 receive intravenous injections of placebo and 8 receive intravenous injections of the investigational product (IP). A total of 40 subjects will be enrolled.

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of HLX71 in Healthy Adult Subjects

Primary Objectives~• To examine acceptability, patterns of use, rates of adherence, safety , and measured levels of drug when high risk MSM are provided open-label TDF/FTC for PrEP in South Korea~Secondary Objectives~To evaluate HIV incidence among study participants~To evaluate risk behavior and risk compensation among study participants~To identify barriers and facilitators of PrEP among study participants~Study design Prospective, open-label cohort study assessing PrEP delivery in tertiary hospital infectious diseases clinics in South Korea for 1 year~Evaluation~Baseline evaluation~HIV testing and the documentation of results are required to confirm that patients do not have HIV infection when they start taking PrEP medications. HIV Ag/anti HIV Ab combo assay should be performed before starting PrEP. Negative result of HIV Ag/anti HIV Ab combo assay within 1 week should be ascertained before PrEP initiation. Results from rapid test with oral specimen or unreliable testing results cannot be acknowledged.~Renal function with estimated creatinine clearance (eCrCl) should be evaluated before starting TDF/FTC. TDF/FTC can be prescribed for persons with eCrCl ≥60 ml/min. Any person with an eCrCl of <60 ml/min should not be prescribed PrEP with TDF/FTC.~Testing for hepatitis B virus (HBsAg, HBsAb) and hepatitis C virus (HCV Ab) should be performed before starting PrEP. Hepatitis B virus vaccination is recommended for MSM without HBsAb.~Acute HIV infection must be excluded by symptom history, physical examinations and appropriate HIV testing before PrEP is prescribed.~If HIV testing shows intermediate results, clinician should hold PrEP initiation, make efforts to identify symptoms and signs of acute viral infections, and do follow up HIV testing.~Follow up and monitoring during PrEP~All persons receiving PrEP should be seen at 1 month since PrEP initiation and at least every 3 months to assess side effects, adherence, and HIV acquisition risk behaviors.~All persons receiving PrEP should be seen at least every 3 months to assess for signs or symptoms of acute infection and repeat HIV testing (HIV Ag/anti HIV Ab combo assay). If acute infection is suspected, HIV RNA testing should be performed.~Confirmative HIV testing (western blot assay) and HIV RNA testing should be performed for persons with positive results of screening assay (HIV Ag/anti HIV Ab assay). Resistance testing should be performed for persons with confirmed HIV infection during PrEP.~If acute HIV infection is suspected during PrEP, PrEP should be stopped, combination antiretroviral therapy with TDF/FTC+boosted protease inhibitor (darunavir/ritonavir) or TDF/FTC + dolutegravir should be prescribed.~All persons receiving PrEP should be seen at least every 3 months to monitor eCrCl.~Sexually active persons receiving PrEP should be seen at least every 6 months to conduct tests for sexually transmitted infections (i.e. syphilis, gonorrhea, chlamydia).~Assessments of bone health are not routinely recommended before the initiation of PrEP or for the monitoring of persons while taking PrEP. However, assessment for bone health can be considered for any person who has a history of pathologic fractures or who has significant risk factors for osteoporosis mineral density PrEP.~All persons receiving PrEP should be seen at least 12 months to evaluate the need to continue PrEP as a component of HIV prevention considering HIV acquisition risk behavior, adherence, and so on.~Measurement Baseline data will be collected 1 months before initiation of PrEP, and the date of initiation of PrEP.~All persons receiving PrEP should be seen at 1 month since PrEP initiation and at least every 3 months to assess side effects, adherence, and HIV acquisition risk behaviors. During every visits including screening visit, below measures are assessed.~Diagnostic testing: HIV testing with a fourth generation HIV Ag/Ab test, HIV RNA assay, serologic test for syphilis using VDRL or RPR, screening for gonorrhoea and chlamydia using nucleic acid amplification test~Sociodemographics and sexual behaviors: demographic and sexual behavioral data are collected by trained interviewers using standardized questionnaires including residence, living situation, employment, insurance status, income, housing/food instability, drug use, number of anal sex partners, episodes in the past 3 months, condom use, partner HIV serostatus, sexual position, etc.

The primary objective of this study is to examine acceptability, patterns of use, rates of adherence, safety , and measured levels of drug when high risk men who have sex with men (MSM) are provided open-label tenofovir/emtricitabine (TDF/FTC) for PrEP in South Korea. Secondary objectives are 1) to evaluate HIV incidence among study participants, 2) to evaluate risk behavior and risk compensation among study participants, and 3) to identify barriers and facilitators of PrEP among study participants. The design of this study is a prospective, open-label cohort study assessing PrEP implementation in tertiary hospital infectious diseases clinics in South Korea for 1 year. Baseline data will be collected 1 months before initiation of PrEP, and the date of initiation of PrEP. All persons receiving PrEP should be seen at 1 month since PrEP initiation and at least every 3 months to assess side effects, adherence, and HIV acquisition risk behaviors. Drug concentration will be measured every 6 months. It is anticipated that approximately 100 Korean MSM will be enrolled in this study.

BACKGROUND/RATIONALE: The outbreak of coronavirus disease 2019 (COVID-19), caused by infection of SARS-CoV-2, has rapidly spread to become a worldwide pandemic. Global research focused on the understanding of the biochemical infective mechanism and on the discovery of a fast, sensitive and cheap diagnostic tool, able to discriminate the current and past SARS-CoV-2 infections from a minimal invasive biofluid. The fast diagnosis of COVID-19 is fundamental in order to limit and isolate the positive cases, decreasing with a prompt intervention the infection spreading. Moreover, the prediction of the respiratory infection severity could be of crucial importance for the fast identification and discrimination between mild clinical course, severe illness, and Acute Respiratory Distress Syndrome (ARDS). One of the first infection sites of SARS-CoV-2 is the oral cavity where the virus is able to bind and penetrate through the ACE2 receptors present on the epithelial cells of the salivary glands. Thus, a high concentration of virus particles could be found in saliva in the preliminary phases of the infection. Saliva is a complex biofluid composed of bioactive molecules that can be collected with a really minimal-invasive procedure. Raman spectroscopy is a non-invasive, fast and label-free vibrational technique, able to provide information regarding presence, concentration, environment, modifications and interactions of all the biochemical species present in a specific biofluid. Using the Raman spectroscopy, the investiators will analyze saliva collected from healthy subjects, patients affected by COVID-19 and subjects with a past infection by COVID-19. The data collected will be analyzed and used to create a Raman database able to provide a classification model based on machine learning. The possibility to monitor and characterize a potential salivary COVID-19 fingerprint could be of crucial importance for the monitoring and discrimination of COVID-19 subjects with a current and past infection from the healthy subjects.~OBJECTIVES: The aim of the project is to characterize and validate the salivary Raman fingerprint of COVID-19, understanding the principal biomolecules involved in the differences between the three experimental groups: 1) healthy subjects, 2) COVID-19 patients and 3) subjects with a past infection by COVID-19. The large amount of Raman data will be used to create a salivary Raman database, associating each data with the relative clinical data collected. The Raman database will be used for the creation of a classification model through the application of multivariate analysis in terms of principal component analysis and linear discriminant analysis. This classification model will provide a fast tool for the discrimination of the COVID-19 condition, potentially providing also information on the respiratory clinical course of the patient. The model will be translated for the application to a portable Raman spectrometer, leading to the creation of a Raman Point of Care METHODS: Starting from the preliminary results and protocols of the Laboratory of Nanomedicine and Clinical Biophotonics (LABION) - IRCCS Fondazione Don Gnocchi Milano, the saliva collected from each experimental group will be analysed using Raman spectroscopy. All the data will be processed for the baseline, shift and normalization in order to homogenize the signals collected and creating in this way the Raman database. The average spectrum calculated from each group will be characterized, identifying the principal families of biological molecules responsible for the spectral differences. Consecutively, all the spectra will be processed through multivariate analysis (principal component analysis and linear discriminant analysis) obtaining in this way the classification model. LOOCV will be used for the training of the classification model, which will be questioned using the subset validation analysis. The partial correlation coefficient (Pearson's and Spearman's correlation) will be used for the Raman correlation with the clinical parameter (e.g. COVID-19 clinical course) using as control covariates the age and sex of the subjects. The classification model will be then translated and used as point of care using a portable Raman equipped with a laser emitting at 785 nm, with a comparable spectral resolution.~SAMPLE COLLECTION: Saliva will be collected with Salivette (SARSTEDT, Germany), following the manufacturer's instructions. The cotton swab will be inserted in the subject mouth and chewed for 60 seconds. The saliva collection will be achieved through centrifugation of the swab (1000 g x 2 min), recording all the related parameters (storage temperature and the time between collection and analysis). All the collection procedures will be performed at least two hours after the last meal and teeth brushing.~SAMPLE PROCESSING: Before the analysis, saliva (3 ul) will be deposited on aluminum foil and dried overnight. The aluminum foil is fundamental to achieve the Surface Enhanced Raman Scattering, increasing the saliva Raman signal.~DATA COLLECTION: Raman spectra will be acquired using an Aramis Raman microscope (Horiba Jobin-Yvon, France) equipped with a laser light source operating at 785 nm with 100% (512mW) laser power. Acquisition time will be set at 30 seconds with double acquisition and 2 seconds delay time to prevent the formation of artifact spectra. Before each analysis, the instrument will be calibrated using the reference band of silicon. All the signals will be acquired in the region between 400 and 1600 cm-1 with a resolution of 0.8cm-1, acquiring at least 25 spectra following a square-map. The software package LabSpec 6 (Horiba Jobin-Yvon) will be used for map design and the acquisition of spectra.~DATA ANALYSIS: All the data will be fit using a fourth-degree polynomial curve to set the baseline and consecutively normalized using unit vector. The contribution of aluminum will be removed from each spectrum. The statistical analysis will be performed using the multivariate approach. Briefly, principal component analysis and linear discriminant analysis will be applied to extract the principal components and the canonical variables. These features will be used for the leave one out cross-validation (LOOCV), subset validation and correlation with the clinical parameters. Mann-Whitney will be performed on PCs scores to verify the differences statistically relevant between the analysed groups. The analysis will be performed using Origin software (OriginLab, USA)~CORRELATION: Partial correlation with Pearson's and Spearman's coefficients will be performed on the variables extracted and the clinical parameters, using as control covariates the age and sex of the subjects. Only values with p < 0.001 will be considered as statistically relevant.~TRANSLATION: The data and the classification model will be applied with a portable Raman equipped with a laser emitting at 785 nm and with a spectral resolution comparable with the one used for the previous analysis.

The outbreak of coronavirus disease 2019 (COVID-19), caused by infection of SARS-CoV-2, has rapidly spread to become a worldwide pandemic. Global research focused on the understanding of the biochemical infective mechanism and on the discovery of a fast, sensitive and cheap diagnostic tool, able to discriminate the current and past SARS-CoV-2 infections from a minimal invasive biofluid. The fast diagnosis of COVID-19 is fundamental in order to limit and isolate the positive cases, decreasing with a prompt intervention the infection spreading.~The aim of the project is to characterize and validate the salivary Raman fingerprint of COVID-19, understanding the principal biomolecules involved in the differences between the three experimental groups: 1) healthy subjects, 2) COVID-19 patients and 3) subjects with a past infection by COVID-19. The large amount of Raman data will be used to create a salivary Raman database, associating each data with the relative clinical data collected.~Starting from the preliminary results and protocols of the Laboratory of Nanomedicine and Clinical Biophotonics (LABION) - IRCCS Fondazione Don Gnocchi Milano, the saliva collected from each experimental group will be analysed using Raman spectroscopy. All the data will be processed for the baseline, shift and normalization in order to homogenize the signals collected and creating in this way the Raman database. The average spectrum calculated from each group will be characterized, identifying the principal families of biological molecules responsible for the spectral differences.~EXPECTED RESULTS: Verify the possibility to use Raman spectroscopy on saliva samples for the identification of subjects affected by COVID-19. The principal aim of the project is to create a classification model able to: discriminate COVID-19 current and past infection, identify the principal biological molecules altered in saliva during the infection, predict the clinical course of newly diagnosed COVID-19 patients, translation and application of the classification model to a portable Raman for the test of a point of care.

A prospective non-interventional study to evaluate the performance of EASYCOV IVD as point-of-care (POC) test by comparing SARS-CoV-2 positive patients with SARS-CoV-2 negative controls on paired specimens (nasopharyngeal swabs & saliva samples).~The operators performing the diagnostic tests will be blinded from the RT-PCR results (i.e. participant's group will be anonymized). Participants who have been tested by an routineTurkish MOH and FDA EUA approved RT-PCR test using nasopharyngeal swabs will be included in the study to perform the EASYCOV IVD tests in a POC setting.~Primary Objective:~• To evaluate the performance of EasyCov IVD as a point-of-care (POC) test performed on saliva samples for the diagnosis of SARS-CoV-2 infection by comparing it to a Turkish MOH and FDA EUA approved RT-PCR test performed on nasopharyngeal samples.~Secondary Objectives:~• Collection and storage of saliva samples, nasopharyngeal swabs at D0 to perform future COVID-19 related research projects and validation of future generations of EASYCOV assays as well as exploratory studies to find candidate biomarkers for Covid-19.~160 participants will be included in 1:1 ratio: 80 SARS-CoV-2 positive and 80 SARS-CoV-2 negative by a Turkish MOH and FDA approved RT-PCR IVD test

A prospective non-interventional study to evaluate the performance of EASYCOV IVD as point-of-care (POC) test by comparing SARS-CoV-2 positive patients with SARS-CoV-2 negative controls on paired specimens (nasopharyngeal swabs & saliva samples).

COVID-19 is an emergency situation which broke out from China in 2020. Health commitees and goverment set some rules and limit people's freedom to leave from their houses and it is called as 'social isolation'. With social isolation people were restricted to go outside from house and with that they had to stay at home. Staying at home and disease bring about sedentary lifestyle, anxiety and depression and changed eating habits of all person. It was very dangerous especially chronically ill persons. Physical activity and exercise are keystones for managing cardiovasculary disease risk factors. Hypertension is important risk factor all around the world. Disease control is important to prevent complications. In that study, we aimed to assess hypertensive and healhty individuals' physical activity, anxiety, healthy lifestyle habits and quality of life with changed life condition during COVID-19 social isolation.

COVID-19 is an emergency situation which broke out from China in 2020. Health commitees and goverment set some rules and limit people's freedom to leave from their houses and it is called as 'social isolation'.Staying at home and disease bring about sedentary lifestyle, anxiety and depression and changed eating habits of all person. Hypertension is an important cardiovasculary risk factor and physical activity, stress managament are very important for disease control. In that study we aimed to assess hypertensive and healthy person's anxiety level, physical activity and qualit of life level during COVID-19 social isolation.

This is a Randomized, Placebo-controlled, Double-blind, Parallel-group, Multicenter, Phase 2a Study to evaluate the Efficacy and Safety of Oral AMT-101 in Subjects with Moderate to Severe Ulcerative Colitis.

Randomized, Placebo-controlled, Double-blind, Parallel-group, Multicenter, Phase 2a Study of the Efficacy and Safety of Oral AMT-101 in Subjects with Moderate to Severe Ulcerative Colitis.

Mechanical ventilation (MV) is used to reduce work and reverse or prevent fatigue of the respiratory muscles, decrease oxygen consumption and maintain gas exchange. In addition to the benefits given to patients undergoing MV, there is a high risk of accumulating bronchial secretions, related to pathology and / or therapeutic intervention. Pulmonary hyperinflation is widespread in patients in intensive care centers (ICUs) as a bronchial hygiene therapy, being used in 40% of 64 Australian ICUs as demonstrated by Dennis et al., Through contact with physical therapists. Mechanical hyperinflation associated with tracheal aspiration is able to increase the amount of secretion aspirated when compared to isolated aspiration in patients undergoing mechanical ventilation.~To evaluate whether the use of the pulmonary hyperinflation maneuver in the mechanical ventilator is hemodynamically stable through the collection in two moments of the heart rate (HR), mean arterial pressure (MAP), peripheral saturation (SpO2), respiratory rate (RF) variables that will be analyzed from the postoperative unit's multiparametric monitor.~Evaluate the change in respiratory mechanics through collection in two moments after the mechanical hyperinflation technique through dynamic compliance (Cdyn), tidal air volume (VAC), peak pressure (Ppico). The population will consist of patients from the Post-Operative Unit (UPO), unit intensive care (UCI) and emergency room, from the Institute of Cardiology, of both sexes, over 18 years old, mechanically ventilated more than 48 hours and the sample consisting of 50 individuals. These will be submitted to the use of the pulmonary hyperinflation maneuver in the mechanical ventilator.~This is a randomized crossover clinical trial in which the individuals selected for the study will be randomized to receive isolated tracheal aspiration (Control Group) and pulmonary hyperinflation through the mechanical ventilator associated with tracheal aspiration (Intervention Group). Randomization will be performed through the randomization.com website by a 1: 1 crossed block, allocating the patient to one of the groups and, after 24 hours, another technique will be performed. In addition, a control aspiration will be performed 2 hours before both techniques.~For basal aspiration, the patient will be placed in the supine position with the head elevated at 30º, will be submitted to a single aspiration with a size 12 probe (Mark Med), with a vacuum adjusted to -40cmH2O of pressure, with basic asepsis care being maintained for performing the technique35.~In the control group, patients will be ventilated for 1 minute with 100% inspired oxygen (FiO2), followed by three aspirations for 15 seconds and with an interval of 30 seconds.~In the participants of the intervention group, the calculation of the ideal tidal volume for each patient will be performed, after which they will be positioned in the supine position, the head elevated to 30º in assisted pressure-controlled ventilation mode, increasing 10 cmH2O in inspiratory pressure and, in assisted ventilation mode. controlled by volume, we will increase 50% of the tidal volume for a period of 10 minutes, observing the Ppeak that cannot exceed 40 cmH2O and the drive pressure that cannot exceed 15 cmH2O in both ventilation modes, and then a new aspiration will be performed. in the same way as the control group. The hemodynamics data will be taken from the multiparametric monitor of the hospitalization units (philips) and the respiratory mechanics data will be collected from the mechanical ventilator screen (Servo S; Drager; Newport), before and after the techniques. The volume of secretion will be stored in the collection flask (Water Seal 120 ml) and weighed using a high precision scale, discounting the weight of the collection flask.~The Informed Consent Form (ICF) will be signed by the responsible family member, containing information and explanations about the present study and the researcher will be available to explain doubts and questions at the time and afterwards through the telephone present at the ICF. All procedures will be performed under the supervision of the physiotherapist at the hospital. It is understood that this research may offer a minimal risk to volunteers, according to resolution 466/12 of the National Health Council, since they may have some discomfort and / or their hemodynamic situation altered by the application of the aforementioned physical therapy technique. As a counterpart, in case the predicted risk occurs, the subjects will receive all the necessary care from the researcher, together with the unit's physiotherapist and medical team, if necessary. The benefits to the subjects refer to the possibility of improving their respiratory function and bronchial hygiene.

