Cooling Leg and Foot Ulcer Skin Post Healing to Prevent Ulcer Recurrence

Summary: The goal of this study is to test MUSTCOOL, a home-based self-monitoring and self-management ulcer prevention intervention for patients with newly healed chronic venous leg and diabetic foot ulcers. Almost 90% of ulcers recur within 3 months of healing. During the six-month randomized clinic trial, skin temperature will be monitored daily, a maintenance dose of cooling gel pack or placebo will be applied three times weekly to the affected skin, and a bolus dose of cooling will be applied for 5 consecutive days if skin temperature becomes elevated. Outcomes on the incidence of leg ulcer recurrence, pain, physical activity and quality of life will be measured.
Inclusion criteria: inclusion criteria:

 Newly healed leg or diabetic foot ulcer within past 7 - 14 days

 Ankle brachial index 0.8- 1.3mmHg (rule out absence of arterial disease)

 Willing to wear compression stockings and appropriate footwear

 Working freezer

Exclusion criteria: :

 Open leg or foot ulcers

 Cognitive impairment: unable to recall 2 or more words or draw clock Mini-Cog™ for cognitive impairment

 Chronic inflammatory or vascular conditions where blood flow of skin may be impaired such as Lupus erythematosus, Raynaud's, scleroderma, end stage renal disease, chronic regional pain syndrome, multiple sclerosis, hypersensitivity to cold, on chemotherapy

 Unable to preform required protocol activities without assistance (return demonstration to study staff)

['Cooling gel pack', 'Cooling cotton pack']

['Leg Ulcer', 'Venous Hypertension Ulcers', 'Venous Stasis Ulcer', 'Venous Ulcer', 'Venous Insufficiency', 'Foot Ulcer', 'Varicose Ulcer', 'Diabetic Foot']

Leg Ulcer
Venous Hypertension Ulcers
Venous Stasis Ulcer
Venous Ulcer
Venous Insufficiency
Foot Ulcer
Varicose Ulcer
Diabetic Foot


Hypertension Prevention Trial (HPT) Feasibility Study

Summary: To test the feasibility and the efficacy of nutritional interventions in the primary prevention of hypertension in individuals predisposed to the development of hypertension; specifically, to test the hypothesis that reduction of weight and/or decreased sodium intake in obese individuals, or decreased sodium intake with or without increased potassium intake (in men and women, regardless of weight) would prevent the elevation of blood pressure and the incidence of hypertension.
Inclusion criteria: Men and women, ages 25 to 49. Diastolic blood pressure between 78 and 89 mm Hg. Free of major disease. Not on a special diet or antihypertensive medication at entry. Some mild to moderately obese subjects.
Exclusion criteria:

['diet, sodium-restricted', 'diet, reducing', 'potassium']

diet sodium-restricted diet reducing potassium

['Cardiovascular Diseases', 'Heart Diseases', 'Hypertension', 'Obesity', 'Vascular Diseases']

Cardiovascular Diseases
Heart Diseases
Hypertension
Obesity
Vascular Diseases


Phase II Trial of Thalidomide Combined With Concurrent Chemoradiotherapy in Esophageal Cancer

Summary: The purpose of this study is to down-regulate VEGF expression in esophageal cancer patients by thalidomide, so to improve their chemoradiotherapy effect. Patients with esophageal cancer receiving chemoradiotherapy were divided into different sub-group according to dynamic change of their VEGF level,and those showed increased or unchanged VEGF were added thalidomide at random. Efficacy and side effect of thalidomide combined with chemoradiotherapy were evaluated, and at the same time, activity of thalidomide on esophageal cancer and its clinical safely were assessed.
Inclusion criteria: inclusion criteria:

 cytologically or histologically confirmed esophageal carcinoma

 age of 20 -80

 Karnofsky performance status ≥ 70

 no treatments prior to enrollment

 at least one measurable lesion on CT, MRI or esophageal barium exam

 normal functions of heart, lung, liver, kidney and bone marrow

 blood exams qualified for chemotherapy, which included hemoglobulin ≥9 g/dl, neutrophil ≥1.5×109/L and platelet (PLT) ≥100×109/L, creatinine ≤1.5 UNL

 informed consent signed

Exclusion criteria: :

 prior treatments of chemotherapy or irradiation

 poor bone marrow, liver and kidney functions, which would make chemotherapy intolerable

 contraindication for irradiation: complete obstruction of esophagus, deep esophageal ulcer, fistula to mediastinum, or haematemesis

 participating in other clinical trials

 pregnancy, breast feeding, or not adopting birth control

 drug or alcohol addiction, uncontrolled epileptic seizure, or psychotic with no ability of self control

 coexisted morbidities that investigators believed not suitable for chemoradiation

['chemoradiotherapy', 'thalidomide', 'without thalidomide']

chemoradiotherapy
thalidomide
without thalidomide


Study of Yellow Fever Vaccine Administered With Tetravalent Dengue Vaccine in Healthy Toddlers