Mechanical ventilation (MV) is used to reduce work and reverse or prevent fatigue of the respiratory muscles, decrease oxygen consumption and maintain gas exchange. In addition to the benefits given to patients undergoing MV, there is a high risk of accumulating bronchial secretions, related to pathology and / or therapeutic intervention. Pulmonary hyperinflation is widespread in patients in intensive care centers (ICUs) as a bronchial hygiene therapy, being used in 40% of 64 Australian ICUs as demonstrated by Dennis et al., Through contact with physical therapists. Mechanical hyperinflation associated with tracheal aspiration is able to increase the amount of secretion aspirated when compared to isolated aspiration in patients undergoing mechanical ventilation. To assess whether the pulmonary hyperinflation maneuver with the mechanical ventilator, compared to isolated tracheal aspiration, increases the removal of secretions. To evaluate whether the use of the pulmonary hyperinflation maneuver in the mechanical ventilator is hemodynamically stable through the collection in two moments of the variables of heart rate (HR), mean arterial pressure (MAP), peripheral saturation (SpO2), respiratory rate (RF) that will be analyzed from the postoperative unit's multiparametric monitor.~Evaluate the change in respiratory mechanics through collection in two moments after the mechanical hyperinflation technique through dynamic compliance (Cdyn), tidal air volume (VAC), peak pressure (Ppico). The population will consist of patients from the Post-Operative Unit (UPO), from the Institute of Cardiology, of both sexes, over 18 years old, mechanically ventilated and the sample consisting of 50 individuals. These will be submitted to the use of the pulmonary hyperinflation maneuver in the mechanical ventilator. Randomized crossover clinical trial.

Paragangliomas (PGL) are rare neuroendocrine tumors inherited in 40% of cases. SDHx genes (SDHA, SDHB, SDHC, SDHD), encoding the 4 subunits of the mitochondrial enzyme succinate dehydrogenase (SDH), are the most frequently involved.~Accumulation of succinate, the substrate for SDH, is a very specific biomarker for these mutations. Recently, we have demonstrated the feasability of detecting and quantifying succinate in tumors in vivo, by magnetic resonance spectroscopy (1H-SRM).~Patients carrying these mutations frequently develop cervical PGL for which the treatment of choice is external beam radiation therapy (EBR).~The objective of this project is to determine the feasibility of using 1H-SRM for the evaluation of early response to EBR therapy in patients with cervical SDHx PGL.

Qualitative and quantitative biomarker of response to radiotherapy is needed in paragangliomas. We aim at assessing the added value of 1H-SRM for the evaluation of early response to EBR therapy in patients with cervical SDHx PGL.

Objectives:~Aim 1. The investigation will identify the specific tissue compartment distribution of immunoglobulin E (IgE) expression within human nasal polyps. Colocalization studies will examine functional interaction of IgE with effector cells.~Aim 2. The investigation will examine the direct effect of omalizumab on expression of Type 2, 1, and 3 inflammatory pathways in human nasal polyp tissue from phenotypically characterized chronic rhinosinusitis with nasal polyposis (CRSwNP) patients.~Study Rationale: Human nasal polyps express high local tissue IgE. However, the tissue distribution, cellular location and functional consequence of IgE accumulation within the polyp tissue is not known. Phase 3 studies of omalizumab demonstrated efficacy, with responders. However, the reason for non-responder outcomes in a subset of CRSwNP patients was not understood. Therefore, the goal of this study is to examine the mechanism of action of omalizumab in CRSwNP, such that specific responders for this treatment can be identified and therapy can be optimally directed.

The goal of this study is to examine the mechanism of action of omalizumab in ex vivo tissue culture of whole human nasal polyps from patients with chronic rhino sinusitis with nasal polyposis (CRSwNP), such that specific molecular markers of inflammation can be identified.

Coronaviruses are a group of viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can be mild, such as some cases of the common cold, and others that can be lethal, such as severe acute respiratory syndrome (SARS), (middle east respiratory syndrome) MERS, and COVID-19. They contain a positive-sense, single-stranded RNA genome. The genome size ranges from approximately 27 to 34 kilobases. It has a 5' methylated cap 5'leader, UTR, replicas/transcriptase enzyme, spike (S) protein, envelope (E) protein, membrane (M) protein, nucleocapsid (N) protein, 3'untranslated region (3'UTR), and a poly (A) tail, respectively. The S protein has a major role in eliciting the protective immunity during infection with SARS-corona virus (SARS-CoV) by inducing neutralizing-antibodies and T-cell responses. It is also the most mutated part of the coronavirus genome. The aim of this effort is to study host-pathogen interaction in Egyptian patients infected with COVID-19. The investigators will perform genome-wide miRNA and transcriptome screens in the infected patients along with healthy ones for comparison. All types of cytokines play pivotal roles in immunity, including the responses to different viral infections. Therefore, The investigators will study the cytokines profile in response to that infection. By comparing miRNA and transcriptome screens along with cytokines profiles, an important molecule might be identified, which could play role in the inhibition of the COVID-19 outbreak. In addition, this information will help us gaining awareness of the immune process and knowing about the genes involved in the immune response against COVID-19 with an emphasis on the expression of cytokines.

The aim of this effort is to study host-pathogen interaction in Egyptian patients infected with COVID-19. The investigators will perform genome-wide miRNA and transcriptome screens in the infected patients along with healthy ones for comparison. All types of cytokines play pivotal roles in immunity, including the responses to different viral infections. Therefore, The investigators will study the cytokines profile in response to that infection. By comparing miRNA and transcriptome screens along with cytokines profiles, an important molecule might be identified that could play role in the inhibition of the COVID-19 outbreak. In addition, this information will help us gaining awareness of the immune process and knowing about the genes involved in the immune response against COVID-19 with an emphasis on the expression of cytokines.

n-3 polyunsaturated fatty acids, conjugated-linoleic acids and conjugated-linolenic acids show interesting effects in the context of health. Indeed, some studies suggest positive effects on circulating lipids or inflammation associated with certain disorders such as diabetes, following the consumption of these fatty acids.~However, these fatty acids are not very present in the classic diet. Therefore, we have developped hens eggs naturally enriched in n-3 polyunsaturated fatty acids, conjugated-linoleic acids and conjugated-linolenic acids by changing the hens feed.~This study has two objectives: 1) to check that the daily consumption of two eggs with a particular fatty acid pattern rich in n-3 polyunsaturated fatty acids (α-linolenic acid, docosahexaenoic acid), conjugated-linoleic acid and conjugated-linolenic acid is well tolerated by the consumer ; 2) to evaluate the effects of the consumption of these eggs on health parameters in subjects presenting a risk of developing a metabolic disorder.~To do this, 80 subjects aged 35 to 75, sedentary (<2 hours of physical activity per week) and with abdominal obesity (> 94cm for men and> 80cm for women) were recruited and were divided into two groups: the control group (12 subjects consuming 2 classic eggs for 3 months per day) or the test group (12 subjects consuming 2 eggs enriched in omega per day for 3 months).~A medical examination with blood sampling was scheduled every month at baseline (Day 0), after one month (Day 30), after two months (Day 60) and at the end of the 3 months of intervention (Day90). During those visits, the following were monitored: glucose parameters, lipids parameters, fatty acid profile of red blood cells and plasma and safety parameters related to haematology, kidney and liver functions .~During these monthly medical visits patients also completed the questionnaires assessing intestinal tolerance (visual analogue scale showing 10 gastrointestinal symptoms), satiety (visual analog scale questionnaire) and well-being (36 items short form survey). Eating habits were monitored using a food diary. Additional parameters were measured only during the first and the last visit: coagulation, nutritional status, endothelial function and inflammation.

This study has two objectives: 1) to check that the daily consumption of two eggs with a particular fatty acid pattern rich in n-3 polyunsaturated fatty acids (α-linolenic acid, docosahexaenoic acid), conjugated-linoleic acid and conjugated-linolenic acid is well tolerated by the consumer ; 2) to evaluate the effects of the consumption of these eggs on health parameters in subjects presenting a risk of developing a metabolic disorder.~This monocentric study is an interventional, randomized, double-blind, control study.

The objective of the study is to assess the utility of ECG Belt to understand the conduction and ECG characteristics of LBBP and HOT-CRT and compare with preexisting data in traditional CRT and RVP.~Specific Objective:~To demonstrate and establish electrical resynchronization using ECG Belt Research System in Left Bundle Branch Pacing (LBBP) and HOT-CRT.~To assess ECG Belt derived native conduction parameters and compare them to LBBP and HOT-CRT.~To compare with historic ECG belt parameters obtained for right ventricular pacing/ Biventricular pacing in prior studies.~The ECG Belt study is a prospective, single-center, investigational, pre-market research study. The study team will identify all patients who satisfy the inclusion and exclusion criteria. The study team will evaluate the ECG Belt Research System to assess the electrical characteristics of conduction system pacing in patients with preexisting LBBP or HOT-CRT.~Eligible patients would have successfully undergone LBBP using Medtronic 3830 lead. LBBP will be confirmed at implant using left bundle potentials recorded from the lead, ECG morphology during unipolar and bipolar pacing, peak LV activation time and lead depth in the LV septum by contrast at implant and 2D echo post-implant.~ECG belt would be used to record ECG during baseline rhythm, LBBP in unipolar and bipolar configurations and / or during HOT-CRT using His-Bundle Pacing (HBP) or LBBP. These ECG belt characteristics would then be compared with baseline and existing data on Right Ventricular RV pacing and traditional Biventricular pacing.

The objective of the study is to assess the utility of ECG Belt to understand the conduction and ECG characteristics of Left Bundle Branch Pacing (LBBAP) and His-Optimized Cardiac Resynchronization Therapy (HOT-CRT) and compare with preexisting data in traditional Cardiac Resynchronization Therapy (CRT) and Right Ventricular Pacing (RVP).

Through a high-quality, single-blind, three-arm mixed-method pilot feasibility study using randomized treatment assignment, the study team will assess two new innovative interventions, Sahaj Samadhi Meditation (SSM) and Health Enhancement Program (HEP), both delivered virtually, to augment clinical care of patients with irreversible age-related vision loss (IARVL), with the goal of enhancing mental health and quality of life (QOL) for patients and/or their caregivers. Participants will be blinded to the treatment hypothesis, while investigators and treating clinicians will be additionally blinded to the intervention. Both SSM and HEP will be taught over 4 consecutive days in similar sized groups (10 patients and/or their 10 caregivers) followed by weekly reinforcement sessions for subsequent 11 weeks. Self-rated questionnaires will be used to collect data on quality of life and mental health symptoms at 0-week and 12-week follow-up

Vision loss is common among older adults and leads to an increased risk for depression and difficulties in daily tasks, thus requiring dependence on caregivers. This study will assess the feasibility of providing two virtual interventions, Sahaj Samadhi Meditation (SSM) and Health Enhancement Program (HEP), to supplement care of patients with irreversible age-related vision loss (IARVL) and their caregivers, with the goal of enhancing mental health and quality of life.

A 24-month randomized, single-blind, placebo-controlled trial to investigate the efficacy of empagliflozin to reduce atrial fibrillation burden in patients with diabetes mellitus or overweight, heart failure and atrial fibrillation in which a rhythm control strategy is indicated.

The primary purpose of this trial is to evaluate the impact of empagliflozin, as compared with placebo, in patients with diabetes mellitus or overweight, heart failure and atrial fibrillation.

Gestational diabetes mellitus (GDM) poses a substantial long-term health burden to women due to the 7-fold increased risk of developing type 2 diabetes mellitus (T2DM) and other cardiovascular disorders. Yet, there are many gaps in the transition period after GDM, which is a particularly critical time due to enhanced motivation and access. Nevertheless, a minority of women receive postpartum screening for dysglycemia or have successful transition to primary care. Although T2DM prevention interventions can be successful, they cannot be deployed without retention and engagement in care. Addressing the unique barriers experienced by postpartum women requires innovative models of health care delivery to promote prevention of T2DM after GDM. One potential intervention with demonstrated successes in other arenas is patient navigation, a barrier-focused, longitudinal, patient-centered intervention that offers support for a defined set of health services.~This protocol is to perform a pilot assessment of Sustaining Women's Engagement and Enabling Transitions after GDM (SWEET), a GDM-focused intervention that will apply barrier-reduction patient navigation strategies to improve health after a pregnancy with GDM. The investigators aim to determine, via a randomized controlled trial of 40 women who have had GDM, whether those who receive the SWEET navigation intervention have improved diabetes-related health at 1 year after birth compared to those who receive usual care. In order to promote self-efficacy, enhance access, and sustain long-term engagement, the SWEET intervention will provide GDM-specific, individualized navigation services that leverage existing clinical infrastructure, including logistical support, psychosocial support, and health education, through 1-year postpartum.~Aim 1 will evaluate whether clinical (weight, glycemic control, abdominal circumference, and blood pressure), health services (postpartum and primary care visit attendance), and patient-reported (diabetes self-efficacy, activation, and T2DM risk perception) outcomes differ in women exposed to SWEET versus usual care. Aim 2 will evaluate feasibility and acceptability. This proposal will generate key data for the conduct of a full-scale trial of a GDM-specific postpartum patient navigation program that will address critical questions about long-term maternal health and T2DM prevention.~SWEET bridges the chasm between care during pregnancy - focused on improving the health of the pregnant woman and her offspring - and long-term women's health care - focused on chronic disease management and preventive health. The long-term goals are to understand how to optimize long-term health after GDM in order to prevent or ameliorate the effects of T2DM beyond the perinatal period.

This study is a pilot assessment of Sustaining Women's Engagement and Enabling Transitions after GDM (SWEET), a GDM-focused intervention that will apply barrier-reduction patient navigation strategies to improve health after a pregnancy with gestational diabetes mellitus. The investigators aim to determine, via a randomized controlled trial of 40 women who have had GDM, whether those who receive the navigation intervention have improved diabetes-related health at 1 year after birth compared to those who receive usual care. The SWEET intervention will provide GDM-specific, individualized navigation services that leverage existing clinical infrastructure, including logistical support, psychosocial support, and health education, through 1-year postpartum. Participants will undergo surveys, interviews, and medical record review at multiple time points. The investigators will also conduct qualitative interviews with clinical providers.

Intellectual disability and neurobehavioural comorbidities affect at least 50% of the individuals with Duchenne muscular dystrophy (DMD), which, although a rare genetic disease, is the most common form of muscular dystrophy in childhood. Several studies have documented that 25% of the DMD population has intellectual disability with recent studies suggesting that autism and clinically relevant hyperactivity affects 20% and 25% of DMD boys respectively. A milder allelic variant, named Becker muscular dystrophy (BMD), has similar prevalence in the population and is also associated with variable degrees of central nervous system (CNS) comorbidities, which however have been less well defined.~The investigators will address these deficiencies in a large multicentre study funded by the European Commission (EU H2020) involving 6 countries (Denmark; The Netherlands; France; Spain; Italy and UK) with the largest European neuromuscular centres and advocacy groups. The aim will be to study the neurobehavioural aspects of DMD and BMD as well as their correlation to the genotype. This study will involve male participants with DMD aged 5-17 years and with BMD aged 5-50 years. It will comprise of online questionnaires that will be completed either by a parent of a participant <17 years or an adult participant. The questionnaires take approximately 70 minutes to complete, however this can be done in multiple sittings. Currently there is a lack of information to assist the prognosis of CNS comorbidities, as existing databases and registries typically focus on the motor milestones and physical disability of these patients. There is therefore, an urgent need to present the course and outcomes in DMD and BMD patients with a wide range of DMD mutations, to provide information at the point of diagnosis and onwards for families, clinicians and service providers. It will also assist in paving the way to greater biological understanding and personalization of interventions.

The objective of this study is to collect data from a large cohort of individuals with DMD and BMD focusing on the neurobehavioural aspects of these conditions and their correlation to the location of the DMD gene mutation.

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.~The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.~One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.~The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained.~The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8. The key secondary objectives are 1) to evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29.~Contacts:~20-0013 Central Contact~Telephone: 1 (301) 7617948~Email: [email protected]

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.~The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.~One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.~The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.~The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.~One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.~The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained.~The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8. The key secondary objectives are to 1) evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29.~Contacts:~20-0013 Central Contact~Telephone: 1 (301) 7617948~Email: [email protected]

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.~The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.~One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.~The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

Introduction: Stress is a natural phenomenon within the human body that prepares the organism for action. However, due to the current life and work habits and demands, stress goes beyond what is beneficial and starts to suppose a burden. Nowadays, work stress, which is defined as a harmful reaction, which people have to deal with, to the pressures and undue demands placed on them at work, has gained importance as it affects both health and productivity of workers. If stress persists over time, it can lead to the syndrome known as Burnout, which implies deep exhaustion, and inefficiency. In the last years, different wearable devices have started to be used to monitor stress at work with the aim of understanding their consequences on physical activity and sleep quality.~Objective: To establish whether wearable wristbands are devices capable of determining the work stress level of workers from a research center in Galicia. To this end, it will be determined the work stress level and quality of life of these workers to conclude if the devices measure the work stress with precision. Also, different physical activity, sleep and occupational functioning patterns will be identified to study the relation between them and the work stress level and quality of life.~Methods and Analysis: The study will be carried out with workers from a research center from Galicia, being this the only inclusion criterion. As for exclusion criteria, workers will not be allowed to participate if they are expected to retire in a period of 5 years or less, have significant health issues that hinder the participation in the study, or present skin hypersensitivity or allergic reactions caused by the materials the wristbands are made of.~This is a pilot study to determine the viability, sample size, cost, and duration of the study. Likewise, a pilot project has also been designed in this study in order to demonstrate that the planned measurements, the data collection instruments and the data management system are feasible and effective. This is an observational, analytical, and longitudinal study. That is, in this study different variables of the population under study will be observed and recorded without intervention and with the aim of establishing causal associations between variables. It is considered longitudinal because variables will be followed for 6 months, continuously recording and monitoring physical activity and the quality of sleep (wristbands), and in a specific way, variables related to work stress, quality of life, and perception of the quality of sleep and the level of physical activity (specific evaluation tools).~As for the statistical analysis, and once the data are preprocessed, for the collected variables the Kolmogorov-Smirnov will be applied to check if they behave as a normal distribution. Otherwise, posterior analysis with non-parametric tests will be performed. The correlation of the numeric variables will be analysed through the Pearson or Spearman's Rho correlation depending on the sample distribution. A Chi-Square test will be used to assess the association between categoric variables unless the observed frequencies are <5%, for which a likelihood ratio test would be used. Regarding the association between quantitative and qualitative variables, the mean comparison with a T and ANOVA test, or a Mann Whitney and Kruskal Wallis test, as appropriate, will be performed. To finish, with the aim of determining whether there are significant differences between the results of the beginning, mid-term and final evaluations, a Wilcoxon test will be applied.