Summary: The study was designed to evaluate whether the first CYD dengue vaccination can be administered concomitantly with Stamaril® yellow fever vaccine during the same day and visit, but at 2 different sites of administration.~Primary Objective:~To demonstrate the non-inferiority of the immune response against Yellow Fever (YF) in flavivirus (FV) non-immune subjects at baseline receiving one dose of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine compared to participants receiving one dose of Stamaril vaccine concomitantly with placebo.~Secondary Objectives:~To assess the non-inferiority of YF immune response 28 days post-Stamaril vaccination based on seroconversion rates regardless of the FV status of participants at baseline.~To describe the YF immune response 28 days post-Stamaril vaccination in both groups.~To describe the antibody (Ab) response to each dengue virus serotype 28 days post CYD dengue vaccine (Visit [V] 05 and V07), following CYD dengue vaccine Dose 1 and Dose 2 from Group 2 versus following CYD dengue vaccine Dose 2 and Dose 3 for Group 1 (effect of YF vaccination).~To describe the safety of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine, or Stamaril administered concomitantly with placebo.~To describe the safety of CYD dengue vaccine after the first dose of CYD dengue vaccine administered concomitantly with Stamaril vaccine or CYD vaccine administered alone.~To describe the safety of the CYD dengue vaccine in all participants after each dose.
Inclusion criteria: inclusion criteria:

 Aged 12 to 13 months on the day of inclusion.

 Born at full term of pregnancy (>=37 weeks) and with a birth weight >=2.5 kg as reported by the parent/legally acceptable representative.

 Participant in good health, based on medical history and physical examination.

 Participant had completed his/her vaccination schedule according to the official immunization calendar of Colombia and/or Peru, respectively.

 Informed consent form had been signed and dated by the parent(s) or other legally acceptable representative (and by 2 independent witnesses if required by local regulations).

 Participant and parent/legally acceptable representative/tutor able to attend all scheduled visits and to comply with all trial procedures.

Exclusion criteria: :

 Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination.

 Planned participation in another clinical trial during the present trial period.

 Planned receipt of any vaccine in the 4 weeks following first trial vaccination.

 Previous vaccination against YF, hepatitis A, or measles, mumps and rubella.

 Receipt of blood or blood-derived products in the past 3 months which might interfere with assessment of the immune response.

 Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 weeks or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

 Personal known seropositivity for human immunodeficiency virus (HIV) as reported by the parent/legally acceptable representative.

 History of previous maternal vaccination against YF as reported by the parent/legally acceptable representative.

 Personal history of YF or dengue infection/disease as reported by the parent/legally acceptable representative.

 Known systemic hypersensitivity to any of the vaccine components of the vaccines that were used in the trial, or history of a life-threatening reaction to the vaccines used in the trial or to vaccines containing any of the same substances.

 History of contraindication to receipt of vaccines containing components of Stamaril® (yellow fever vaccine), measles, mumps and rubella vaccine, hepatitis A vaccine, pneumococcal conjugated vaccine or of diphtheria (D) toxoid, tetanus (T) toxoid, pertussis toxoid (PT), filamentous hemagglutinin (FHA), polyribosylribitol phosphate (PRP) and polio or other diphtheria, tetanus and pertussis vaccine (e.g., DTwP).

 Thrombocytopenia, as reported by the parent/legally acceptable representative.

 Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular (IM) vaccination.

 History of central nervous system disorder or disease, including seizures.

 Personal history of thymic pathology (e.g., thymoma), and/or thymectomy.

 Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.

 Identified as a child (adopted or natural) of the Investigator or of employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center.

['Live, attenuated dengue serotype 1, 2, 3, and 4 virus', 'Yellow fever vaccine', 'Measles, mumps, and rubella (MMR) vaccine', 'Pneumococcal Conjugated Vaccine', 'Hepatitis A Pediatric Vaccine', 'Diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae vaccine', 'Live, attenuated dengue serotype 1, 2, 3, and 4 virus', 'Yellow Fever Vaccine', 'Placebo (NaCl)', 'Measles, mumps, and rubella vaccine', 'Pneumococcal Conjugated Vaccine', 'Diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae vaccine', 'Hepatitis A Pediatric Vaccine']

Live
attenuated dengue serotype 1
2
3
and 4 virus
Yellow fever vaccine
Measles
mumps
and rubella (MMR) vaccine
Pneumococcal Conjugated Vaccine
Hepatitis A Pediatric Vaccine
Diphtheria
tetanus
pertussis
polio
and Haemophilus influenzae vaccine
Live
attenuated dengue serotype 1
2
3
and 4 virus
Yellow Fever Vaccine
Placebo (NaCl)
Measles
mumps
and rubella vaccine
Pneumococcal Conjugated Vaccine
Diphtheria
tetanus
pertussis
polio
and Haemophilus influenzae vaccine
Hepatitis A Pediatric Vaccine

['Dengue', 'Dengue Hemorrhagic Fever', 'Yellow Fever']

Dengue
Dengue Hemorrhagic Fever
Yellow Fever


Combined Therapy With L-Thyroxine and L-Triiodothyronine Compared to L-Thyroxine Alone

Summary: The objective of this study was to analyze the features of monotherapy with L-T4 in comparison with combined therapy with L-T4 and L-T3 in patients with primary hypothyroidism.
Inclusion criteria: inclusion criteria:

 Premenopausal women with overt primary hypothyroidism (reduced T4 concentration accompanied by increased TSH concentration at the time of initial diagnosis) who did not receive thyroid hormones

Exclusion criteria: :

 Peri- and postmenopause

 Pregnancy

 Major comorbidity

 Use of drugs that affect metabolism or bioavailability of thyroid hormones preparations.

['thyroxine', 'thyroxine and triiodothyronine']

thyroxine
thyroxine and triiodothyronine


The Quality of Life Study in Psoriasis Patients After Ustekinumab Treatment

Summary: This study aims to see if patient quality of life can be approved after treatment with an injectable medication called ustekinumab for the treatment of generalized psoriasis. The investigators hypothesize that the investigators will see improvement in quality of life.
Inclusion criteria: inclusion criteria:

 Subjects are non-immunocompromised males or females 18 years of age or older

 Subjects have moderate-to-severe (≥10% total body surface area) plaque psoriasis

 Subject diagnosed at least 6 months prior to entering the study

 Negative urine pregnancy test within 7 days before the first dose of ustekinumab in all women (except those surgically sterile or at least 5 years postmenopausal)

 Sexually active subjects of childbearing potential must agree to use medically acceptable form of contraception during screening and throughout the study.

 Are considered eligible according to the following tuberculosis (TB) screening criteria:

 Have no history of latent or active TB prior to screening. An exception is made for subjects currently receiving treatment for latent TB with no evidence of active TB, or who have a history of latent TB and documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous antituberculous treatment and provide appropriate documentation.

 Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.

 Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent.

 Within 1 month prior to the first administration of study agent, have a negative QuantiFERON-TB Gold test result, or have a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent. The QuantiFERON-TB Gold test are not required at screening for subjects with a history of latent TB and ongoing treatment for latent TB or documentation of having completed adequate treatment as described above; Subjects with documentation of having completed adequate treatment as described above are not required to initiate additional treatment for latent TB.

 Have a chest radiograph both posterior-anterior and lateral views, taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB.

 Subject meets concomitant medication requirements or agrees to complete a washout for restricted medications prior to starting the study.

 Washout Period :

 Must not have initiated or changed any other medications that could affect psoriasis (e.g. beta blockers, lithium salts, antimalarials) within the 4 week period prior to Week 0 or during the study

 Subjects must not have received immunosuppressive, chemotherapy and/or systemic therapy including oral calcineurin inhibitors (such as cyclosporine), retinoids (Vitamin A and analogues), Methotrexate, Azathioprine, 6-thioguanine, Mycophenolate mofetil (MMF), Hydroxyurea, or cytokines (such as interferon-gamma) within the 4 week period prior to Week 0 or during the study

 Subjects must not have received phototherapy (broadband or narrow-band UVB) within the 2 week period prior to Week 0 or during the study.

 Subjects must not have received photochemotherapy (PUVA) within the 4 week period prior to week 0 or during the study

 Subjects must not have received TNF-α inhibitors (such as infliximab, etanercept, adalimumab) within the 12 week period prior to Week 0 or during the study

 Subjects must not have received alefacept within the 12 week period prior to Week 0 or during the study.

 Subjects must not have received ustekinumab within the 12 week period prior to Week 0 or during the study.

 Subjects must not have received treatment with an investigational drug within the previous 4 weeks or 5 half-lives prior to Week 0 (whichever is longer) or participation in another clinical trial within the 4 week period prior to Week 0 or during the study

Exclusion criteria: :

 Subject is younger than 18 years of age.

 Subject has less than 10% body surface involvement of his/her psoriasis.

 Subjects with erythrodermic, pustular, or guttate psoriasis

 History of known or suspected intolerance to any of the ingredients of the investigational study product.

 Evidence of skin conditions other than psoriasis that would interfere with study-related evaluations of psoriasis.

 Evidence of active infections such as fevers, chills, sweats, or history of untreated Lyme disease and active severe infections within 4 weeks before screening visit, or between the screening and Week 0 visits

 Subject has a history of listeriosis, untreated TB, persistent or active infections requiring hospitalization or treatment with IV antibiotics, IV antiretrovirals, or IV antifungals within 30 days of baseline, or oral antibiotics, antivirals, or antifungals for purpose of treating infection, within 14 days of baseline.

 Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening.

 Refer to inclusion criteria for information regarding eligibility with a history of latent TB.

 Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.

 Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of malignancy or current active infection, including TB.

 Have had a nontuberculous mycobacterial infection or opportunistic infection (eg. Cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.

 History of immune compromised status [e.g. human immunodeficiency virus (HIV) positive status or other immune suppressing drug] or a congenital or acquired immunodeficiency or subject testing positive for HIV, Hepatitis B, and/or Hepatitis C during screening procedures.