Introduction: Work stress has become more and more important in the last years as it affects both health and productivity of workers. In the last years, different wearables devices have started to be used to monitor stress at work to understand their consequences on daily life activity and sleep quality.~Objective: to establish whether wearable wristbands are devices capable of determining the work stress level of workers from a research center in Galicia, for which different variables related to the work stress level and quality of life of these workers will be evaluated.~Methods and analysis: The only inclusion criterion is to be a worker from a research center from Galicia. As for exclusion criteria, will not be allowed to participate those workers who are close to retirement ( <5 years), have health issues that hinder participation in the study, or present skin hypersensitivity or allergic reactions due to the materials the wristbands are made.~This is a pilot study to determine the viability, sample size, cost, and duration of the study. This is an observational, analytic, and longitudinal study. In other words, in this study different variables from the population of interest will be observed and recorded without any direct intervention, so as to establish causality associations between these variables. It is considered as longitudinal since a six-months tracking of the variables will be performed.~As for the statistical analysis, different tests will be performed to analyse the distribution, correlation, and association of the different features, as well as the significant differences between them at different points of the study (detailed below).

Chronic urticaria affects up to 1% of the population. Rarely, chronic urticaria may be refractory to updosing four-fold antihistamine drugs and then can be improved with subcutaneous OMALIZUMAB. OMALIZUMAB is available for chronic urticaria since 2015. It is an IgG1 monoclonal antibody targeting IgE and administrated every 4 weeks which represent a cost of nearly 800€/month excluding nurse fees. Efficacy and good tolerance have already been demonstrated in real-life large cohorts of patients. A 6 months treatment duration is proposed before evaluating the efficacy and discontinuating the treatment in the absence of adequate response. Mean duration of chronic urticaria is 3 to 5 yearss with high standard deviations. Therefore, optimal duration of treatment with OMALIZUMAB is unknown and discontinuation modalities differ between physicians.~The aim of this study is to evaluate the mean duration between initiation and first discontinuation of OMALIZUMAB in patients treated for chronic urticaria and explore the different factors influencing this duration and its outcome.~To accomplish this, the investigators will conduct a restrospective analyse of all patients treated with OMALIZUMAB for chronic urticaria from 2010 to 2020 in the major French hospital reference centers for chronic urticaria management : Paris, Lyon, Grenoble, Lille, Bordeaux, Nantes, Rouen, Saint-Etienne, Montpellier.

Chronic urticaria affects up to 1% of the population. Chronic urticaria refractory to updosing antihistamines can benefit from OMALIZUMAB, which is an anti-IgE IgG1 monoclonal antibody administrated every 4 weeks subcutaneously which represents a cost of nearly 800€/month excluding nurse fees. Efficacy and good tolerance have already been demonstrated in real-life large cohorts of patients. A 6 months treatment duration is proposed before evaluating the efficacy and discontinuating the treatment in the absence of adequate response. Mean duration of chronic urticaria is 3 to 5 years with high standard deviations. Therefore, optimal duration of treatment with OMALIZUMAB is unknown and discontinuation modalities differ between physicians.~The aim of this study is to evaluate the mean duration between initiation and first discontinuation of OMALIZUMAB in patients treated for chronic urticaria and explore the different factors influencing this duration and its outcome.

Bedside echocardiography plays a critical diagnostic role in patients with heart failure, being other examinations (i.e., physical examination, electrocardiogram, and chest radiograph) unable to provide key information to discriminate between diastolic and systolic heart failure. Transthoracic echocardiography (TTE) can assess diastolic function by means of the doppler filling pattern, and can non-invasively measure intracardiac pressure at the bedside.~During sinus rhythm, diastolic flow shows the E and A waves, which reflects early diastolic filling and atrial contraction in the late diastole, respectively. Velocity of blood flow across the mitral valve depends on the trans-mitral pressure gradient; then, E-wave velocity is influenced both by the rate of early diastolic relaxation and by the left atrial pressure. Changes of the velocity pattern can suggest left ventricular diastolic function (LVDD) and prognosis, although mitral inflow patterns are highly susceptible to loading conditions (mainly left atrial pressure). LVDD is quite is a condition quite common in the population. A cross-sectional survey of over 2000 randomly selected Minnesota residents aged 45 years or older found an incidence of LVDD almost five times higher than LV systolic dysfunction (28% vs. 6%, respectively), which was a strong predictor of mortality (hazard ratio ranging from 8.3 for mild LVDD to 10.2 for at-least-moderate LVDD).~In a randomly recruited population sample (n = 539; 50.5% women; mean age, 52.5 years), the prevalence of the LVDD in those patients older than 50 y.o. was of about 50%5.~Doppler echocardiography could be a noninvasive tool for the detection of weaning-induced left ventricular filling pressure elevation. Transmitral flow can help measure peak Doppler velocities of E and A waves. E/A ratio has been proposed to estimate the left ventricular filling pressure. Tissue Doppler imaging can measure early diastolic mitral annular velocity (E'), which is a load-independent indicator of myocardial relaxation. The combination of tissue Doppler imaging and pulsed Doppler transmitral flow can allow the computation of the E/E' ratio, which is one of the best echocardiographic estimate of left ventricular filling pressure.~The role of LVDD in critically ill patients is probably greatly underestimated by intensivists, probably because in the past diastolic function was difficult to evaluate at the bedside6. The LVDD in intensive care unit (ICU) patients can affect the outcome of weaning from mechanical ventilation, especially in septic patients. In fact, cardiogenic pulmonary edema has been recognized as a highly incident cause of weaning failure. Unsuccessful weaning from mechanical ventilation occurs in approximately 20% of patients and is related to prolonged mechanical ventilation, length of stay in the intensive care unit, and increased morbidity and mortality. It has been proved that a spontaneous breathing trial (SBT) increases the left ventricular filling pressure, leading to cardiogenic pulmonary edema and impaired gas exchange.~However, studies focused on the impact of that medical condition on weaning showed conflicting results. Moreover, heterogeneous definitions and measurements of LVDD have been provided, associated to different form of SBTs. Furthermore, the majority carried out a cross-sectional assessment of the LVDD before and after the SBT, not including changes in the diastolic function during the ICU stay. All these variables limit the comparability and the clinical applications of these studies.~Moreover, LV diastolic function depends on myocardial relaxation, LV stiffness, and filling pressures, which are frequently impaired during the ICU stay (e.g., progression of the disease, volume resuscitation, positive end-expiratory pressure, administration of inotropes, vasopressors, etc). It is still uncertain whether the SBT failure could be affected by pre-existing conditions (i.e. a LVDD present at the ICU admission) or by a worsening of the cardiac function after the ICU admission.~As a matter of fact, the assessment of LVDD at the bedside is not routinely performed before the SBT and the role of the degree of the LVDD in still not defined. Moreover, it unclear whether the outcome of the weaning process could be affected by a pre-existing LVDD (before ICU admission), or by the worsening of a chronic pattern, or by a de-novo LVDD presentation.

The role of the left ventricular diastolic function (LVDD) in the weaning failure from mechanical ventilation in unclear. Specifically, is unclear whether the outcome of the weaning process could be affected by a pre-existing LVDD (before ICU admission), or by the worsening of a chronic pattern, or by a de-novo LVDD presentation.

Background: The coronavirus disease 2019 (COVID-19) became pandemic after emerging in Wuhan, China, in December 2019 which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). Following the swift spread of the virus,4, 710,000 confirmed cases and 315,000 deaths were reported worldwide as of May 17, 2020,and 317 confirmed cases and 5 deaths are reported nationally. To understand the drastically negative impacts of COVID-19 on the public health and key features pertinent to the disease various researches are under investigation at the global level and they are contributing to delineating the characteristics of the disease and its lethality. However, the potential acceptability of different risks varies depending on numerous factors including the type of research and the context in which it takes place. Currently, it is recognized that a 'one size fits all' approach towards the design and implementation of interventions may not be appropriate. Therefore, it is found apparent that global priorities, protocols and intervention assessments have to be contextualized and adjusted to local needs and realities, including translation of results.~Objective: To determine the epidemiological and clinical features of COVID-19 cases, immunological and virological courses, interaction with nutritional status, and response to treatment for COVID-19 patients admitted to treatment centers in Ethiopia.~Methods: This multi-site cohort enrolls, patients with confirmed COVID-19 infection admitted to treatment centers will be enrolled irrespective of their symptoms and followed up for 12 months. Baseline epidemiological, clinical, laboratory and imaging data will be collected from treatment records, interviews, physical measurements and biological samples. Endline data involves treatment and prognostic outcomes to be measured using different biomarkers and clinical parameters, The patients will be followed up in the selected treatment centers for COVID-19 infection. For all data collected both descriptive and multivariable analyses will be performed to isolated determinants of the treatment outcome and prognosis to generate relevant information for informed prevention and case management.~Expected outcome: The study will generate scientific data for a systematic understanding of natural history, epidemiological characteristics, clinical features and management of COVID-19 that will in turn enables country's health sector to develop strategies to prevent and control the pandemic before it poses further health and socioeconomic crisis.

The aim of the study will be to determine the epidemiological and clinical features of COVID-19 cases, immunological and virological courses, interaction with nutritional status, and response to treatment for COVID-19 patients admitted to treatment centers in Ethiopia.~Methods: This multi-site cohort enrolls, patients with confirmed COVID-19 infection admitted to treatment centers will be enrolled irrespective of their symptoms and followed up for 12 months. Baseline epidemiological, clinical, laboratory and imaging data will be collected from treatment records, interviews, physical measurements and biological samples. Endline data involves treatment and prognostic outcomes to be measured using different biomarkers and clinical parameters, The patients will be followed up in the selected treatment centers for COVID-19 infection. For all data collected both descriptive and multivariable analyses will be performed to isolated determinants of the treatment outcome and prognosis to generate relevant information for informed prevention and case management.

Pre-hospital factors associated with poor neurologic outcome are well known. Meanwhile, in-ICU factors for the first 24 hours may impact neurologic outcome.~This observational study aim to study the factors such as ECLS, NSE dosage, therapeutic hypotermia... and their association with neurologic outcome in patient with myocardial infarction due to instable coronaropathy complicated by an out-of-+hospital cardiac arrest.~This is designed to be a observationnal, prospective, multicentric national french study

This study evaluate the association of some in-ICU factors with the neurological prognosis of patients admitted for an out-of-hospital cardiac arrest due to a myocardial infarction.

Despite high risks of readmission and complex medical needs, there are no transitional care standards in the U.S. for patients with moderate-to-severe traumatic brain injury (TBI). Patients with moderate-to-severe TBI (age < 65 years) discharged home from acute hospital care without inpatient rehabilitation have cognitive, physical, behavioral, and emotional impairments that affect their abilities to independently self-manage their health, wellness, and activities of daily living. Activity limitations often result in increased family involvement for managing the person's care. The complexity of needs combined with the fragmentation of healthcare services creates the perfect storm for mismanaged symptoms, adverse health events, readmissions, and a lower likelihood of return to work and school. Transitional care is defined as actions in the clinical encounter designed to ensure the coordination and continuity of healthcare for patients transferring between different locations or levels of care in close geographic proximity. In other patient groups who experience acute events (e.g., stroke, myocardial infarction), transitional care management has led to improved patient and family outcomes. Although preliminary research shows that patients with TBI and families desire and could benefit from interventions to support the transition from acute hospital care to home, the strength of evidence on this topic is low. TBI transitional care interventions developed to date are ineffective in improving functional outcomes and do not incorporate family needs. Thus, the purpose of our study is to first develop and refine a patient- and family-centered TBI transitional care intervention to support patients with moderate-to-severe TBI and their family caregivers during the transition home from acute hospital care. The intervention will aim to improve quality of life for patients with TBI, reduce strain for their family caregivers, and direct patients and families to appropriate resources and care that is concordant with their health-related goals. Second, we will examine the feasibility and acceptability and assess the preliminary efficacy of the TBI transitional care intervention. The primary outcome will be patient quality of life at 16 weeks post-discharge. This study will also examine secondary outcomes at 16 weeks post-discharge, including family caregiver strain and preparedness for the caregiving role, and patient and family caregiver self-efficacy and healthcare utilization. The new knowledge generated from the proposed research will guide the research team in designing and conducting an NIH R01 implementation-effectiveness clinical trial of the TBI transitional care intervention and will ultimately enhance the standard of care for patients with TBI discharged home from acute hospital care and families

Despite high risks of readmission and complex medical needs, there are no transitional care standards in the U.S. for patients with moderate-to-severe traumatic brain injury (TBI) discharged home from acute hospital care without inpatient rehabilitation. To enhance the standard of TBI care, we will develop and refine a patient- and family-centered TBI transitional care intervention that addresses specific needs and preferences for patients with TBI (age < 65 years) and families and will assess the feasibility, acceptability, and preliminary efficacy of the intervention.

Since the end of 2019, an epidemic of SARS-CoV-2 infections (COVID-19) began in China and is now a global pandemic affecting more than 3 millions of people. Droplets and close contact are the most common routes of transmission of SARS-CoV-2 and aerosol transmission may be another route. Researchers have detected SARS-CoV-2 in samples of respiratory tract, saliva, stool, gastrointestinal tract, urine, tears and conjunctival secretions of COVID-19 patients.~Vertical transmission from mother to infant has been suspected, but not confirmed to date. Information about localization of SARS-CoV-2 in the genital tract or shedding is poorly documented and the results of these studies were discrepant. One of two studies have reported SARS-CoV-2 RNA in semen from six infected patients. However, there is no data on the duration of the seminal excretion of the virus, its viral load and infectiousness and on its localization in semen compartments (cells, seminal plasma, spermatozoa).~The purpose of this study is to seek the presence of SARS-CoV-2 in semen, to determine its localization and infectiousness and to assess the efficiency of spermatozoa processing methods to obtain virus free spermatozoa.~This is a prospective study involving 50 patients, with acute SARS-CoV-2 infection and a positive RNA detection. Men will give semen, saliva, urine and blood specimens following RT-PCR diagnosis and 15, 30, 60 and 90 days after. SARS-CoV-2 RNA will be detected in seminal plasma, native semen cells and processed spermatozoa.

This is a prospective study involving 50 patients, with acute SARS-CoV-2 infection and a positive RNA detection. Men will give semen, saliva, urine and blood specimens following RT-PCR diagnosis and 15, 30, 60 and 90 days after. SARS-CoV-2 RNA will be detected in seminal plasma, native semen cells and processed spermatozoa.~The purpose of this study is to seek the presence of SARS-CoV-2 in semen, to determine its localization and infectiousness and to assess the efficiency of spermatozoa processing methods to obtain virus free spermatozoa.

This is a multisite longitudinal study of the long-term lung health impact of COVID-19 using hyperpolarized xenon-129 (129Xe) magnetic resonance imaging (MRI) over a period of up to 4 years.~In total 200 participants age ≥ 18 and <80 years who experienced a documented case of COVID-19 (documented by positive COVID-19 test and/or clinical history) will be screened and recruited if they meet all inclusion criteria at the 5 participating sites. Participants will be grouped in mild or severe COVID-19 infection (100 in each group) including 50 with symptoms and at least 50 participants who were hospitalized with COVID-19 infection, all of whom are within 3 months post recovery and non-infectious. Participants will attend up to 5 study visits over the 4 year period. (Visit 1 within 3 months post-COVID-19 recovery, Visit 2 at 24 ± 4 weeks, Visit 3 at 48 ± 4 weeks, Visit 4 at 78 ± 4 weeks, Visit 5 at 200 ± 16 weeks)~At all visits, participants will complete 129Xe MRI, questionnaires (St. George's Respiratory Questionnaire, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Modified Borg Scale Breathlessness and Fatigue Questionnaire, Baseline Dyspnea Index Questionnaire and International Physical Activity Questionnaire), pulmonary function tests (Spirometry, Plethysmography, Forced Oscillation Technique, Fractional Exhaled Nitric Oxide, and Multiple Breath Nitrogen Washout), blood and sputum analysis, exercise testing (six-minute walk test). At Visit 1, participants will also complete computed tomography imaging at University Hospital, London Health Sciences Centre. Visits 2 and 4 have the option of being completed over the phone, in which case only questionnaires will be completed. Visit 5 is an optional 4-year follow-up.

This is a longitudinal study of the long-term impact of COVID-19 on the lungs. Participants will be followed over a period of up to 4 years and impacts of COVID-19 on the lungs will be measured with magnetic resonance imaging (MRI) using hyperpolarized xenon-129, pulmonary function tests, exercise capacity, computed tomography imaging and questionnaires.

This is a multi-center, randomized, double-blind, placebo-controlled study followed by an expansion cohort phase designed to investigate the safety, PK profile, and efficacy of a single injection of COVI-AMG in outpatient subjects with COVID-19 but are not likely to require hospital admission within 24 hours. Subjects will receive one of the following treatments: 40 mg COVI-AMG, 100 mg COVI-AMG, 200 mg COVI-AMG, or placebo. Subjects will be followed for 60 days after dosing.

This is a randomized, placebo-controlled study to assess the safety, PK profile, and efficacy of COVI-AMG in subjects with COVID-19.

The endonasal endoscopic approach (EEA) for pituitary surgery is standardly performed with the patient in supine position (SP). The semi-sitting position (SSP) is routinely used for the traditional microscopic transsphenoidal approach and also for posterior fossa surgery. The SSP results in lower intracranial pressure when compared to the supine position due to decreased venous congestion. As a result, intraoperative bleeding may be reduced, potentially leading to decreased surgical morbidity and improved surgical workflow. Studies during endoscopic sinus surgery have shown a significant reduction of blood loss when the patient is placed in a reverse Trendelenburg position with a head elevation of 30°. This study is to prospectively compare the standard supine (control group) and the semi-sitting position (head elevation of 30°; intervention group) in endoscopic endonasal pituitary surgery.

This study is to prospectively compare the standard supine (control group) and the semi-sitting position (head elevation of 30°; intervention group) in endoscopic endonasal pituitary surgery.

Purpose: To evaluate postoperative pain scores and postoperative opioid use in pediatric idiopathic scoliosis surgical patients using virtual reality (VR) as a method of immersive distraction compared with standard electronic use postoperatively.~Participants: Patients age 11-17 undergoing idiopathic scoliosis surgery on Enhanced Recovery After Surgery (ERAS) spine protocol at our institution.~Procedures (methods): Participants will be randomized to intervention arm (VR) or control arm (iPad). Baseline pain and anxiety scores will be assessed. On postoperative day 1, each patient will receive a visit by the research assistant who will assess pain scores, PCA use, etc. The intervention group will be offered a VR device for up to 30 minutes. The control group will be offered an iPad for up to 30 minutes. This visit will be performed twice on postoperative day 1. Follow up survey will be conducted at 48-72 hours and 7-10 days postoperatively.