 Subject has a poorly controlled medical condition including, but not limited to, unstable cardiovascular disease, poorly controlled diabetes, recent stroke, history of recurrent infections, or any other condition for which, in the opinion of the investigator, participation in the study would place the subject at risk

 Subject has a history of or ongoing drug or alcohol abuse

 Subject is not willing to comply with wash-out requirements (see above)

 Subject is known, or suspected of being unable to comply with the study protocol


Evaluation of the Safety and the Ability of a DNA Vaccine to Protect Against Dengue Disease

Summary: The purpose of this study is to determine whether a new investigational dengue vaccine is safe, well-tolerated, and to see if an immune response against dengue disease will be generated.
Inclusion criteria: inclusion criteria:

 Male or female age 18 to 50 (inclusive) years old at the time of enrollment

 Have negative anti-dengue, Japanese encephalitis, West Nile, and yellow fever ELISA serological tests

 Be informed of the nature of the study and provide written informed consent

 If the subject is of child-producing potential, he/she agrees to practice adequate birth control or abstain from sex

 Have access to the WRAIR Clinical Trials for at least 270 days, and be willing to refrain from participation in other investigational clinical trials

 Be in good general health

Exclusion criteria: -Subjects meeting any of the following criteria will be excluded from the study:

 History of Flavivirus infection or history of Flavivirus vaccine (experimental or licensed product) including Japanese encephalitis, yellow fever, and dengue

 Have a known or suspected hypersensitivity or adverse reaction to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain

 Have received a live-attenuated vaccine within 42 days prior to the initial injection on Day 0 or a subunit or killed vaccine within 30 days of the initial injection on Day 0

 Have a positive screen for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or HIV antibody

 Are pregnant or breastfeeding

 Have donated or received blood, blood products, or plasma within 30 days prior to Day 0

 Have any acute illness, including an oral body temperature >100.4°F, within 7 days before the initial injection on Day 0

 Have a past or current history of malignant disease except for adequately treated skin cancer

 Exclusions include but are not limited to conditions pertaining to or evidence of immunodeficiency; allergies requiring treatment with antigen injections; autoimmune disease; severe migraine headaches; unstable asthma; clinically significant cardiac arrhythmias, diabetes mellitus, thyroid disease, a bleeding disorder or a seizure disorder.

 Have participated in an investigational drug, vaccine, or device study within a period of 30 days prior to Day 0;

 History of splenectomy

 Planned travel to dengue endemic areas during the study period

['Tetravalent Dengue Vaccine (TVDV)', 'Tetravalent Dengue Vaccine (TVDV) with Vaxfectin® (low-dose)', 'Tetravalent Dengue Vaccine TVDV with Vaxfectin® (High Dose)']


Satiety Innovation- Study 793. University of Aberdeen

Summary: The proposed study will address the effect of developed novel food products through processing innovation on motivation to eat, biomarkers of satiety, nutrient bioavailability and gut health using in vivo studies and validating new in vivo approaches.~Specifically in this protocol we will address, in a short human intervention study the effect of a potentially satiating product on appetite, appetite biomarkers, particularly the influence on gut microbiota, tolerance and safety of the products in healthy obese and overweight volunteers in free living conditions.
Inclusion criteria: inclusion criteria:

 Males and females

 18-65 years old

 Body Mass Index (BMI) 27-35kg/m2

 Overall healthy

 Weight Stable (<3 kg change in the past 4 months, before the trial).

Exclusion criteria: :

 Medical:

 Heavy smokers (more than 10 cigarettes/day) or heavy alcohol consumers (more than 4 alcohol units/day for male and more than 3 alcohol units/day for female).

 Obesity of endocrine origin.

 Chronic metabolic conditions: diabetes, hepatic disease, gout, kidney, thyroid or coagulation disease.

 Gastrointestinal disorders: celiac disease, ulcerative colitis, irritable bowel syndrome (IBS), Chron's disease, chronic constipation, diverticulitis, history of gastric bezoar. Suspected strictures, fistulas, or physiological GI obstruction.

 Psychiatric disorder: severe depression, bulimia, anorexia, schizophrenia, bipolar disorder.

 Gastrointestinal procedure or surgery in the past three months.

 Disorders of swallowing, severe dysphagia to food or pills.

 Pregnancy

 Medication


Persistence of Bactericidal Antibodies in Adults Who Received a Booster Dose of Menactra® Approximately 4 Years Earlier

Summary: The aim of this study is to provide information on the persistence of bactericidal antibodies following Menactra booster vaccination in study MTA77 ( NCT01442675).~Objective:~To evaluate the persistence of antibody responses (determined by a serum bactericidal assay using human complement (SBA-HC)) approximately 4 years after the administration of a booster dose of Menactra vaccine in trial MTA77
Inclusion criteria: inclusion criteria:

 Aged ≥ 18 years on the day of inclusion

 Received booster dose of Menactra vaccine in trial MTA77

 Informed consent form has been signed and dated

 Able to attend the scheduled visit and to comply with all trial procedures.

Exclusion criteria: :

 Participation at the time of trial enrollment (or in the 4 weeks preceding trial enrollment) in another clinical trial investigating a vaccine, drug, medical device, or medical procedure

 Receipt of any meningococcal vaccine, including serogroup B meningococcal vaccine, after receipt of the booster dose of Menactra vaccine administered in trial MTA77

 Receipt of immune globulins, blood or blood-derived products in the past 3 months

 Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

 History of meningococcal infection, confirmed either clinically, serologically, or microbiologically

 Bleeding disorder, thrombocytopenia, or receipt of anticoagulants contraindicating venipuncture at the discretion of the Investigator

 Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily

 Current alcohol abuse or drug addiction

 Any illness that, in the opinion of the Investigator, might interfere with trial conduct or trial results

 Receipt of oral or injectable antibiotic therapy within 72 hours prior to the blood draw. (A prospective subject should not be included in the trial until 72 hours has passed.)

 Identified as an Investigator or employee of the Investigator or trial center with direct involvement in the proposed trial, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed trial.

['Meningococcal (Groups A, C, Y, and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine']

['Meningitis', 'Meningococcal Meningitis', 'Meningococcal Infections']

Meningitis
Meningococcal Meningitis
Meningococcal Infections


Macrolide Maintenance Therapy in Chronic Obstructive Pulmonary Disease

Summary: To assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the preceding year of inclusion can decrease the exacerbation rate in the year of treatment.
Inclusion criteria: inclusion criteria:

 Diagnosis of COPD according to GOLD criteria (FEV1/FVC<70%), classification into GOLD I (FEV1 70-100% predicted), GOLD II (FEV1 50-70% predicted), GOLD III (FEV1 30- 50% predicted) or GOLD IV (FEV1 ≤ 30% predicted)

 Age ≥ 18 years

 Three or more exacerbations of COPD in one year for which a course of prednisone and/or antibiotic therapy was started

 Clinically stable during 1 month. Patients have to be free of COPD exacerbation or respiratory tract infection within a month prior to involvement in the study and they should not have received a high dose of systemic glucocorticoids or antibiotics in this period

 Informed consent

Exclusion criteria: :

 Use of antibiotics or high dose of systemic steroids within a month prior to involvement in the study.

 Addition of inhalation steroids to the patient's therapy regimen, shortly before entering the study.

 Pregnant or lactating women.

 Allergy to macrolides.

 Liver disease (alanine transaminase and/or aspartate transaminase levels 2 or more times the upper limit of normal).

 Asthma, defined as episodic symptoms of airflow obstruction which is reversible with bronchodilators, assessed with lung function testing.

 Presence of a malignancy which is clinically active.

 Bronchiectasis.

 Malignancy of any kind for which the subject is under treatment or is being monitored as part of follow up after treatment.

 Heart failure.

 Use of drugs which can adversely interact with macrolides and for which therapeutic monitoring cannot be undertaken.


Angiotensin Converting Enzyme Inhibitors During Cardiopulmonary Bypass in Infants and Children

Summary: The purpose of this study is to determine whether ACE inhibitors alter the fibrinolytic, inflammatory, and hemodynamic response to cardiopulmonary bypass in infants and children with congenital heart disease.
Inclusion criteria: inclusion criteria:

 Infants or children (newborn to 17 years of age) undergoing cardiopulmonary bypass for elective surgical correction of a congenital heart defect.

 Patients must be taking an ACE inhibitor prior to their operation

Exclusion criteria: :

 Patients in which discontinuing ACEIs is deemed unsafe by their primary cardiologist

 Any condition rendering the subjects legal guardian unable to understand the nature, scope, and possible consequences of the study.

 Pregnancy as ruled out by standard of care screening procedures.

 Individuals whose weight is less than 3.5 kg at the time of enrollment.

 Inability to comply with the protocol. ie. Children in whom it is deemed unsafe to have the extra blood draws, and children who are thought to be noncompliant with their medications.

['Angiotensin Converting Enzyme Inhibitor', 'No ACE Inhibitor']

Angiotensin Converting Enzyme Inhibitor
No ACE Inhibitor


Oral Human Papillomavirus Infection in HIV-infected Men

Summary: Human papillomavirus (HPV)-infection belong to the most common sexually transmitted diseases worldwide. HIV-infected men having sex with men /MSM) are strongly associated with a higher prevalence of genitoanal HPV-infection, and perianal HPV-infections have been detected in up to 90% of HIV-positive men. The data concerning the incidence of oral HPV-infection in HIV-positive men, especially in the era of highly antiretroviral therapy, are conflicting. Thus, this prospective study mainly focuses on the incidence and prevalence of oral HPV-infection, spectrum of HPV-types, and oral high-risk HPV viral load in HIV-positive men.
Inclusion criteria: inclusion criteria:

 HIV-infected men who have sex with men

Exclusion criteria: :

 None

['Oral swabs for HPV-typing and high-risk HPV-determination']

['Papillomavirus Infections', 'HIV Infections']