The purpose of this study is to evaluate the use of virtual reality after scoliosis surgery in pediatric patients.

Achieving local anesthesia in children is one of the critical aspects of pain management and they effect the quality of treatment as well as behavior of child.~A contemporary engaging form of distraction is represented by virtual reality devices. Virtual reality (VR) devices create a virtual environment of view and sound that allow patients to be immersed in an interactive, simulated world to distract them from pain. The VR devices have a wide viewing field and three-dimensional displays that project the images right in front of the user. They not only show potentially attractive audio-visual stimuli, but also exclude all other visual environmental stimuli that may affect the patient.~While sweet-tasting reduce signs of pain during painful procedures. This effect is considered to be mediated both by the release of endorphins and by a pre absorptive mechanism related to the sweet taste.~The aim of this study is to determine the efficacy of sweet-testing compare to a virtual reality (VR) device in reducing injection pain and anxiety associated with local anesthesia in pediatric dental patients.~The device used in this study is Harga Miniso Vr Glass 3d terbaru, compatible with a mobile phone.~The sweet used is xylitol tablet The clinical trial is a randomized split-mouth assignment. Included patients are healthy positive children 5-12 years old requiring local anesthetic infiltration for conservative treatment of two primary maxillary molars bilaterally.~Eligible patients undergo two single-visit treatments after measurement of dental fear prior to each according to the Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS). Local anesthetic is delivered through buccal infiltration with conventional syringe, where is the sweet-test applied with first local anesthesia procedure and the virtual reality distraction is allocated to second local anesthesia procedure. Primary outcome measure will be pain felt during injection, reported by patient on visual analogue scale. Secondary outcome measures: self-reported anxiety during injection on Facial Image Scale; pain-related behavior according to Faces, Legs, Activity, Cry, Consolability (FLACC) scale; heart-rate dynamics; patient preference to local anesthesia method - sweet test infiltration or virtual reality device-assisted injection.

The aim of this study is to determine the efficacy of sweet in compare to virtual reality (VR) device in reducing injection pain and anxiety associated with local anesthesia in pediatric dental patients.~The clinical trial is a randomized split-mouth assignment. Included patients are 5 - 12 years old requiring local anesthetic infiltration with conventional syringe (CS) for conservative treatment of two primary maxillary molars bilaterally.~Eligible patients undergo two single-visit treatments after CFSS-DS measurement before each, whereas sweet is allocated to first local anesthesia procedure and VR is allocated to second local anesthesia procedure. Primary outcome measure will be pain felt during injection, reported by patient on visual analogue scale (VAS). Secondary outcome measures: self-reported anxiety during injection on FIS; pain-related behavior according to FLACC scale; heart-rate dynamics; patient preference to local anesthesia method - CS+sweet or CS+VR.

The purpose of this study was to explore the treatment of cognitive behavioral enhancement of insomnia (cbt-i plus), which was randomly divided into cbt-i plus intervention group (Study Group) and cbt-i intervention group (control group). The study group used the unified cognitive behavioral therapy manual for insomnia (cbt-i plus) for one-to-one individual treatment intervention, once a week, 45-50 minutes each time, a total of 8 times; the control group used the unified cognitive behavioral therapy manual for insomnia (cbt-i) for one-on-one treatment intervention, once a week, 45-50 minutes each time, a total of 8 times. The related indexes were evaluated at baseline, 2 weeks, 4 weeks and 8 weeks after enrollment, and were followed up at 12 weeks and 24 weeks after enrollment. Hypothesis: cbt-i plus is superior to cbt-i in efficacy and feasibility.

Objective to explore whether cbt-i plus is more effective and feasible for patients with insomnia complicated with anxiety and depression than the traditional cognitive behavioral therapy for insomnia.~Hypothesis: cbt-i plus is superior to cbt-i in efficacy and feasibility.

Chronic postsurgical pain (CPP) following lung cancer surgery is common with an observed prevalence of 20-60 %. Causes and health impact have been comprehensively studied. Current treatment consists of combination of pain medication, physiotherapy and psychological therapy.~Botulinum Toxin A (BTX-A) has shown promising effects in a variety of chronic postsurgical pain syndromes. The use of BTX-A in lung cancer patients has only been presented in few case reports. No randomized clinical controlled trials (RCT) has been executed to date.~Study objectives:~Primary:~Determine recruitment potential among cured lung cancer patients with CPP for an RCT and if the method of BTX-A administration is feasible and acceptable to the test subjects.~Secondary:~Early stage testing of the hypothesis that CPP following thoracic surgery can be treated with this novel method.~Methods:~Recruitment of test subjects:~Test subjects are recruited among former lung cancer patients with chronic postsurgical pain, who have undergone radical treatment for lung cancer at the Department of Cardiothoracic Surgery, Aalborg University Hospital. Potential test subjects are invited by mail / e-mail.~Randomization and blinding:~Test subjects are randomized to receive a series of injections with either Onabotulinum Toxin A (active agent) or inactive normal saline (Placebo). Neither test subject nor investigator will know which treatment is given until the end of the trial.~Experimental treatment:~The investigator examines the skin area of the test subject at the operation site and performs a sensory examination with pin prick and sensory brush. The area is located and marked and divided into quadrants of one square centimeter. An area of maximum 40 square centimeters is marked.~At a single treatment session, test subjects receives either active agent or placebo through a series of subcutaneous injections. One injection is given in each marked quadrant of the treatment area. The maximal number of injections is 40.~Follow-up:~After the treatment, test subjects report pain symptoms and intensity, use of pain medication and occurrence of adverse events weekly.~After 30 and 90 days after treatment more comprehensive and additional data is collected concerning neuropathic symptoms, activities of daily life, general health and level of function.~Data collection Data is collected by questionnaires delivered to test subjects by mail or digitally.~Endpoints:~Primary:~Recruitment of 30 test subjects.~Half of the first half of included test subject must complete the treatment.~Half of test subjects in total mus complete the treatment.~Secondary:~Pain at rest, coughing and when active Numerical rating score (NRS) for presence of pain before and after treatment and course of pain symptoms.~General Health Short form 36 Health Survey on physical, social and mental level of function on a score from 0 to 100.~Neuropathic Pain Symptoms Inventory (NPSI) NRS~Activities of daily life Impact and intensity of pain categorically in 16 situations of daily life.~Patient's Global Impression of Change (PGIC) Rating of global change perceived by the test subject from More Worse to Much better and a scale from 0 to 10.

Chronic postsurgical pain following lung cancer surgery is common with and 20-60 % develop chronic pain which persists more than six months after surgery. Causes and health impact of this pain have been comprehensively studied. Current treatment consists of combination of pain medication, physiotherapy and psychological therapy.~Botulinum Toxin A (BTX-A) has shown promising effects in a variety of chronic postsurgical pain syndromes. The use of BTX-A in lung cancer patients has only been presented in few case reports. No randomized controlled trials (RCT) have been executed to date.~Study objectives:~Determine recruitment potential among cured lung cancer patients with chronic postsurgical pain for an RCT and if the method of BTX-A administration is feasible and acceptable. Further more, this study will contribute to the stage testing of the hypothesis that chronic pain following thoracic surgery can be treated with BTX-A.~Methods:~Recruitment of test subjects:~Participiants are recruited among former lung cancer patients with chronic postsurgical pain, who have undergone radical treatment for lung cancer at the Department of Cardiothoracic Surgery, Aalborg University Hospital. Potential test subjects are invited by mail / e-mail.~Randomization and blinding:~Participants are randomized to receive a single series of subcutaneous injections with either Onabotulinum Toxin A (active agent) or inactive normal saline (Placebo) at the former operation site. Neither participant nor investigator will know which treatment is given until the end of the trial.~Data collection:~Data is collected by questionnaires delivered and answered by mail or digitally.~Data on the possible effects and possible adverse reactions are collected at multiple times until three months after treatment.

The primary objective of the study is to evaluate the clinical performance of test lens (Orion) in comparison with control lens (Gemini) over a period of two weeks of wear. This is a double-masked, randomized, bilateral, two-week crossover, dispensing study.

The primary objective of the study is to evaluate the clinical performance of test lens (Orion) in comparison with control lens (Gemini) over a period of two weeks of wear.

Qigong, a traditional Chinese mind-body exercise, has been shown to improve balance and gait in several neurological conditions; however, community-delivered qigong has never been assessed for people with multiple sclerosis (MS). We assessed the feasibility of community qigong classes for people with MS and explored outcomes of balance, gait, and quality of life (QOL).~Twenty adults with MS were randomly assigned to 10 weeks of community qigong classes or wait-list control. Feasibility criteria included recruitment, retention, adherence, and ability to participate in qigong movements. Secondary outcome measures included physical tests of mobility, gait and balance, and participant-reported mobility, depression, anxiety, fatigue, and QOL.~Because this is a small feasibility study, the data collected are meant to be hypothesis-generating. Any clinically meaningful trends toward improvement will justify further exploration of qigong for MS in a larger clinical trial.

This feasibility study explores a community-based qigong intervention for people with multiple sclerosis (MS). The primary aim is to assess the feasibility of weekly community qigong classes for people with MS. The secondary aim is to explore the effects of qigong on balance, gait, mood, fatigue, and quality of life.

PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.~The primary objective of Phase 1 monotherapy is to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of PC14586. Secondary objectives are to characterize the pharmacokinetic (PK) properties, safety and tolerability, and to assess preliminary efficacy including overall response rate (ORR).~The primary objective of Phase 1b Combination Therapy Treatment Arm is to establish the MTD/RP2D of PC14586 when administered in combination with pembrolizumab. Secondary objectives of Phase 1b Combination Therapy Treatment Arm are to characterize PK, safety and tolerability, and to assess preliminary efficacy of PC14586 when administered in combination with pembrolizumab, including ORR.~The primary objective of Phase 2 monotherapy is to assess the ORR as determined by blinded independent central review. Secondary objectives of include the safety, PK properties, quality of life, and other efficacy measures of PC14586 at the RP2D.

This study will assess the safety, tolerability, and efficacy of multiple dose levels of PC14586 alone and in combination with pembrolizumab in participants with advanced solid tumors containing a TP53 Y220C mutation.

The objective of this study is to assess the safety and performance of the Shockwave M5+ Peripheral IVL System to treat calcified peripheral arteries in pre-market countries, and to assess continued safety and effectiveness in the US. A minimum of 40 lesions in up to 40 subjects at up to 10 sites in Australia, New Zealand and the US will be enrolled with the aim of treating at least 20 target lesions with the 8.0 mm IVL catheter. A maximum of three target lesions may be treated per subject. Subjects with moderate and severely calcified iliac and femoropopliteal artery disease presenting with Rutherford Category 2 to 5. Approximately 6 months of enrollment at up to 10 sites in Australia, New Zealand and the US. Study subjects will be followed through discharge, 30 days, 6 and 12 months. Duplex Ultrasound (DUS) assessments will be completed at 12 months. Total anticipated study duration is 18 months. The primary safety endpoint is Major Adverse Events (MAE) at 30 days defined as: need for emergency surgical revascularization of target limb; unplanned target limb major amputation (above the ankle); symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization ; or perforations that require an intervention, including bail-out stenting. The primary performance endpoint is technical success defined as final residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion by angiographic core lab.

Prospective, multi-center, single-arm study of the M5+ Peripheral IVL system to treat calcified peripheral arteries.

This study aims to determine the safety and efficacy of first-line, risk-stratified rituximab-based MCD treatment in Malawi in a single-arm, phase II clinical trial. The investigators will enroll 27 subjects with newly diagnosed or previously treated MCD (who have not previously received rituximab) requiring treatment (B symptoms or hemoglobin <10 g/dL). Subjects will be treated with four weekly doses of rituximab. High-risk subjects (defined as patients with Eastern Cooperative Oncology Group (ECOG) performance status >2 or hemoglobin <8 g/dL) will also receive etoposide chemotherapy. Subjects will be followed for one year for toxicity and two years for survival. The primary outcome will be safety, defined as the frequency of ≥Grade 3 treatment-related Common Terminology Criteria for Adverse Events (AEs). Secondary outcomes will be event-free survival (death, progression, or development of NHL) and 1- and 2-year overall survival (OS). The investigators also aim to compare the cost-effectiveness of first-line rituximab treatment for MCD in Malawi to chemotherapy (using the investigators' historical controls).

The purpose of this study is to determine the safety and efficacy of first-line, risk-stratified Rituximab-based Multicentric Castleman Disease (MCD) treatment in Malawi in a single-arm, phase II clinical trial. This study also aims to compare the cost-effectiveness of first-line Rituximab treatment for MCD in Malawi to chemotherapy.

Women frequently experience lower-back or pelvic pain during pregnancy. This may lead to a need for physical therapies such as physiotherapy, osteopathy or massage in late pregnancy. Several case-control studies, and a recent individual patient data meta-analysis has demonstrated an association between going to sleep position and late stillbirth (a greater than 2-fold increased risk with going to sleep supine) and increased frequency of daytime naps. This is thought to be related to maternal haemodynamic changes when a mother lies supine in late pregnancy which decreases cardiac output and uterine blood flow. These changes are accompanied by alterations in fetal behaviour which are consistent with a reduction in oxygenation. This observation raises concerns that spending extended periods laid flat could be detrimental to baby's health. However, it is not known whether lying flat for extended periods for physical therapies could also alter a baby's heart rate or levels of oxygen. One small study of 33 women from Brazil which randomised the order of maternal positions found that there were no differences in a mother's heart rate, blood pressure, oxygen saturation or baby's heart rate between a supine, lateral and prone position (bent over a concave couch). However, there were observed changes in mother's breathing rate and systolic blood pressure when a mother laid on her front. Nevertheless, all the women reported feeling comfortable lying flat (on a bent surface). However, in this study women only spent 6 minutes in each position which is less than a woman would be expected to spend lying in a position for a session of physical therapy. Therefore, further work is required to determine whether spending extended periods laid prone is safe for mother and baby.~The co-investigator (Karli Büchling) has developed a cushion to support mothers in a prone position (Anna cushion). This study will investigate whether adopting this position supported by the cushion is associated with changes in mother's heart rate, blood pressure, breathing rate and blood oxygen levels and fetal heart rate as assessed by the cardiotocograph. The investigators will also ask about mother's levels of comfort while she is laid flat. The findings of this study will give an indication whether supporting a mother to lie in a prone position for physical therapies is safe and comfortable.

During pregnancy women may need or choose to undergo physical therapies such as physiotherapy, massage or osteopathy. Recent findings from studies of mothers who had a stillbirth in late pregnancy found that the position in which women went to sleep in was linked to stillbirth, as was the frequency of day time naps. This link is thought to be due to changes in mother's blood flow from her heart when lying flat leading to changes in the amount of oxygen going to her baby. This raise concerns that spending extended periods laid flat could be detrimental to baby's health. However, it is not known whether lying flat for extended periods for physical therapies could also alter a baby's heart rate or levels of oxygen. One small study of 33 women from Brazil found that there were no differences in a mother's heart rate, blood pressure, oxygen saturation or baby's heart rate. But there were changes in mother's breathing rate and systolic blood pressure when a mother laid on her front. All the women reported feeling comfortable lying flat (on a bent surface). However, in this study women only spent 6 minutes in each position which is less than a woman would be expected to spend lying in a position for a session of physical therapy. The investigators plan a study to assess whether using a device to support a prone position (Anna cushion) would be associated with changes in mother's heart rate, blood pressure, breathing rate and blood oxygen levels and baby's heart rate. The investigators will also ask about mother's levels of comfort while she is laid in the prone position. The findings of this study will give an indication whether supporting a mother to lie in a prone position for physical therapies is safe and comfortable.

DNA damage repair (DDR) pathways can modulate cancer risk, progression and therapeutic responses. Germline mutations in genes encoding key players in the DNA-damage response (DDR), including BRCA1, BRCA2,BLM, FANCA, TP53, RAD51C, and MSH2, result in cancer susceptibility syndromes, in part because failure to adequately protect the genome against endogenous and exogenous sources of DNA damage results in the accumulation of oncogenic mutations. The mechanistic rationale for the combination of PI3K and PARP inhibitors is that PI3K inhibition leads to a downregulation of BRCA1/2 proteins, which increase the degree of HRR deficiency CYH33 is a novel, highly potent and selective inhibitor of phosphatidylinositol 3-kinase αsignificantly inhibited the activities of wild-type and mutant PI3Kα kinase as well as the specific mutant of E542K, 1047R or E545K, On July13, 2018, a Phase I first-in-human dose escalation and expansion single-agent study of CYH33 (CYH33-101) started in China (ClinicalTrials.gov identifier: NCT03544905) identify the MTD of CYH33 single agent was 40 mg. The most common treatment related adverse events (>5%) of Grade 3 was hyperglycemia. No treatment-related Grade 4 adverse event or death was reported in the ongoing trial by the cut-off date. In this combination study will assess if this combination will optimize anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2 dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.

The purpose of this study is to assess the safety, tolerability and preliminary efficacy of CYH33 in combination with olaprib in patients with DDR gene mutations and/or PIK3CA mutations, in patients who have progressed on prior PARP inhibitor, and in patients with recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer who are platinum resistant or refractory. The study will assess if this combination will optimize anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2 dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.

Throughout the UK, paediatric transport services are responsible for the stabilisation and transport of critically unwell children. This involves moving children from district general hospitals to receive specialist care in tertiary centres and moving children between tertiary and quaternary centres in order to provide the appropriate level of specialist care.~Critically unwell children often require infusions of essential, life-saving medications during episodes of transport. Disruption of these infusions can be destabilising and even life-threatening. Examples of essential infusions include the use of prostin in duct-dependent congenital heart disease, vasoactive/inotropic medications in shock and sedation and muscle relaxants to ensure comfortable, safe transfer.~Critically unwell patients often require support in the form of inotropes/vasopressors to support cardiac contractility and alter vascular tone and are commonly used in the treatment of shock. Physiological response to vasoactive/inotropic drugs is rapid and measurable in terms of cardiovascular status through observing changes in heart rate, blood pressure and oxygenation of peripheral tissues (pulse oximetry). As such these medications offer the potential to observe whether syringe driver delivery variations as mediated through the effect of g-forces exert measurable physiological instability in transported patients.~G-Forces Pilot is a prospective, observational, case-control, feasibility study investigating the effect of G-forces as measured by an accelerometer against physiological parameters of heart rate, invasive blood pressure measurement and oxygen saturations in vivo during episodes of transport. The study aims to understand the relationship between the physics of transport on physiological parameters and to assess whether syringe driver delivery (previously demonstrated to be affected by G-forces in-vitro), is responsible for physiological variations in transported patients requiring vasoactive/inotropic infusions.~The investigators propose to examine this relationship by obtaining and analysing data on physiological parameters in patients during episodes of transport to assess:~(i) Whether G-forces experienced by being in a moving ambulance affect the stability of patient physiological parameters.~(ii) How variations in syringe driver delivery mediated through the effects of G-Forces affect patients in transit as evidenced through instability in physiological parameters whilst receiving vasoactive/inotropic infusions.~This will be examined by the comparison of a control and study group. The control group will consist of patients with full monitoring (including an arterial line), without vasoactive/inotropic support. The study group will consist of patients with full monitoring (including an arterial line) receiving vasoactive/inotropic support through a syringe driver. Data analysis will assess the strength of correlation between patient observations and experienced g-forces recorded during the episode of transport to answer the study question.