Papillomavirus Infections
HIV Infections


Optimal Management of Malignant Dysphagia

Summary: According to the Canadian Cancer Society there are approximately 1700 new cases of esophageal cancer per year in Canada. As most of these patients are diagnosed in advanced stages of the disease, 1800 deaths are estimated from this cancer annually . Progressive dysphagia is the most common presenting symptom and impacts not only the patient's quality of life but the ability to tolerate life prolonging treatments such as systemic chemotherapy.~Although there are several therapeutic modalities to alleviate malignant dysphagia including laser, photodynamic therapy and cryotherapy , the use of stents and radiotherapy are the most commonly employed. However, the optimal approach to effective, timely treatment of malignant dysphagia remains a challenge. The investigators conducted a preliminary retrospective review to investigate such palliation procedures and found that a multi-modality approach may yield the most favourable results .~Therefore, our clinical trial will examine the effectiveness of adding a single dose of brachytherapy to patients with severe dysphagia who have already been treated with a endoscopically placed self-expanding metallic stent.
Inclusion criteria: inclusion criteria:

 Age ≥18 years

 Confirmed esophageal/gastroesophageal (GEJ) cancer (Siewert Type I and Type II only) of any histology on biopsy

 Dysphagia score ≥2

 Stage IV cancer/Metastatic disease

Exclusion criteria: :

 Expected life expectancy < 3 months

 Inability to undergo stent insertion

 Siewert Type III gastroesophageal cancer

 Esophageal-Airway fistula

['Malignant Dysphagia', 'Esophageal Cancer']


Preventing Acute Chest Syndrome by Transfusion Feasibility Study

Summary: Acute chest syndrome (ACS) is similar to severe pneumonia and is a common cause of hospitalizations for people with sickle cell disease (SCD). Blood transfusions are one treatment option for ACS. High levels of an enzyme called secretory phospholipase A2 (sPLA2) may be present in people before they develop ACS. This study will determine how well sPLA2 levels can predict the onset of ACS and whether identifying high sPLA2 levels allows enough time to prevent ACS with blood transfusions. Results from this study will help to determine the feasibility of conducting a larger study that would further examine the use of sPLA2 levels and blood transfusions to prevent ACS in people with SCD.
Inclusion criteria: inclusion criteria for the Observational and Trial Cohorts:

 Hemoglobin diagnosis of SS (two copies of the hemoglobin S gene), SC (one copy of the hemoglobin S gene and one copy of the hemoglobin C gene), or S-β thalassemia (β+ or β0)

 No clinically apparent ACS

 No prior participation in either part of the study

 inclusion criteria for the Trial Cohort, in addition to the above criteria:

 sPLA2 level greater than 100 ng/mL within the same 24-hour window that coincides with fever and chest radiograph negative for new pulmonary infiltrate within the last 12 hours of the 24-hour window

 Fever greater than 38.0º C within the same 24-hour window that coincides with elevated sPLA2 level (greater than 100 ng/mL) and chest radiograph negative for new pulmonary infiltrate within the last 12 hours of the 24-hour window

 Chest radiograph negative for new pulmonary infiltrate within the last 12 hours of the 24-hour window of an abnormal sPLA2 level and fever

 Hemoglobin levels equal or less than 10 g/dL at time of study entry

 Informed consent of parent(s) or legal guardian; informed consent or assent of participant as applicable

Exclusion criteria:  for Observational and Trial Cohorts:

 Existing diagnosis of a new pulmonary infiltrate diagnosed by chest radiography (pleural effusion not obscuring lung parenchyma will not exclude the person from the study)

 Any coexisting medical condition for which the physician feels that a transfusion may be needed within 24 hours (e.g., severe anemia, stroke)

 Red Blood Cell (RBC) transfusion in the 60 days before study entry

 Unwillingness to sign consent form, or if a minor, unwillingness of parent/guardian to sign consent form

 Treatment with any investigational drug or device in the 30 days before study entry (hydroxyurea is allowable)

 History of alloimmunization that would prevent the participant from receiving blood within 8 hours of eligibility for study entry or history of a life-threatening transfusion reaction

 Objection to transfusion for religious or other reasons from either the participant or guardian

 History of treatment with systemic steroids within 1 week of study entry (inhaled steroids are acceptable)

 Pregnant

['Single blood transfusion', 'Standard care']


Q-collar and Brain Injury Biomarkers

Summary: Significant morbidity, mortality, and related costs are caused by traumatic brain injury (TBI). A simple, effective, and lightweight device worn by athletes or war fighters in the field, designed to mitigate TBI resulting from blast trauma or concussive events, would save lives, and the huge costs currently being experienced for life-treatment of surviving victims. An externally-worn medical device that applies mild jugular compression according to the principle of the Queckenstedt Maneuver (the Device) is being developed by Q30 Labs, LLC (Q30). Initial research suggests that the Device has the potential to reduce the likelihood of TBI. The currently developed collar (Smith 2009; Smith 2011; Smith 2011; Smith 2012) has been approved for studies in humans and the results indicate safety for use during high demand and maximal exertion activities, Study ID: 2013-2240, Institutional Review Board - Federalwide Assurance #00002988). Regarding safety, the externally worn collar is meticulously designed to mimic the body's own omohyoid muscle actions upon the jugular veins that will provide similar pressure and volume increases not to surpass that of a yawn or the mere act of just lying down.~This study will investigate the effectiveness of this device in high school athletes playing a collision or contact sport such as football, hockey, or lacrosse. The high risk sports which utilize helmets during competition will allow for measurements systems to be embedded in the headgear and will not affect play or fit of equipment. Athletes participating in this study will be enrolled into one of two groups 1) device wearing or 2) non-device wearing. By the nature of the sports selected, it is likely this pilot study will primarily include males, however if any female meets inclusion criteria on the team selected they will be included in this pilot investigation. The helmets of all participants will be outfitted with an accelerometer which will measure the magnitude of every impact to the head sustained by the athlete. Effectiveness of the device will be determined by brain imaging during the pre-season, midseason, and end of season time points. A subset of athletes who report a diagnosed concussion will also receive additional brain imaging within the week following the diagnosed concussive event.
Inclusion criteria: inclusion criteria:

 • Normal healthy volunteer

 Able to provide written consent

 Must be 14 years or older and a participant on a competitive and organized sports program

 Neck circumference of 15 ½ - 16 ½ inches

Exclusion criteria: :

 • Unable to provide written consent

 History of neurological deficits, previous cerebral infarction, or severe head trauma

 Medical contraindications to restriction of venous outflow via the internal jugular veins (known increased intracerebral pressure, metabolic acidosis or alkalosis)

 Glaucoma (Narrow Angle or Normal Tension)

 Hydrocephalus

 Recent penetrating brain trauma (within 6 months)

 Known carotid hypersensitivity

 Known increased intracranial pressure

 Central vein thrombosis

 Any known airway obstruction

 Any known seizure disorder


Ph I Study of Lithium During Whole Brain Radiotherapy For Patients With Brain Metastases

Summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as lithium, may protect normal cells from the side effects of radiation therapy. Giving lithium together with radiation therapy may allow a higher dose of radiation therapy to be given so that more tumor cells are killed.~PURPOSE: This phase I trial is studying the side effects and best dose of lithium when given together with whole-brain radiation therapy in treating patients with brain metastases from primary cancer outside the brain.
Inclusion criteria: inclusion criteria:

 Histopathologically confirmed extracranial primary malignancy

 Multiple (i.e., > 3) brain metastases OR < 3 metastases with at least 1 metastasis > 4.0 cm in diameter

 Not eligible for radiosurgery

 No requirement for immediate whole-brain radiotherapy

 No metastases to the midbrain or brainstem

Exclusion criteria: :

 Zubrod performance status 0-2

 Life expectancy ≥ 8 weeks

 Platelet count > 100,000/mm^3

 ANC > 1,500/mm^3

 Hemoglobin ≥ 10 g/dL

 BUN < 25 mg/dL

 Creatinine < 1.5 mg/dL

 Bilirubin < 1.5 mg/dL

 ALT ≤ 2 times normal

 Sodium > 136 mg/dL

 Not pregnant or nursing

 Negative pregnancy test

 Fertile patients must use effective contraception

 Neurologically stable

 No seizure disorders or seizures due to brain metastases

 No medical illnesses or psychiatric conditions that would preclude completion of study treatment

 No sensory neuropathy ≥ grade 2

 No bipolar disorder

 No thyroid disease

 No QTc interval prolongation

 PRIOR CONCURRENT THERAPY:

 More than 2 weeks since prior and no concurrent chemotherapy

 At least 2 weeks since prior and no concurrent NSAIDs, angiotensin-converting enzyme inhibitors (e.g., enalapril or captopril), calcium channel blockers, diuretics, selective cyclooxygenase-2 inhibitors, acetazolamide, urea, xanthine, or alkalinizing agents (e.g., sodium bicarbonate)

 No prior radiotherapy to the head and neck area

 No prior radiosurgery

 No concurrent radiotherapy to other sites

 No concurrent anticonvulsants due to brain metastases

 No concurrent psychoactive drugs

 No concurrent thyroid medications

 No concurrent amifostine

['lithium carbonate', 'cognitive assessment', 'quality-of-life assessment', 'radiation therapy']

lithium carbonate
cognitive assessment
quality-of-life assessment
radiation therapy

['Brain and Central Nervous System Tumors', 'Cognitive/Functional Effects', 'Neurotoxicity', 'Solid Tumor']

Brain and Central Nervous System Tumors
Cognitive/Functional Effects
Neurotoxicity
Solid Tumor


Inter-Observer Reliability and Accuracy of Tricuspid Annular Plane Systolic Excursion in Patients With Suspected PE in the ED

Summary: The purpose of this study will be to evaluate the measurement of tricuspid annular plane systolic excursion (TAPSE) by emergency physician performed echocardiogram on patients with suspected pulmonary embolism (PE) who are scheduled to get a computed tomography of the pulmonary arteries (CTPA)
Inclusion criteria: inclusion criteria:

 Concern for PE by attending physician and CTPA ordered

Exclusion criteria: :

 If patient is under the age of 18, a prisoner, or a ward of the state

 CTPA ordered but not performed


Trial of the MEND Childhood Obesity Treatment Program

Summary: The number of children who are obese in the UK is steadily increasing with both short and long term consequences for health. The aim of this study is to determine whether the MEND Programme (a new national initiative for the treatment of childhood obesity) is a successful and sustainable treatment for childhood obesity and obesity related health problems.~300 overweight and obese children will be randomly assigned to start immediately on the MEND Programme for 6 months or join a waiting-list control group for 6 months. Measurements of health outcomes will be taken at baseline, and at 6, 12 and 24 months after the Programme. After 6 months of waiting-list time, the control group will follow the same protocol as the immediate starters. The researchers will be unaware (blinded) to which group each child has been assigned to. The study will examine the effects of the MEND Programme on body composition, cardiovascular health and psychological health.
Inclusion criteria: inclusion criteria:

 Children enrolled in the MEND Programme who are yet to be given a start date for the programme.