G-Forces On Retrieved ChildrEn (Pilot) Study is a feasibility study looking at the effect of G-Forces in vivo during episodes of paediatric critical care transport. The study aims to (i) understand the relationship between the physics of transport on physiological parameters and (ii) assess whether syringe driver delivery (previously demonstrated to be affected by G-forces in vitro), is responsible for physiological variations in transported paediatric patients requiring vasoactive/inotropic infusions.

The study is a Phase II, single-arm, open-label, single-dose clinical trial, and its primary objective is to evaluate the efficacy and safety of CNCT19 Cell Injection in the treatment of relapsed or refractory NHL. The study consists of screening period (8 weeks), treatment period (4 weeks), and follow-up period (2 years at most).

The study is a Phase II, single-arm, open-label, single-dose clinical trial, and its primary objective is to evaluate the efficacy and safety of CNCT19 Cell Injection in the treatment of relapsed or refractory NHL.

Prostate cancer is one of the leading cause of cancer death among males worldwide. The objective of this phase II, randomized, controlled, open label study is to evaluate the effectiveness and safety of MAO-B (Monoamine oxidases-B) inhibitor selegiline plus docetaxel therapy. Patients diagnosed with metastatic, castrate-resistant prostate adenocarcinoma are randomly divided into two groups. One group (control arm) receives docetaxel (75 mg/m2 IV every 3 weeks for maximum of 12 cycles). Another group (experimental arm) receives docetaxel (75 mg/m2 IV every 3 weeks for maximum of 12 cycles) plus selegiline (daily 10 mg tablet). Patients are followed up for 36 months or until the end of the trial, death or withdraw from this study due to other reasons. The primary endpoint of this study is the proportion of patients without progression at month 9. The secondary endpoint is proportion of patients without progression at month 12/18, progression-free survival, overall survival, duration of PSA response, radiological response rate, PSA response rate, health-related quality of life and safety.

The objective of this clinical study is to evaluate the effectiveness and safety of selegiline plus docetaxel therapy compared to the standard of care - docetaxel therapy - among patients diagnosed with metastatic, castrate-resistant prostate adenocarcinoma.

Repetitive Transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression that involves brief magnetic stimulation pulses on the dorsolateral prefrontal cortex (DLPFC) brain region. The ultimate goal of this treatment is to increase excitability and long-term plasticity in DLPFC, a brain region shown to be hypo-active in depression. Unfortunately, rTMS only has low to moderate efficacy; remission rates for patients range from ~15-30% in large randomized controlled trials. The focus of this research is to develop a next-generation rTMS protocol that is guided by the basic principles underlying brain plasticity, in order to improve the efficacy of rTMS for the treatment of depression. Specifically, in this study the investigators will test rTMS paired with a depression-relevant cognitive state of internal attention. Meditative internal focus has been shown to benefit depression. Our own research shows that the neural correlates of attention-to-breath are associated with greater mindfulness. Hence, in this study we will pair breath training with rTMS neuro-stimulation.

Repetitive Transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression that involves brief magnetic stimulation pulses on the dorsolateral prefrontal cortex (DLPFC) brain region. The ultimate goal of this treatment is to increase excitability and long-term plasticity in DLPFC, a brain region shown to be hypo-active in depression. Unfortunately, rTMS only has low to moderate efficacy; remission rates for patients range from ~15-30% in large randomized controlled trials. The focus of this research is to develop a next-generation rTMS protocol that is guided by the basic principles underlying brain plasticity, in order to improve the efficacy of rTMS for the treatment of depression. Specifically, in this study the investigators will test rTMS paired with a depression-relevant cognitive state of internal attention.

Current research has shown evidence that phytocannabinoids may have a promising therapeutic potential in a variety of physical and psychological ailments, and cannabidiol (CBD) is of particular interest due to its positive safety profile, non-intoxicating effects and widespread capabilities in a number of musculoskeletal diseases. Three primary reasons people consume CBD on a global basis, in addition to the fact that it is non-intoxicating, are for symptomatic (pain) relief, anxiety reduction, and improved sleep quality. Very little is known about CBD and how it functions in the body from both an efficacy and mechanistic perspective, especially in humans. There is a large consumer base for this product that will be expanding exponentially in the next few years. Most of the evidence available is anecdotal from the personal testimony of consumers. We aim to determine the efficacy of a controlled short-term trial of CBD ingestion for reducing symptomatic response and facilitating recovery following induced muscle injury. In addition, we aim to identify if the effects are dose-dependent by utilizing a low-dose (25 mg/day), high-dose (62.5 mg/day) and vehicle-control (0 mg/day) ingestion regimen. We will assess, in serial fashion, symptomatic response, functional limitations and recovery of the quadriceps muscle following induced injury in which selected doses of CBD oil will be administered orally during a 15-day pre-injury consumption and post-injury recovery phase. A double-blind, randomized, three-arm study design will be used and participants will be randomly assigned to either a high dose (n=15), low dose (n=15), or vehicle control group (n=15). Our clinical outcomes include measures of muscular pain and disability along with measures of pain-related fear and anxiety. Our laboratory-based study design is desirable and advantageous because it is a controlled method of tracking individuals using an experimental model of injury that is translatable to clinical populations. Another advantage of this study design is that it will address, in parallel fashion, two of the primary reasons people are consuming CBD - symptomatic relief and anxiety reduction. This exploratory study will provide preliminary data needed to support the hypotheses of a planned larger scale application.

The study aims to determine the efficacy of a controlled short-term trial of CBD ingestion for reducing symptomatic response and facilitating recovery following induced muscle injury. A double-blind, randomized, three-arm study design will be used and participants will be randomly assigned to either a high dose (n=15), low dose (n=15), or vehicle control group (n=15). The clinical outcomes include measures of muscular pain and disability along with measures of pain-related fear and anxiety.

Peripheral artery disease (PAD) is characterised by atherosclerotic lesions of the arteries in the lower limbs, resulting in a reduction of blow flow (Hiatt, 2001). Globally, it is estimated that 236 million people are living with PAD, with the number of cases increasing by 24% from 2000 to 2010. A classic symptom of PAD is intermittent claudication (IC), characterised by ischemic muscle pain precipitated by exertion and relieved by rest. IC is associated with various comorbidities such as diabetes mellitus, hypertension and dyslipidaemia as well as reductions in physical function, quality of life, and balance. National and international guidelines recommend supervised exercise therapy as first line treatment for patients with IC.~To assess IC impairment in response to an exercise intervention, maximal walking capacity is typically the primary outcome in randomised controlled trials (RCT's). This involves a patient walking for as long as possible until ischemic leg symptoms, fatigue or other symptoms prevent them from continuing. This is assessed by a number of exercise testing protocols including the six-minute walk test (6MWT). The American Thoracic Society provide guidelines for performing a standardised 6MWT including verbal phrases that are conducted every minute. Conversely, Montgomery and Gardner suggest encouragement every two minutes. Encouragement has been shown to significantly affect walking performance by as much as 30 meters in heart failure and respiratory disease populations. However the effect of encouragement on walking performance in people with IC is yet to be investigated.

Peripheral artery disease (PAD) is characterised by a build up of fatty plaque in the arteries in the lower limbs, resulting in a reduction of blow flow to the muscles. Globally, it is estimated that 236 million people are living with PAD. A classic symptom of PAD is intermittent claudication (IC) which is characterised by muscle cramps in the lower limbs, typically brought on by exercise and relieved at rest. Exercise is recommended at first line treatment for IC. However to assess IC symptoms in response to an exercise study, maximal walking capacity (the furthest they can walk before it becomes too painful to walk) is typically the main measure. A patients walking capacity is assessed by a number of exercise testing protocols including the six-minute walk test (6MWT), where patients walk for six minutes with the aim to walk as far as they can in the time allotted. Patient encouragement has been shown to improve walking performance by as much as 30 meters in heart failure and respiratory disease populations. However the effect of encouragement on walking performance in people with IC is yet to be studied.

The aim of this study is to evaluate and compare the hypotensive efficacy at 24 months between two implants in glaucoma surgery. Non-perforating deep sclerectomy surgery with non-resorbable uveoscleral implant associated with absorbable collagen matrix versus non-perforating deep sclerectomy surgery with isolated absorbable collagen matrix implant.

The aim of the study is to evaluate and compare the hypotensive efficacy at 24 months between non-perforating deep sclerectomy surgery with non-resorbable uveoscleral implant associated with absorbable collagen matrix versus non-perforating deep sclerectomy surgery with isolated absorbable collagen matrix implant.

Breast cancer is the commonest type of malignancy in women. Chronic postoperative neuropathic pain may appear either in the early postoperative period or at a later stage, usually 3-6 months post-operatively. Chronic post-operative pain syndrome of any magnitude usually involves 19-57% of patients that have undergone any kind of surgical procedure, while 5% of them experience intense symptoms. Risk factors for developing post-mastectomy pain syndrome include younger age, increased Body mass Index (BMI), psychological profile, co-existence of other painful conditions, pre-operative radiotherapy/chemotherapy, type of surgical procedure and anaesthesia, persistent acute postoperative pain, etc. Consequently, chronic post mastectomy pain syndrome results in significant psychosomatic sequelae with variable social impacts for the female patients.~The aim of the present study will be to investigate the incidence of chronic pain following breast cancer surgery in Cyprus, discover its associated risk factors and explore the impact of Pecs Blocks on the appearance of post mastectomy chronic pain symptoms.~During the preoperative visit, the women will be informed about the study and will be instructed to the use of the pain numeric rating scale (NRS) graded from 0 to 10. Standardized anesthesia will be administered. All patients will receive 1000 mg of paracetamol and 0.07 mg/ Kg of morphine intraoperatively. In the Post-Anesthesia Care Unit (PACU), patients will receive additional morphine boluses on request, until NRS score is lesser or equal than 4. Postoperative nausea and vomiting will be treated with ondansetron 4 mg iv. After discharge from PACU, patients will receive a combination of paracetamol 1 gr/6h and im pethidine 75 mg on request, as per hospital protocol.~Numerical rating scores (NRS) at rest and movement will be measured at 6h, 12h and 24h postoperatively. Additionally, the time to first request for analgesia after surgery will be noted.~All patients will also be evaluated 3 and 6 months after surgery with the use of NRS at rest and movement and additionally, via the use of Douleur Neuropathique (DN4) questionnaire for the occurence of neuropathic pain.

The aim of the present study is to investigate the incidence of chronic pain following breast cancer surgery in Cyprus, discover its associated risk factors and explore the impact of Pecs Blocks on the appearance of post mastectomy chronic pain symptoms

This study will use a non-invasive form of spinal stimulation, called transvertebral direct current stimulation, or tvDCS. It currently is not clear what effects this type of stimulation has on the excitability of the brain and spinal cord in people with spinal cord injury. In this study, subjects will participate in 3 sessions, with at least 1 week in between sessions, during which they will get a different condition of tvDCS. We will test the excitability of the brain and spinal cord before and after tvDCS in each session.

This study will evaluate the effects of non-invasive stimulation of the spinal cord in people with spinal cord injury.

Transnasal fiberoptic laryngoscopy (TFL) is gold standard for visualising the larynx. TFL has been used to visualize the laryngeal response patterns during non-invasive therapeutic interventions, as during Mechanically Assisted Cough in patients with Amyotrophic Lateral Sclerosis. The examinations revealed that the larynx adducted during the application of positive pressures, which restricted the airflow and reduced the efficacy of the treatment. The higher treatment pressures resulted in ineffective interventions as a result of the adducted vocal cords obstructing flow. This knowledge has changed the treatment approach for patients with possible upper airway instability by individualizing the treatment pressures and flow due to laryngeal responses.~TFL may cause slight discomfort when placing the laryngoscope. Diagnostic ultrasound is non-invasive easily applicable technique that has gained increasing popularity in diagnosing cardiopulmonary and laryngeal conditions during the recent times. The aim of the study is to investigate whether the diagnostic ultrasound of the larynx can be as accurate as TFL during Mechanically Assisted Cough and Non-Invasive Ventilation (NIV). The present study will include healthy participants. Hypothesis is that diagnostic ultrasound of larynx can provide clinical valuable information of the laryngeal response patterns during Mechanically Assisted Cough and NIV.~The aims of the study are:~To evaluate the feasibility of diagnostic ultrasound imaging of the larynx, and to compare to the gold standard of TFL used during ongoing NIV and Mechanically Assisted Cough in healthy subjects.~To evaluate the feasibility of ultrasound imaging if the diaphragm during ongoing NIV and Mechanically Assisted Cough in healthy subjects.

The study examines if diagnostic ultrasound imaging of larynx and diaphragm can be as accurate as transnasal fiberoptic laryngoscopy in visualizing the larynx during NIV and Mechanically Assisted Cough interventions.

In most cases, patients who have early stage endometrial cancer undergo a surgery to remove the uterus, cervix, tubes, ovaries, and occasionally lymph nodes. This is usually done through a minimally invasive (not a large incision) surgery. To accomplish this, the uterus needs to be manipulated (moved around) to help the surgeon complete your surgery. This is usually done with a device called a uterine manipulator and the majority of surgeons use this device in any patient undergoing a minimally invasive hysterectomy (removal of the uterus and cervix).~Even though the majority of surgeons use a manipulator, there are some surgeons who believe there is a possibility that cancer cells inside the uterus can be spilled into the abdomen through the fallopian tubes. This may cause a higher risk of spreading the cancer and or of the cancer coming back.~Currently, there are very limited research studies directly looking at whether the uterine manipulator may cause these cells to appear in the abdomen.~The purpose of this study is to see if patients undergoing a minimally invasive surgery for early stage uterine cancer have cancer cells in the fluid that is obtained at the time of their surgery when a uterine manipulator is placed versus patients who do not have a uterine manipulator placed.~A computer program will randomly assign the subjects to one of two groups. One group will have minimally invasive surgery with the use of a uterine manipulator and the other group will have minimally invasive surgery without the use of a uterine manipulator.~Researchers will use the information from this study to decide how best to take care of patients undergoing minimally invasive surgery for uterine cancer.

This is a prospective, multi-center, randomized non-inferiority phase III study to evaluate if patients undergoing a minimally invasive surgery for early stage uterine cancer have cancer cells in the fluid that is obtained at the time of their surgery when a uterine manipulator is placed versus patients who do not have a uterine manipulator placed.

This study is a Phase 1 randomized, double-blind, placebo-controlled, single- and multiple-dose study evaluating safety, tolerability, and pharmacokinetics, with an open-label initial food effect and CYP3A drug-drug interaction study, of FTX-6058 in healthy adult subjects and a randomized, double-blind, placebo-controlled, multiple-dose study in adult subjects with sickle cell disease (SCD).~This study will comprise 5 parts and will be conducted in healthy adult subjects and adult subjects with sickle cell disease (SCD) (Part E only).~Part A will be a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study in up to 8 cohorts of healthy adult subjects. Part B will be a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study in up to 6 cohorts of healthy adult subjects dosed once daily for 14 days. Part C will be an open-label pilot food effect study in healthy adult subjects randomized to take FTX-6058 with and without a high-fat meal, and Part D will be an open-label study to evaluate the potential of FTX-6058 to induce CYP3A (using midazolam) in healthy adult subjects. Part E will be a randomized, double-blind, placebo-controlled, multiple dose study in adult subjects with sickle cell disease (SCD). Subjects in Part E may enroll into Study 6058-SCD-101 (NCT 05169580) Part A (6 mg cohort) at the Day 15 visit; subjects that enroll into 6058-SCD-101 will not need to undergo the Safety Follow-up visit.~The primary endpoint of the study is to evaluate the safety and tolerability of FTX-6058 in healthy adult subjects and adult subjects with sickle cell disease as measured by the frequency of adverse events. Secondary endpoints include evaluation of the pharmacokinetics of single dose and multiple dose FTX-6058 in healthy adult subjects, pharmacokinetics of multiple dose FTX-6058 in adult subjects with sickle cell disease, evaluation of the potential effect of food on FTX-6058 and evaluation of the potential for CYP3A induction by FTX-6058 in healthy adult subjects.

This is a study to evaluate the safety, tolerability and pharmacokinetics of FTX-6058 in healthy adult subjects and adult subjects with sickle cell disease (SCD).

A Phase 1 Clinical Trial to evaluate the tolerability and pharmacokinetics in healthy adult volunteers after administration of CKD-348 and co-administration of CKD-828, D097, D337.

A Clinical Trial to evaluate the Pharmacokinetics and Tolerability of CKD-348

Over the last 15 years, robot-assisted laparoscopic radical prostatectomy surgery has seen a considerable rise in France. To date, it represents the most common surgical technique for radical prostatectomies, compared with standard procedure such as open retropubic radical prostatectomy or laparoscopic radical prostatectomy (8000 procedures/year, 40% of surgeries). In 2016, the French Health Authority (HAS) published a report on the robot-assisted laparoscopic radical prostatectomy practice that highlighted the small amount of available convincing data to provide evidence for a significant clinical benefit. There were no published data on overall or progression-free survival compared with other surgical procedures, with an important organizational and financial impact for healthcare institutions and patients. The question of the clinical benefit and the cost-effectiveness ratio of this surgical procedure is still relevant taking into account that randomized studies are difficult to carry out and that results of prospective registers will be available in many years. In this context, the use of the French National Claims Database (SNDS) appears to be the best short-term and reduced-cost solution to identify patients who benefited from the three surgical procedures since the rise of robotics. It would provide real-life data to national institutions in order to conclude on the opportunity to set a specific hospital tariff for the robot-assisted laparoscopic radical prostatectomy. This study aims to assess the cost-effectiveness ratio and the clinical benefit (survival, disease recurrence, functional results) of the robot-assisted laparoscopic radical prostatectomy compared with other procedures using real-life data from SNDS. The population of patients who benefited from robot-assisted surgery will be identified in the SNDS through a practices survey, allowing the identification of centres fully converted to robotics.

This study aims to assess the cost-effectiveness ratio and the clinical benefit (survival, disease recurrence, functional results) of the robot-assisted laparoscopic radical prostatectomy compared with other procedures using real-life data from SNDS. The population of patients who benefited from robot-assisted surgery will be identified in the SNDS through a practices survey, allowing the identification of centres fully converted to robotics.

Spinal muscular atrophy (SMA) is a severe, debilitating disease and is an important source of morbidity and mortality of children. Novel disease modifying therapies can alter the natural course of the disease. However, many aspects of their action remain unknown. Metabolomics is the large-scale study of metabolites, within cells, biofluids, tissues or organisms. Collectively, these small molecules and their interactions within a biological system are known as the metabolome.~The aim of this study is to evaluate whether the metabolome of patients with SMA before the initiation of disease modifying therapy with nusinersen differs from the metabolome of healthy individuals. Next, we would like to asses whether tretament with nusinersen alters the metabolome of patients with SMA. Utilizing metabolomics, we would like to assess whether we can identify parameters reflecting the state of the disease in a particular patient, and parameters with diagnostic and/or prognostic value. Using metabolomics, we will aim to identify SMA patients that will positively respond to gene therapy.

The aim of the proposed project is to evaluate whether the metabolome of patients with spinal muscular atrophy (SMA) before the initiation of treatment with nusinersen differs from the metabolome of healthy individuals and whether it changes 14 months after treatment with nusinersen.

Patients meeting the inclusion and exclusion criteria and volunteer to participate will be randomly assigned to Active CES Therapy and Sham CES Therapy groups. Before start of the treatment (active or sham), their medication details or any other form of treatment they are on will be noted down. These patients will be assessed on self-rated Beck Depression Inventory and clinician rated Hamilton Depression Rating Scale. They will be also assessed on neuropsychological functions of attention, executive functions, memory, information processing and emotional processing evaluation using Emotional Test Battery. In addition, 25 patients from each group will undergo EEG recording whilst they perform computer based tasks. These assessments will take place at 4 time points (Pre-treatment, 1 month after treatment, at 3 months, and at 6 months after treatment).~The study will use scalp based electroencephalogram (EEG) to record the brain activity of participants whilst they perform computer based tasks. The aim is to understand if there would be changes in the neural signals following cranial electrotherapy stimulation. Investigators propose to use EEG to investigate if CES therapy will modulate brain responses in a way that leads to better information processing as a mechanism to improve depression. Furthermore, researchers will also investigate changes in EEG based brain connectivity patterns following CES therapy. Therefore, as a mechanism of action for CES therapy could be changes in the functional brain connectivity for efficient information processing. EEG investigation will be helpful to understand this connectivity based mechanism following CES.

This study will examine the effect of cranial electrotherapy stimulation (CES) treatment on adults with depression. Scalp based electroencephalogram (EEG) will be utilized to record the brain activity of participants whilst they perform computer based tasks. The aim is to understand if there would be changes in the neural signals following CES.

This is a Phase 1, multi-center study with parallel groups. The study employs a single-dose, open-label design in subjects with mild, moderate, or severe hepatic impairment along with matched healthy control subjects with normal hepatic function. Subjects with normal hepatic function will be matched with subjects with hepatic impairment for gender, age (± 10 years), body weight (± 15%), and smoking status (smoker or non-smoker).~Up to a total of 48 participants will be enrolled in this study (approximately 8 in each mild [Child-Pugh A], moderate [Child-Pugh B], severe hepatic impairment [Child-Pugh C] groups), and up to 24 healthy control subjects). Each participant will receive a single oral dose of 300 mg of icenticaftor (QBW251) on Day 1 under fasting conditions.~The study is comprised of an up to 28-day screening period (Days -28 to -1), a baseline evaluation (Day -1) prior to treatment on Day 1, and a follow-up period of 7 days for pharmacokinetics (PK) sample collection (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose). A safety follow-up contact will be done 30 days after administration of the study drug.~The primary purpose of this study is to evaluate the effect of hepatic impairment on the systemic PK, safety, and tolerability of icenticaftor in participants with varying degrees of hepatic impairment.

The primary purpose of this study is to evaluate the effect of hepatic impairment on the systemic pharmacokinetics, safety, and tolerability of icenticaftor in participants with varying degrees of hepatic impairment.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical situation with multiple underlying causes. The diagnosis of HFpEF is challenging which requires clinical signs/symptoms of HF, a normal or mildly impaired systolic function measured by left ventricular ejection fraction (LVEF), and evidence of diastolic dysfunction. There are no significant improvements in treatment of HFpEF in recent years and the results in the major clinical trials for HFpEF were disappointed. One major reason is the heterogeneity of HFpEF, which contains several diseases under the same entity.~Small deposits of amyloid are found in the elder hearts in up to 25% of the autopsies. These deposits are mainly composed by wild-type transthyretin (TTR). Transthyretin amyloidosis cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin protein. It is classified into 2 groups by the genetics of Transthyretin amyloidosis (ATTR): wild-type (ATTRwt) or hereditary (hATTR or ATTRm). ATTR CA, irrespective of genotype, is an unrecognized mechanism underlying HFpEF. It was reported wild-type TTR might be an underdiagnosed cause of HFpEF. However, the prevalence of wild-type ATTR among patients with HFpEF is not well-established in Taiwan and Asia.~One of the most convenient method to detect and diagnosis cardiac amyloidosis is 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy6. In the study of Gonzalez-Lopez et al, in 120 HFpEF patients, 16 (13.3%) had positive 99mTc-DPD scan6. Four patients with positive 99mTc-DPD scan received endomyocardial biopsy and confirmed cardiac amyloid deposition6. In addition, technetium-99m TC pyrophosphate (PYP) scintigraphy is also very useful in diagnosis of cardiac amyloidosis.~The propose of this study is to determine the prevalence of ATTRwt among elderly HFpEF patients in Taiwan. In this study, the investigators will recruit a cohort of HFpEF patients in Taiwan to define the number of patients who have cardiac amyloidosis by utilizing highly sensitive heart imaging and blood tests. The investigators will also explore differences in different risk factors as they relate to heart failure disease progression in cardiac amyloidosis. According our previous studies, the average age of HFpEF in Taiwan is 65 y/o. In this study, the investigators set age limitation as 60 y/o. However, because 5% ATTRwt were < 60 y/o9, therefore, the investigators also recruit patients >50y/o with risk factors of ATTRwt.~Hypothesis HFpEF is a heterogeneous clinical situation with multiple underlying causes. ATTRwt is an underdiagnosed cause of HFpEF but the prevalence is unknown in Taiwan. ATTRwt can be diagnosed non-invasively by 99mTc-PYP scintigraphy7. The investigators aimed to investigate the prevalence and clinical characteristics of ATTRwt among patients with HFpEF.~Primary Objective(s) / Endpoint(s) Percentage of participants with ATTRwt among patients with HFpEF in Taiwan~Secondary Objective(s) / Endpoint(s) To investigate the clinical and echocardiographic characters in ATTRwt patients and compare with HFpEF patients without ATTRwt~Trial Population Eligible HFpEF patients with a LVEF of ≧50%, New York Heart Association (NYHA) class I-IV symptoms: Both in-patients or patients in clinics could be enrolled. These patients could be newly diagnosed or has been diagnosed. Study subjects will be pre-stratified according to left ventricular posterior wall thickness (LVPW) ≥12mm or less; number of subjects with LVPW ≥12mm should account for more than 50% of total subjects recruited in the final analysis.~Sample Size and Sample Size Justification The study will prospectively evaluate the prevalence of ATTRwt among patients with HFpEF. Assume the expected 10% prevalence of ATTRwt in patients with HFpEF, the target recruitment of 260 HFpEF patients would yield 25 ATTRwt positive result, which would provide the prevalence estimate with associated 90% confidence interval at the range of +- 3%. The estimated enrolled time is 18 months.~Key Inclusion Criteria~Patient is ≥ 60 years old or 50 y/o with carpal tunnel syndrome or spinal stenosis~Patient has been diagnosed as HFpEF in their medical history or newly diagnosed as HFpEF. They have HF symptoms with NYHA Classification of I-IV when diagnosis. The criteria of HFpEF is according to our previous studies10.~More than 50% of them have LVPW ≥12mm (when diagnosis).~Written informed consent could be obtained~Key Exclusion Criteria~Patients unwilling to join this projects~Patients with unstable coronary artery disease, plan to receive coronary intervention within months.~Patients has previous history of heart failure reduced ejection (HFrEF) with a LVEF <40%.~Method~Patients recruitment and study protocol The enrolled and exclusion criteria were mentioned above. The investigators will enroll 260 HFpEF patients (> 50% with LVPW thickness >12mm). After receiving informed consent, patients will receive NTproBNP, ECG, and echocardiography. Then the investigators will arrange 99mTc-PYP scan to detect the presence of amyloidosis. If patients have these data (ECG, NTproBNP, echocardiogram, 99mTc PYP) within 6 months, the investigators will record and use this data and do not perform again. In patients with positive 99mTc-PYP scan, the investigators will detect urinary monoclonal light chain and serum monoclonal light chain. In addition, the investigators will arrange TTR genetic testing.~Data Collection Delegated physicians or study personnel blinded to scintigraphy results will review the medical records of all patients. Demographic and clinical data will be collected during outpatient clinic visit.~Scintigraphy Protocol Planar and single-photon positive emission computed tomography (SPECT) imaging with 99mTc-PYP was performed with a dual head Philips Precedence SPECT/CT camera (Philips Healthcare, Guildford, United Kingdom). Patients received 20 to 25 mCi of 99mTc-PYP intravenously and images were obtained at 2 hours over 8 minutes duration.~Genotype Testing The TTR mutation was confirmed by sequencing of the TTR gene following National Taiwan University Hospital established protocols. All 4 exons and their flanking intron regions of the human TTR gene were amplified by polymerase chain reaction (PCR). The amplicons were purified by the Gel/PCR DNA Fragments Extraction Kit (Geneaid, Taipei, Taiwan). Sequencing was performed at the corresponding exons by using the ABI3730 automatic DNA sequencer (Applied Biosystems, Foster City, CA).

Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure cases with heterogenous cause and variable presentations. The diagnosis of HFpEF required clinical signs and symptoms of HF, normal left ventricular ejection fraction (LVEF) and evidence of diastolic dysfunction. No treatment has been shown in recent major clinical trials having benefits in these patients. One major reason of the poor response to medical treatment is the heterogeneity of HFpEF, which contains many different underline causes. To identify the underlying causes of HFpEF may improve the diagnosis and treatment in these patients.~Age-related amyloid deposition has first been reported in 1876 and the following autopsy studies showed the prevalence of senile cardiac amyloid is up to 25%. Recently, it has been recognized that the deposits in senile cardiac amyloid are derived from wild-type transthyretin (TTR). Transthyretin amyloidosis cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin protein. There are 2 types of ATTR classified by genetic mutation including wild-type ATTR (ATTRwt) and familial cardiac amyloid caused by TTR mutation (ATTRm).~Multimodality techniques have been developed to assist in the diagnosis of the diagnosis of TTR. Among them, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy is a non-invasive test and it can diagnose TTR from other cause diverse form of cardiac amyloidosis and cardiomyopathy. In the study of Gonzalez-Lopez et al, in 120 HFpEF patients, 16 (13.3%) had positive 99mTc-DPD scan. Four patients with positive 99mTc-DPD scan received endomyocardial biopsy and confirmed cardiac amyloid deposition.~ATTRwt could be an important cause of HFpEF and it was often under diagnosed. A recent study in Spain reported that 13% of patents over age of 60 years with HFpEF and left ventricular wall thickness of 12mm or more had ATTRwt. However, the prevalence of ATTRwt among patients with HFpEF is not well-established in Taiwan and Asia. The aim of this study is to determine the prevalence, clinical characteristics, risk factors and outcomes of ATTRwt related HFpEF patients in Taiwan.

African Americans living with chronic medical conditions are at high risk for depression and other mental health disorders yet are less likely to be diagnosed or receive treatment than their white counterparts. Left untreated, depression can increase disease severity and risk for mortality. One especially vulnerable group is patients with sickle cell disease (SCD), a genetic blood disorder that primarily affects people of African descent and disproportionately impacts those living in disadvantaged circumstances. Sickle cell causes severe acute and chronic pain, end-organ damage, and early mortality. In SCD, the transition from adolescence to adulthood is a tumultuous period, characterized by social vulnerability, increased medical complications, and high health care utilization. Young adults in this age group, 16-30, are at high risk for mental health disorders and suicide.~Using mobile technology, the investigators can provide high-quality, evidence-based behavioral mental health treatment that reaches patients in under-resourced settings. Digital cognitive behavioral therapy (CBT), also known as computerized CBT, is effective for treating depression and anxiety, and can be easily brought to scale at low cost. Several meta-analyses have found digital CBT effective for treating depression and anxiety in white adults. The investigators' group has shown in a large-scale trial that it is effective for treating these symptoms among African American patients at 22 primary care clinics. In two adult sickle cell clinics, the investigators have shown that routine mental health screening and digital CBT delivered as part of usual care can improve depressive symptoms and daily pain among adults with SCD. The investigators' group has also used this method to treat pain in pediatric SCD patients.~Gap in evidence: Despite the promise of digital CBT, there are barriers to widespread use of this technology, particularly in low-resource settings serving minorities. Studies using digital CBT often suffer from high attrition and poor adherence. In real-world settings, uptake is poor even when the service is offered free of charge. These limitations affect patients living with SCD. The investigators will modify how a digital CBT program for mental health is delivered to these patient sat the patient, provider, and organizational levels, by adding references and content representing SCD, chronic pain, and stressors unique to African Americans. The investigators believe this approach will radically improve the implementation of mental health screening and treatment in low-resource settings such as clinics and community organizations serving adolescents and adults with SCD, and similar communities.~Strategy and goals: Population-and setting-specific adaptations to interventions can lead to their successful implementation and wider use, yet no studies show how much adaptation is needed to effectively implement digital CBT in different settings. Qualitative data from The investigators' group and others show that cultural factors-lack of relatability, representation, and perceived stigma regarding mental health treatment-limit engagement with digital CBT programs. The investigators' proposal will devise changes to advertising, promotion, and health coach communications, that will decrease stigma and make digital CBT more relatable and relevant to young adults with SCD. The investigators hypothesize that low-cost adaptations to a digital CBT program will have better engagement than digital CBT with standard implementation strategy.~Aim 1: Use implementation science (ImS) and human-centered design methods to define the barriers to delivering routine mental health screening and digital CBT to adolescents and young adults with SCD. By leveraging ImS theory, models, and frameworks, The investigators will systematically collect and analyze qualitative data to define and understand the problem, stakeholder needs, and cultural barriers to routine mental health screening and treatment in SCD clinics and the community. Specifically, the investigators will use the Behavior Change Wheel as a validated method for identifying the appropriate behavior change and implementation strategies.~Aim 2: Rapidly iterate, test, and evaluate adaptations to the implementation strategy for a coach-enhanced digital mental health service. Based on findings from Aim 1, the investigators will systematically develop, test, and evaluate changes to how the CBT program is advertised/promoted, and introduced to patients and providers. The investigators will tailor the messages and multimedia content that health coaches send to patients.~Aim 3: Demonstrate that a population-specific implementation strategy improves engagement with a digital CBT-based mental health service. The investigators will recruit 40 adolescents and young adults with SCD (ages 16-30) and comorbid depression and randomize them to either the off-the-shelf digital CBT program and standard implementation strategy that has no content or references to SCD, chronic pain, or the unique challenges facing minority groups, to adapted digital CBT with a SCD-specific implementation approach.~Addressing mental health in SCD is a major step to delivering quality care and improving outcomes for this, and other hard-to-reach, minority populations. This study will generate the necessary data and infrastructure to conduct a large scale, R01-funded, multi-site pragmatic trial to determine how digital CBT can be used as an effective, low-cost, and scalable mental health treatment for adolescents and young adults with SCD.

African Americans living with chronic health conditions are more likely to experience depression and other mental health disorders than their healthy counterparts, and are more likely to experience severe depression than whites, but less likely to be diagnosed or receive treatment. One especially vulnerable group is patients with sickle cell disease (SCD), a genetic blood disorder that primarily affects people of African descent, many of whom live in disadvantaged circumstances and are cared for in under-resourced settings. SCD causes severe acute and chronic pain, end-organ damage, and early mortality. Patients transitioning from adolescence to adulthood (ages16-30) are at high risk for mental health disorders and suicide.~Using mobile technology, the investigators can provide high-quality, evidence-based behavioral mental health treatment that reaches patients in different settings. Digital cognitive behavioral therapy (CBT) is effective for treating depression and anxiety and can be brought to scale at low cost. Despite the promise of digital CBT, there are barriers to its widespread use, particularly in low-resource settings serving minorities. Qualitative data show that cultural factors-lack of relatability, representation, and perceived stigma regarding mental health treatment-limit engagement with digital CBT programs. Population-and setting-specific adaptations to interventions can lead to their successful implementation and wider use. The investigators will work with a digital CBT program to decrease stigma and make it more relatable and relevant to young adults with SCD, by devising changes to advertising and promotion, and tailoring communication with an integrated health coach, Aim 1: Use implementation science (ImS) and human-centered design methods to define the barriers to delivering routine mental health screening and digital CBT to adolescents and young adults with SCD. Aim 2: Rapidly iterate, test, and evaluate adaptations to the implementation strategy for a coach-enhanced digital mental health service. Aim 3: Demonstrate that a population-specific implementation strategy improves engagement with a digital CBT-based mental health service.~The investigators will capitalize on our mobile technology tools, interdisciplinary expertise, and community-based partnerships to investigate the implementation of digital CBT into low-resource clinics and community-based organizations serving adolescents and adults with sickle cell disease.

Obesity is associated with increased mortality and morbidity and represents a worldwide epidemic that is increasing in prevalence and remains a significant problem in Canada and a burden on our healthcare system. Maintaining long-term weight loss is the Achilles' heel of obesity therapy. Treatment for obesity with surgery is increasing because it has been shown to produce the best results for long-term weight loss and improving obesity related risk factors and diseases. But, these benefits are often reduced by inadequate weight loss or by weight regain in many patients after surgery.~Contrave (naltrexone HCl and bupropion HCl) extended-release tablet is an approved drug and indicated to be used with a low calorie diet and increased physical activity for chronic weight management in obese adults (BMI 30 Kg/m2 or greater) or overweight adults (BMI 27 Kg/m2 or greater) with at least one weight related condition such as hypertension or diabetes. It is unknown how many or which medical treatments for weight loss, such as Contrave work in the subjects who have had bariatric surgery.~This is a 1 year, phase 4, prospective, randomized, double-blind, placebo controlled study that will be conducted across multiple Bariatric Centres of Excellence (BCoE) in Ontario. Consenting participants will be randomly assigned to receive Contrave with usual care (dietary and behaviour counselling) or placebo with usual care. All subjects will also continue to receive usual care. The study includes several follow up visits to assess safety and treatment effects, some in person and others by telephone or video conferencing. Body weight, blood pressure, heart rate, waist circumference, lab tests, and subject completed questionnaires will be collected as part of usual care or for the study. Changes in medications and any possible side effects will also be monitored during the study.~To qualify, men and women must have had prior bariatric surgery (roux en-y gastric bypass or sleeve gastrectomy) at a surgical Center of Excellence within the Ontario Bariatric Network, and have inadequate weight loss or significant weight regain, based on the following OBN criteria:~< 10% total body weight (TBW) loss at 6 months or;~< 20% TBW loss at 12 months or;~Weight regain of > 25% of weight loss.~The aim of this study is to explore the effectiveness of Contrave combined with usual care (dietary and behaviour counselling) compared to placebo with usual care, in patients who have inadequate weight loss or significant weight regain following bariatric surgery.

Contrave (naltrexone HCl and bupropion HCl) extended-release tablet is an approved drug and indicated to be used with a low calorie diet and increased physical activity for chronic weight management in obese adults (BMI 30 Kg/m2 or greater) or overweight adults (BMI 27 Kg/m2 or greater) with at least one weight related condition such as hypertension or diabetes. It is unknown how many or which medical treatments for weight loss, such as Contrave work in the subjects who have had bariatric surgery.~The purpose of this study is to explore the effectiveness of Contrave combined with usual care (dietary and behaviour counselling) compared to placebo with usual care, in patients who have inadequate weight loss or significant weight regain following bariatric surgery.

This is a biological study for adult MDS patients who undergo HSCT procedure.The research is focused on the study of biological mechanisms of disease relapse after HSCT in MDS to provide the rationale to develop pre-emptive strategies in patients with high risk of transplant failure.~Viable bone marrow samples will be collected and cryopreserved from MDS patients before transplantation and at clinical disease recurrence.~CD34+ blast cells at disease relapse after HSCT will be compared with CD34+ cells collected before transplant by using Single-cell sequencing.~To study genomic and transcriptomic changes in CD34+ blast cells at disease relapse after HSCT will be used TARGET-seq in parallel with unbiased whole-transcriptome analysis.

This is a biological study for adult MDS patients who undergo HSCT procedure. Viable bone marrow samples will be collected and cryopreserved from MDS patients before transplantation and at clinical disease recurrence. CD34+ blast cells at disease relapse after HSCT will be compared with CD34+ cells collected before transplant to study genomic and transcriptomic changes.

The main purpose of this study is to assess the efficacy of TAS-205 in patients with Duchenne muscular dystrophy (DMD) compared with placebo as measured by the mean change from baseline to 52 weeks in the time to rise from the floor． Following completion of the treatment period, patients may elect to continue in open-label extension study.

The purpose of this study is to evaluate the efficacy and safety of TAS-205 in patients with Duchenne muscular dystrophy

Laparoscopic cholecystectomy is one of the most common performed procedures of general surgery. Although it is performed with minimally invasive techniques, postoperative pain can be moderate to severe, requiring administration of large doses of opioids perioperatively in combination with other categories of analgesics in order to be relieved. Modern anesthesiology practices tend to limit the opioids administered to patients due to a variety of complications observed, specifically in certain populations (obese, elderly) and also due to the opioid crisis appearance in United States and in many European countries. As such, multimodal analgesia and opioid limitation is the cornerstone of modern perioperative pain management.~Peripheral nerve blocks and especially trunk blocks can play a significant role when confronting perioperative pain. Erector spinae Plane Block (ESPB) is a novel trunk block first described in order to relieve thoracic neuropathic pain. Since then, it was performed by anesthesiologists for chronic pain, acute post traumatic pain and in a wide variety of surgical procedures for postoperative analgesia.~There are no trials that study the efficacy of adding dexmedetomidine as an adjuvant to the local anesthetic in order to ameliorate the quality and extend the duration of the Erector Spinae Plane Block.~This trial is a randomized, controlled, double - blind, prospective trial, aiming at assessing the efficacy of bilateral Erector Spinae Plane Block (ESPB) in managing perioperative pain in patients who undergo elective laparoscopic cholecystectomy. In this trial, 60 patients (men and women), aged 18 to 70 years old that will undergo laparoscopic cholecystectomy which will be performed by the same experienced, surgical team, will be recruited.~Patients will be randomized into three groups, Group D (Ropivacaine plus dexmedetomidine group), Group R (Plain Ropivacaine group) and Group C (Control group).~The solutions that will be administered during the performance of ESPB, will be prepared by an independent anesthesiologist. The ultrasound image during the performance of ESPB, as well as the complications that may arise after the performance of the block, will be recorded.~The age, sex, American Society of Anesthesiologists (ASA) classification, height and weight of the participants, will be recorded.~After the induction of general anesthesia [propofol (2-3 mg/kg), fentanyl (2-3 γ/kg), rocuronium (0,6 mg/kg)], general anesthesia will be maintained with desflurane titration. In all patients, remifentanil infusion will be titrated in order to achieve intraoperative analgesia (Systolic Arterial Blood Pressure within the 20% of Baseline Systolic Blood Pressure). In all patients Paracetamol 1000 mg and Tramadol 100 mg will be administered, 30 minutes before the end of surgery. During surgery, vital signs, remifentanil infusion or other drugs that will be administered, will be recorded. At the end of surgery, Train of Four stimulation will be performed and in the presence of remaining neuromuscular blockade, sugammadex will be administered in the proper doses.~In all patients, post - operative analgesia will be offered with a Patient controlled Analgesia (PCA) pump, containing morphine. Lock - out period will be 10 minutes and the morphine dose will be 20 mcg/kg, without continuous infusion.~The duration of stay of the patient in Post Anesthesia Care Unit (PACU), will be recorded as well as the Aldrete Score and the vital signs the moment the patient leaves the PACU.~Postoperative pain will be recorded at arrival and discharge of the patient from the PACU, as well as 3, 6, 12 and 24 hours after the end of surgery, according to NRS pain scale. All patients will receive Paracetamol 1000 mg x 3 (iv) at the surgical ward.~Post - operative nausea and vomiting, morphine consumption and the vital signs of the patients will be recorded 3, 6, 12and 24 hours after surgery. The mobilization time, hospitalization time, as well as the satisfaction score of the patient in a scale from 1 to 6, 24 hours after the end of surgery will be recorded.

The aim of the trial is to study the efficacy of bilateral Erector Spinae Plane Block (ESPB) in managing perioperative pain in patients who undergo elective laparoscopic cholecystectomy

Urinary tract infections (UTI) are common in infants. The diagnosis of a UTI has important implications for follow-up, and delayed treatment can result in morbidity, including renal scarring and serious bacterial infection.~Obtaining urine from pre-continent children can be difficult and time consuming, the method of collection must balance reliability, speed, low rate of contamination, and invasiveness The actual guidelines recommend suprapubic aspiration or bladder catheterization for collection of urine sample in pre-continent children, but these methods are invasive.~The most common way to collect urines in infants is the use of a sterile collection bag. This is an easy technique, but time consuming and responsible for high rate of contamination, leading to false positives.~According to the American Academy of Pediatrics, midstream clean-catch urine is an acceptable method to diagnose urinary tract infection. However, it is impractical in pre-continent children.~Recently, two quick, safe and effective methods have been reported in the literature:~The Quick-wee method: it consists in stimulating the suprapubic area with a cold and wet compress to obtain urines.~The bladder stimulation method: the child is held under the armpits with legs dangling and a physician taps the suprapubic area and massages lumbar area alternatively.~However, advanced age, high weight, and level of discomfort during bladder stimulation were significantly associated with failure to obtain urines.~Futhermore, even if urine collection in pre-continent children most often concerns urinary tract infections, these techniques could also be used to look for a metabolic abnormality, an uropathy or a nephropathy (urine electrolyte concentrations, proteinuria, hematuria).~The aim of the study is to compare the effectiveness of two non-invasive midstream urine collection methods in pre-continent children : the Quick-Wee method and the Bladder stimulation method.~The investigators will also compare in the two groups the time required to obtain urine sample, the comfort of the infant during urine collection and the quality of urines.~Finally, for each technique will be analyzed the risk factors associated with failure in obtaining urine sample

Urinary tract infections are common in infants. Obtaining urine from pre-continent children can be difficult and time consuming. The method of collection must balance reliability, speed, low rate of contamination, and invasiveness.~According to the American Academy of Pediatrics, midstream clean-catch urine is an acceptable method to diagnose urinary tract infections. However, it is impractical in pre-continent children.~Recently, two quick, safe and effective methods have been reported in the literature:~The Quick-wee method: it consists in stimulating the suprapubic area with a cold and wet compress to obtain urines.~The bladder stimulation method : the child is held under the armpits with legs dangling and a physician taps the suprapubic area and massages lumbar area alternatively.~However, advanced age, high weight, and level of discomfort during bladder stimulation were significantly associated with failure to obtain urines.

Participants with lung adenocarcinoma underwent contemporaneous 18F-FDG and 68Ga-FAPI PET/CT for an initial assessment. Tumor uptake was quantified by the maximum standard uptake value (SUVmax). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 18F-FDG and 68Ga-FAPI PET/CT were calculated and compared to evaluate the diagnostic efficacy. In addition, the investigators further investigate the performance of 68Ga-FAPI PET/CT for differentiating invasive adenocarcinoma from adenocarcinoma in situ (pre-invasive lesion) or minimally invasive adenocarcinoma in participants with solitary ground-glass opacity nodules.

To evaluate the potential usefulness of 68Ga-FAPI positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in lung adenocarcinoma, compared with 18F-FDG PET/CT.

A large amount of people with stroke face extensive changes to live an active life and restrictions in engaging in various activities are common. However, the rehabilitation seldom focusses on the process of change people with stroke need to go through to adapt to their changed capacity and reach an active life on new terms. This implies that rehabilitation needs to be developed to provide activity-based self-management strategies that can facilitate an active life. Also, there is a need to improve the access to rehabilitation by making use of digital e- health solutions. Based on these needs, the web-based occupational therapy intervention Strategies Empowering activities in Everyday life (SEE 1.0) has been developed.~This feasibility trial has a pre-test post-test design without a control group. The trial is embedded in a mix- method approach combining assessment tools, feasibility registration forms, intervention logbooks, qualitative interviews and focus groups. The feasibility of the web-based intervention SEE as well as of the study design, will be evaluated in terms of acceptability, adherence, values and appropriateness from the perspectives of patients with stroke and the staff. Also, the potential outcome of SEE will be evaluated quantitatively and qualitatively.~The results will support the continued development of SEE and provide for larger-scale research studies. The intervention, that combines a focus on empowering an active everyday life with a web-based format including online meetings, is innovative and is not part of clinical practice today. Thereby, the results can be valuable for future research and clinical practice in general. The study protocol and the results will be published in peer-reviewed scientific journals and presented at conferences.

The purpose of the study is to evaluate the feasibility and potential outcomes of a first version of a web-based intervention in occupational therapy focusing on empowering an active everyday life for people with stroke.

Immune thrombocytopenia is an autoimmune disorder characterized by formation of autoantibodies against platelet antigens leading platelet destruction.~Corticosteroids increase the platelet count in about 80 percent of patients. However, many patients have a relapse when the dose of corticosteroid is reduced. Debilitating side effects are common in patients who require long-term corticosteroid therapy to maintain the platelet count. Romiplostim, it is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin, has been shown to be effectively raise the platelet count in adult patients (aged 18 years and over) who have had their spleen removed or where splenectomy is not an option and have received prior treatment with corticosteroids or immunoglobulins, and these medicines did not work (refractory ITP). There are a few case reports where romiplostim an option as first line treatment for IT.~The purpose of this study is to determine the response rate and response duration with the combination of rituximab (100 mg weekly four weeks), romiplostim (2mcg/Kg four weekly) and high-dose dexamethasone (40mg PO days 1-4) in untreated adult patients with <30*109/L platelet count diagnosed with immune thrombocytopenia.~A complete response is defined as an increase in platelet counts to >150×109/L on two consecutive occasions. A clinical response is defined as an increase in the platelet count between >30×109/L on two consecutive measures and no bleeding. Duration of response is considered from the day of the initial administration to the first time of relapse (platelet count <30×109/L) or to time of analysis Patients will be evaluated each week during 4 weeks and then every month for at least 6 months.

The purpose of this study is to determine the response rate and response duration with the combination of low-dose rituximab, romiplostim and high-dose dexamethasone.

This observational case-control study will be conducted at the Department of Obstetrics and Gynecology, Cengiz Gokcek Public Hospital, Gaziantep, Turkey, between October 2020 and October 2021. The protocol was approved by the Ethics Committee for Clinical Research of Gaziantep University (reference no: 2020/276). The study strictly will be adhered to the principles of the Declaration of Helsinki. All subjects will be included in the study gave oral and written informed consent. Membrane rupture before labor and before 37 weeks of gestation is referred to as preterm premature rupture of membranes (PPROM). Every woman in the study population will be undergone obstetric ultrasound examination and fetal-maternal assessment will be carried out. The blood for analysis will be firstly obtained in maternal blood on the day of diagnosis at the study group. Healthy subjects who had a normal pregnancy and outcomes without any fetal-neonatal complications will be accepted into the control group. Forty-four gestational age-matched healthy pregnant women who will be delivered at term will be included in the study as the control group. In the control group, the pregnant women will be taken the maternal blood at the admission day. The women in both groups will be observed until the delivery and perinatal data will be noted. All The participants with PPROM will be also hospitalized. Then, the protocols for pregnant women with PPROM in our hospital are as follows: All patients with PPROM are hospitalized and expectant protocol is applied. After hospitalization until the delivery of baby, all pregnant women with PPROM receive prophylactic antibiotics for 1 week and betamethasone injection. The non-stress test and fetal movement determined by the mother are used for the detection of fetal well-being. The signs for clinical chorioamnionitis such as uterine tenderness, fever, purulent discharges from the cervical canal and inflammatory markers like white blood cell count (WBC) and C-reactive protein (CRP) levels are monitored carefully during the hospitalization. After a latency period, PPROM pregnancy will gone to spontaneous delivery or will be applied termination procedure. In the study group, the placenta will be stained with hematoxylin-eosin and will be examined under a light microscope for histological signs of neutrophil infiltration and chorioamnionitis. Then, this study will be determined maternal serum melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 levels in women with PPROM(n=44) compared to those of volunteer healthy pregnant women (n=44). Then, these three markers levels at maternal serum and cord serum will be evaluated for histological chorioamnionitis and maternal/neonatal outcomes in the study group.

Introduction: To evaluate the maternal blood serum melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 levels in pregnant women complicated by preterm premature rupture of membranes (PPROM) and to compare the results with healthy pregnancies. In addition, to determine whether maternal/umbilical cord blood concentrations of melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 are of value in the diagnosis of histological chorioamnionitis in patients with preterm premature rupture of membranes (PPROM).~Methods: This cohort study will be included 44 pregnant women with PPROM and 44 gestational age-matched healthy subjects in 24-32 weeks of pregnancy. The blood for analysis will be firstly obtained in maternal blood on the day of diagnosis at the study group. Healthy subjects who have a normal pregnancy and outcomes without any fetal-neonatal complications will be accepted into the control group. Forty-four gestational age-matched healthy pregnant women who will be delivered at term will be included in the study as the control group. In the control group, the pregnant women will be taken the maternal blood at the admission day. The women in both groups will be observed until the delivery and perinatal data will be noted. Then, the blood for analysis will be secondly obtained in maternal blood during termination of the pregnancy (or spontaneous labor) at the study group. Lastly, the blood for analysis will be also obtained in umbilical cord blood at the study group. These three markers levels will be measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The placenta will be sent to histological examination in the study group. These three markers levels in women with PPROM will be compared to those of volunteer healthy pregnant women. In the study group, these three markers levels at maternal serum and cord serum will be evaluated for histological chorioamnionitis and maternal/neonatal outcomes.

Trauma can cause many injuries, some of which are life-threatening and require treatment in an intensive care unit (ICU). Despite best available treatment and therapies, people who sustain a critical traumatic injury are at greater risk of death or long-term disability. From 2010 to 2015, approximately 9% of people admitted to an ICU in Australia and New Zealand for treatment of their injuries, did not survive. In Victoria, 6-months post injury, approximately 31% of people who were critically injured developed severe disabilities or died.~Following a traumatic injury, a number of complex pathways are activated by the body. These pathways can occur over hours or weeks and may lead to damage of cells, tissues or blood vessels and may destroy other healthy tissue. The treatment of traumatic injury focuses on trying to minimise further damage that can occur after the initial injury.~Erythropoietin is a glycoprotein hormone essential for erythropoiesis and was first purified in 1977. Its human recombinant analogues known as erythropoiesis stimulating agents (ESAs) are approved for human therapeutic use. However, erythropoietin is also a pleiotropic cytokine with effects beyond just erythropoiesis. Studies in animals have demonstrated the potential protective effects of erythropoietin to organs including the brain, kidney, liver and heart, and anti-inflammatory properties.~Previous research suggests the use of the ESA called epoetin alfa, increases the number of patients surviving severe trauma and reduces the risk of disability in those who survive.~The primary aim of the study is to determine the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients.~2500 mechanically ventilated ICU patients admitted with a primary trauma diagnosis presenting to the ICU will be recruited into the study from participating study centres in Australia, New Zealand, Europe, and Saudi Arabia.

The EPO-TRAUMA study is a prospective, multi-centre, double-blind, phase III, randomised controlled trial evaluating the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients.~2500 mechanically ventilated ICU patients admitted with a primary trauma diagnosis presenting to the ICU will be recruited into the study from participating study centres in Australia, New Zealand, Europe, and Saudi Arabia.

Identification of T cell inhibitory signals, including PD-1/L1, has prompted the development of a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. However, elimination of cancer by T cells is only one step in the cancer-immunity cycle, which enable providing several therapeutic targets and tailoring of combinations of immune therapies. SHR2150 is a small molecule agonist of toll-like receptors (TLRs) 7 designed to activate antigen-presenting cells and functions as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I/II, dose escalation/expansion study of a combined regimen of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. This study is designed to assess the safety, tolerability, RP2D and clinical efficacy of this regimen.

This phase I/II trial aims to evaluate safety and efficacy of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody in subjects with unresectable/ metastatic solid tumors. Patients will receive the combined regimen in 3-week treatment cycles. During the Phase 1 dose escalation portion of the trial, three oral doses of SHR2150 will be combined with intravenous administration of chemotherapy and PD-1 or CD47 antibody. In the Phase 2 dose expansion portion, patients will be treated with the Recommended Phase 2 Dose (RP2D) of SHR2150 in combination with chemotherapy plus PD-1 or CD47 antibody.

Blood transfusion is at the heart of the therapeutic arsenal when one wishes to preserve the hemodynamic balance of a patient. There are two types of transfusion: the homologous one (blood from a compatible donor) and the autologous or autotransfusion method (which is done with one's own blood / by the patient's own blood).~Although homologous transfusions can save lives, it may lead to non-negligible adverse events. Among these events, immunological consequences such as allo-immunization against red blood cells' antigens from the donor blood can be cited. Some infections have also been reported following allogenic transfusions.~Since then, multiple solutions have been developed to avoid exposing patients to these risks. It is in this context that was born the Patient Blood Management (PBM). Thus, the strategy in this PBM has been defined as the appropriate use of blood and blood components, with the aim of minimizing the use of allogeneic transfusions. In this context, particular interest has been given to autologous transfusion or autotransfusion or cell salvage.~The principle of Intra-Operative Cell Salvaged (IOCS) allows intravenous administration of the patient's own blood collected at the surgical site or postoperative wound during hemorrhagic surgery. It is used mainly in cardiac, vascular, transplant and elective orthopedic surgeries and tends to spread to other surgeries such as neurosurgery, obstetrics and urology.The IOCS has multiple benefits, primarily autologous (the patient gets his own blood), immediate availability in the operating room, reduced costs of patient care, and the recycling of otherwise lost blood products. It is part of blood saving techniques that avoid the use of homologous blood. Indeed, the general purpose of IOCS is to reduce (or even stop) the use of allogeneic products and to reduce the risks associated with the ABO compatibility system, as well as all the adverse effects associated with allogeneic plasma and platelet transfusions~Most autotransfusers available on the market operate by centrifugation. Autotransfusion is already a solution in Patient Blood Management and its efficiency and safety have already been optimized. However, there is still a need to improve the quality of the treated blood with an easier-to-use device that could improve the quality of the blood concentrate.~Indeed, with the current devices, it may happen that the use of allogeneic transfusions, plasma and platelets transfusions, is necessary in addition to autologous red blood cells thus reducing the interest of autotransfusion.~It is in this context that i-SEP has developed a new autotransfusion device based on a filtration method. Unlike competing devices, the i-SEP device allows the concentration of not only red blood cells (as competitive devices) but also platelets.~In this study, the i-SEP device is used in typical clinical applications of autotransfusion: cardiovascular and orthopedic surgeries, where there is a risk of hemorrhage and/or blood loss for example ≥ 500mL in cardiac surgery and ≥ 300mL in orthopedic surgery.~The study includes a screening phase (≤ 21Days), surgery phase when the i-SEP device is used (Day 0), a post-surgery phase (Day 1 - Day 6), a first follow-up visit (Day 7 ± 3) and a second follow-up visit (Day 30 ± 7).

Blood transfusion is at the heart of the therapeutic arsenal when there is a hemorrhage and/or blood loss during a surgery. There are two types of transfusion: the homologous one (blood from a compatible donor) and the autologous or autotransfusion method (which is done with the patient's own blood).~Although homologous transfusions can save lives, it can cause significant adverse events. Since then, multiple solutions have been developed to avoid exposing patients to these risks. It is in this context that was born the Patient Blood Management (PBM). Thus, the strategy in this PBM has been defined as the appropriate use of blood and blood components, with the aim of minimizing the use of allogeneic transfusions.~In this context, particular interest has been given to autologous transfusion or autotransfusion or cell salvage, the general purpose is to reduce (or even stop) the use of allogeneic products and to reduce the risks associated with the ABO compatibility system, as well as all the adverse effects associated with allogeneic plasma and platelet transfusions.~Most autotransfusers available on the market operate by centrifugation. Autotransfusion is already a solution in Patient Blood Management and its efficiency and safety have already been optimized. However, there is still a need to improve the quality of the treated blood with an easier-to-use device that could improve the quality of the blood concentrate.~Indeed, with the current devices, it may happen that the use of allogeneic transfusions, plasma and platelets transfusions, is necessary in addition to autologous red blood cells thus reducing the interest of autotransfusion.~It is in this context that i-SEP has developed a new autotransfusion device based on a filtration method. Unlike competing devices, the i-SEP device allows the concentration of not only red blood cells (as competitive devices) but also platelets.~In this study, the i-SEP device is used in typical clinical applications of autotransfusion: cardiovascular and orthopedic surgeries, where there is a risk of hemorrhage and/or blood loss for example ≥ 500mL in cardiac surgery and ≥ 300mL in orthopedic surgery.~The study includes a screening phase (≤ 21Days), surgery phase when the i-SEP device is used (Day 0), a post-surgery phase (Day 1 - Day 6), a first follow-up visit (Day 7 ± 3) and a second follow-up visit (Day 30 ± 7).

Introduction/Background~Findings from an ongoing improvement project to improve antibiotic prescribing for children and adolescents for three acute respiratory tract infections (ARTIs: upper respiratory tract infection, acute bacterial sinusitis, and acute otitis media) among pediatric and family medicine clinics revealed performance gaps between the two primary care specialties. An improvement project was then set up to address the lower performance by family medicine clinics.~Literature review revealed that, in general, quality improvement feedback was more effective if provided to individual clinicians rather than to a group of clinicians, but very limited data existed for antibiotic prescribing practices actually comparing individual clinician feedback to group (clinic-level) feedback.~The hypothesis is that individual clinician data feedback is superior to group (clinic-level) feedback in improving antibiotic prescribing for ARTIs in children and adolescents by family medicine clinicians.~The aim is to determine if there are significant differences for antibiotic prescribing for ARTIs and for broad spectrum antibiotic prescribing percentage between an intervention group and a comparator group of family medicine clinics after the intervention starting November 2015 and ending December 2018.~Methods~Design~A cluster randomized trial was designed for all 98 family medicine clinics within Novant Health Medical Group. In August 2015, retrospective review of data from January 1, 2014 was conducted by the antimicrobial stewardship team, and the trial was developed. Clusters were a subset of clinics identified as under-performing, based on not avoiding antibiotics in at least 83% of patients with upper respiratory infection or common cold (URI) (2013 Healthcare Effectiveness Data Information Set mean in patients 3 months-18 years of age). Among these 47 clinics, 6 had recorded < 20 encounters in the 6 months, January-June 2015, for an illness diagnosis of URI and were excluded.~The remaining 39 clinics sites in 26 practices (1 practice had 10 clinic sites and a second had 5 sites; all others were single site practices) agreed to participate and were stratified by size of clinic (number of clinics or clinicians as very small, small, large, very large). Clinics were then block randomized with selection of half of each stratum for two groups - an intervention group and a comparator group.~The Institutional Review Board of Novant Health Presbyterian Medical Center granted a waiver of written, informed consent. An email was sent to the lead physicians for the 41 remaining clinics detailing the protocol, and all but two clinics agreed to participate.~Intervention~All 39 clinics received the same multifaceted intervention with one exception. This intervention included:~A one-hour, in-person, educational session, in September-October 2015, with the lead clinician, clinic administrator, and stewardship team physicians describing the project and clinical guidelines for URI, ABS, and AOM.~A tip sheet detailing how to improve scores (appropriate codes and documentation strategies).~An after-visit summary for clinicians to give to patients and parents discussing antibiotic use and side effects.~A presentation of summary results for all pediatric and family medicine clinics for the 3 ARTI metrics to for the six-month period, January-June 2015. Clinic comparison performance data were then provided monthly for all 39 clinics~Discussion about a new clinical pathway for acute bacterial sinusitis with a request for adoption and implementation.~A request of each practice to:~Discuss the guidelines for the three metrics, the tip sheet, the AVS, and baseline performance at the outset.~Adopt and implement the ABS clinical pathway.~Review monthly the performance scores for the three metrics. The exception was the intervention group received monthly clinician-specific performance data for the three measures, while the comparator group received only clinic-level data. All family medicine clinics received composite clinic-level data for all family medicine and pediatric clinics so each clinician could view, at the clinic level, all other clinics' performances. Clinical decision support was not used.~Data Collection~Baseline performance data were collected retrospectively from January 1, 2014-October 31, 2015. The intervention period was November 1, 2015-December 31, 2017. A post-intervention period was from January 1-December 31, 2018, during which time only clinic-level data were provided monthly to all 39 clinics.~Visit-level data included ICD-9 codes and, starting in October 2015, ICD-10 codes associated with an encounter (IE) and listed as a visit diagnosis. Antibiotic prescribing was determined by medication orders' search in the record associated with the encounter or within 30 days prior (if URI diagnosis) or within 60 days prior (if ABS or AOM diagnosis) and 3 days subsequent to the encounter. IEs were defined as evaluation and management visits for new patients (with codes 99201-99205) and for established patients (with codes 99212-99215).~Measures~Using guidelines from the American Academy of Pediatrics and the Infectious Diseases Society of America, customized clinical quality measures for the 3 ARTIs were developed and validated by selective, manual chart review of electronic health records. These measures represented the primary outcomes at cluster level and included as numerator, appropriate care, and denominator, IE, for each ARTI.~A target of ≥ 90% for URI was set using the HEDIS® 2013 90th percentile, and at 80% for ABS and AOM, consistent with targets suggested by an outpatient antibiotic use target-setting workgroup.~A secondary outcome was broad-spectrum antibiotic prescribing (BSAP) percentage, determined monthly by enumerating all antibiotics given, stratifying by narrow and broad spectrum and dividing by the total number of antibiotics prescribed for any condition, not limited to the 3 ARTIs. For this calculation, patients were excluded if their record showed an allergy to an antibiotic listed as narrow or broad spectrum and/or one of the listed antibiotics had been given 60 days prior.~To determine if code shifting occurred or total antibiotic utilization changed after the intervention began, the investigators recorded the mean number of encounters per clinic for the 3 ARTIs and the total of all IEs and antibiotics prescribed for all patients seen for illness in the baseline and intervention periods in both groups.~Statistical Analysis~Power will be estimated based on the primary outcomes, baseline-to-intervention period change in the proportion of encounters with the appropriate treatment for URI, ABS, and AOM, respectively. The numbers of clusters are fixed at 22 for the intervention group and 17 for the comparator group. Based on retrospective data from the baseline period, the average cluster sizes, i.e., the average numbers of encounters per clinic over 22 months, for URI, ABS, and AOM, respectively, are 210.0, 72.6, and 129.2 for the intervention group and 211.0, 65.5, and 133.6 for the comparator group. This provided > 85% power to detect a study group difference in mean baseline-to-intervention period change of 0.4 standard deviations, corresponding to a medium effect size, with two-sided alpha = 0.05, for intra-cluster correlations (ICCs) ranging between 0.01 and 0.15. The power analysis was performed using PASS 15.~The clinic is the unit of analysis for describing changes in clinical decision making. The primary outcomes, i.e., the proportion of relevant encounters with appropriate treatment (for URI, ABS, and AOM, respectively) will be recorded for each clinic during the baseline and intervention periods.~To assess the influence of the intervention on clinical decision making, a generalized linear mixed model (GLMM) will be analyzed for each outcome using PROC GLIMMIX® in SAS. The response variable in the models is y/n, where y = the number of appropriate treatment occurrences and n = the total number of relevant encounters, and the response distribution is specified as binomial with a logit link. The independent variables are the study group (intervention, comparator), time period (baseline, intervention), a study-group-by-time interaction term, and clinic size (very small, small, large, and very large) (used as the stratification variable in the randomization). The models include a random intercept term for clinic to account for relatedness of clinical decisions made in the same clinic. The p-value for the interaction term will be used to assess significance between the intervention and comparator groups on the baseline-to-intervention period change.~The overall alpha level is pre-specified at 0.05. To account for multiple testing, Holm's Step-Down procedure will be used to adjust p-values, where the family of inferences includes those for the three primary outcomes and the secondary outcome, BSAP%. In the case of a significant interaction effect, the pre-intervention and post-intervention outcome will be compared for the intervention and comparator groups, respectively, using pre-specified contrasts generated from the GLMM. Odds ratios, corresponding to these contrasts, will be calculated, along with 95% confidence intervals that are Bonferroni-corrected (at the α/2 = 0.025 level) to further adjust for multiple comparisons. For each outcome variable, the ICC will be calculated using the level-2 (i.e. random intercept) variance from the GLMM and a level-1 variance component assumed to be π‸2/3 = 3.29 for a logistic random intercept model.~Analysis of the secondary outcome, BSAP percentage, will be conducted using the steps described for the primary outcomes. All analyses will be performed using SAS.

Findings from an ongoing improvement project to improve antibiotic prescribing for children and adolescents for three acute respiratory tract infections (ARTIs: upper respiratory tract infection, acute bacterial sinusitis, and acute otitis media) among pediatric and family medicine clinics revealed performance gaps between the two primary care specialties. An improvement project was then set up to address the lower performance by family medicine clinics.~Literature review revealed that, in general, quality improvement feedback was more effective if provided to individual clinicians rather than to a group of clinicians, but very limited data existed for antibiotic prescribing practices actually comparing individual clinician feedback to group (clinic-level) feedback.~The hypothesis is that individual clinician data feedback is superior to group (clinic-level) feedback in improving antibiotic prescribing for ARTIs in children and adolescents by family medicine clinicians.~The aim is to determine if there are significant differences for antibiotic prescribing for ARTIs and for broad spectrum antibiotic prescribing percentage between an intervention group and a comparator group of family medicine clinics after the intervention starting November 2015 and ending December 2018.~A cluster randomized trial was designed for 39 family medicine clinics. The intervention group received clinician-level and clinic-level data feedback monthly, and the comparator group received clinic-level only feedback monthly.

Endovascular revascularization and open bypass grafting above the knee show comparable results in primary 2-year patency (about 65%) in medium-length lesions - TASC II, C (Pereira et al, 2006). At the same time, a recent study, where the authors studied the effectiveness of stenting of long lesions (200 mm or more) of the chronic occlusions of the femoropopliteal segments (TASC II, D), showed unsatisfactory results (primary patency 45%) of the stented segment within 2 years (Lin et al, 2015). One of the possible solutions to the problem of breakage of stents in the femoral-popliteal position is a modified method of their manufacture by braiding from nitinol wire. Some studies with interwoven nitinol stents did show their resistance to breakage in this position. Moreover, the primary patency was > 70%. (Werner et al, 2014). These data suggest a better primary patency rate within 2 years with a longer lesion length (>200 mm).~This is a prospective, randomized, open-label study. The main objective of the study is to compare the clinical efficacy and safety of two therapies for the treatment of prolonged atherosclerotic lesions of the arteries of the femoropopliteal segment above the knee, TASC II type D - femoropopliteal proximal shunting and recanalization with angioplasty and stenting using biomimetic interwoven nitinol stent in patients with symptomatic peripheral arterial disease at 24 months. Secondary objectives are to identify predictors of restenosis and occlusions of the operating segment and compare the quality of life of patients after the procedure.~The analysis of literature data showed, that two-year primary patency after endovascular revascularization using a nitinol stent in long lesions was 60%. At the same time, the two-year primary patency after the femoropopliteal proximal bypass was 56% (Enzmann et al. Nitinol stent versus bypass in long femoropopliteal lesions: 2-year results of a randomized controlled trial. JACC: Cardiovascular Interventions. 2019 Dec 23; 12 (24): 2541-9.). Considering these data, it should be assumed that the use of biomimetic interwoven nitinol stents will slightly improve the primary patency parameters within 2 years in the stenting group. The 2-year primary patency after stenting of the femoropopliteal segment with an interwoven nitinol stent was 76% (Scheinert et al., 2011). A power analysis was performed to calculate the sample size of the non-inferiority design for a study power of 80%, a type 1 error probability of 5%, and a non-inferiority margin of 10%. It is planned to recruit 110 patients (55 patients in each group). The observation period of 2 years. Primary endpoint:~-The effectiveness of the method of surgical treatment after 24 months (primary patency, primary-assisted patency, secondary patency).~Secondary endpoints:~Clinical efficacy of the method of surgical treatment after 24 months (MALE);~Safety of the method of surgical treatment in the early postoperative period (hematoma of the surgical access area, peripheral neuropathy, purulent-infectious complications of the surgical access area) and after 24 months (MACE);~Assessment of the quality of life in patients after surgical treatment at 6, 12, and 24 months (SF-36 questionnaire);~Evaluation of prognostic factors for adverse outcomes after surgical treatment. Screening It is performed in patients with a verified diagnosed occlusive lesion of the femoropopliteal segment above the knee joint (type D according to the TASC II classification), with chronic ischemia of the lower extremities of 3-6 categories according to Rutherford.~Assessment of inclusion/exclusion criteria~Assigning a patient number~Study inclusion Collecting baseline information about the patient (history, including information about concomitant therapy, data from the initial physical examination, ultrasound data of the lower limb arteries, CT -arteriography data, assessment of the quality of life using the SF-36 questionnaire. Randomization using the envelope method to one group or another.~Group 1: Femoropopliteal proximal bypass; Group 2: Recanalization of prolonged occlusion of the arteries of the femoral-popliteal segment above the knee joint with angioplasty and stenting with a biomimetic interwoven nitinol stent.~Follow up period; 6, 12, and 24 months.~Performed:~Triplex ultrasound of one lower limb (restenosis, thrombosis, stent breakage);~Leg's roentgenography for the stenting group in two projections, for patients in whom a stent breakage is suspected according to ultrasound;~Consultation with a cardiovascular surgeon.

Endovascular revascularization and open bypass grafting above the knee show comparable results in primary 2-year patency (about 65%) in medium-length lesions - TASC II, C (Pereira et al, 2006). At the same time, a recent study, where the authors studied the effectiveness of stenting of long lesions (200 mm or more) of the chronic occlusions of the femoropopliteal segments (TASC II, D), showed unsatisfactory results (primary patency 45%) of the stented segment within 2 years (Lin et al, 2015). One of the possible solutions to the problem of breakage of stents in the femoral-popliteal position is a modified method of their manufacture by braiding from nitinol wire. Some studies with intervowen nitinol stents did show their resistance to breakage in this position. Moreover, the primary patency was > 70%. (Werner et al, 2014). These data suggest a better primary patency rate within 2 years with a longer lesion length (>200 mm).~This is a prospective, randomized, open-label study. The main objective of the study is to compare the clinical efficacy and safety of two therapies for the treatment of prolonged atherosclerotic lesions of the arteries of the femoropopliteal segment above the knee, TASC II type D - femoropopliteal proximal shunting and recanalization with angioplasty and stenting using biomimetic interwoven nitinol stent in patients with symptomatic peripheral arterial disease at 24 months. Secondary objectives are to identify predictors of restenosis and occlusions of the operating segment and compare the quality of life of patients after the procedure. It is planned to recruit 110 patients (55 patients in each group). Observation period 2 years. Primary endpoint:~-The effectiveness of the method of surgical treatment after 24 months (primary patency, primary-assisted patency, secondary patency).~Secondary endpoints:~Clinical efficacy of the method of surgical treatment after 24 months (MALE);~Safety of the method of surgical treatment in the early postoperative period (hematoma of the surgical access area, peripheral neuropathy, purulent-infectious complications of the surgical access area) and after 24 months (MACE);~Assessment of the quality of life in patients after surgical treatment at 6, 12, and 24 months (SF-36 questionnaire);~Evaluation of prognostic factors for adverse outcomes after surgical treatment.