 Aged between 7-13 years old.

 Overweight or obese as defined by a BMI which falls above the 91st centile on the boys/girls BMI chart UK cross-sectional reference data:1997/1).

 Clinically well with no known chronic illness.

Exclusion criteria: :

 Age less than 7 years or older than 13.

 Known chronic illness.

['MEND Childhood Obesity Program', 'Control Group']

MEND Childhood Obesity Program
Control Group


Reperfusion of Pulmonary Arteriovenous Malformations After Embolotherapy

Summary: AVMs are abnormal collections of blood vessels which can occur in any part of the body including the lungs. These blood vessels are weakened and can rupture anytime causing bleeding which can be massive, leading to life-threatening conditions.~Pulmonary AVMs occur in about 40% of patients with HHT. Each patient may have an average of 5 AVMs .Rupture of the AVM can lead to massive bleeding in the lung, stroke and infection of the brain. In order to prevent these complications, patients with HHT are routinely examined for pulmonary AVMs and treatment with embolization is recommended.~AVMs have a main blood vessel or artery supplying blood to the collection of blood vessels. The way to treat AVMs is cut off their blood supply through a process called embolization.~Embolization is a standard medical procedure which is done to stop or prevent hemorrhage (bleeding) from an AVM. It involves blocking the artery that supplies blood to the AVM by inserting a foreign body, into the blood vessel supplying blood to the AVM.~Standard devices used for embolization include coils (made of stainless steel or platinum). These devices usually have a good success rate for blocking the artery that supplies blood to the AVM. However, a few AVMs that are embolized by standard devices may reopen over time. This is called reperfusion and will require repeat embolization procedures.~For embolization of pulmonary AVMs at St. Michael's Hospital, the Nester coil is used. In this study, we would like to compare the Nester coil with a new coil device called the Interlock Fibered IDC Occlusion System. Both coils are approved for use in Canada, however the cost of the IDC coil limits its use at this hospital.~Compared to the Nester coil, the IDC coils are made so that they can be removed or repositioned if they are not placed correctly. The coil also allows tighter packing which helps prevent reperfusion.~This study will compare the success rate of embolization between the Interlock™ Fibered IDC™ Occlusion System (IDC coil) and the Nester coil.
Inclusion criteria: inclusion criteria:

 Patients are eligible for inclusion in the study if all the following criteria are met:

 Documented presence of new (untreated) pulmonary AVMs requiring embolization

 Definite clinical diagnosis of HHT or genetic diagnosis of HHT

 Age ≥18 years

 Able to provide informed consent

Exclusion criteria: :

 Patients will be excluded from the study if, in the opinion or knowledge of the Principal Investigator any of the following criterion is present:

 Participants with multiple AVMs within close proximity where identification of the aneurysm seen on CT cannot be precisely isolated for randomization purposes.

 Contra-indications to embolotherapy

 Severe chronic renal failure, without availability of dialysis

 Severe pulmonary hypertension (PA systolic estimated at >60mmHg)


Dietary Fiber for Fecal Incontinence

Summary: The primary aim of this study was to compare the effects of supplementation with one of three dietary fibers (gum arabic, carboxy-methylcellulose, or psyllium) or a placebo on fecal incontinence (FI), symptom intolerance, and quality of life in community-living individuals who have incontinence of loose or liquid feces. A secondary aim was to explore the possible mechanism(s) underlying the supplements' efficacy (i.e., improvements in stool consistency, water-holding capacity or gel formation).
Inclusion criteria: inclusion criteria:

 age ≥18 years

 living in the community (not a nursing home or assisted living facility)

 self-report of usually having FI of loose or liquid consistency at least twice in a 2-wk period

 toilets independently

 ability to read and write in English.

 Persons that regularly performed pelvic floor muscle exercises and/or biofeedback on a maintenance regimen for at least 20 wks or who took a steady dose of anti-motility medications on a regular schedule that still met the FI criteria were also eligible.

Exclusion criteria: :

 difficulty swallowing,

 a gastrointestinal (GI) tract altered by surgery,

 a malabsorption disorder,

 inflammatory bowel disease,

 gastrointestinal cancer or active cancer treatment,

 allergy to the fibers,

 regularly used a laxative or enema, were tube-fed, or unwilling to discontinue taking periodic self-prescribed fiber supplements or anti-diarrheal medications.

 a score ≤24 on the Mini Mental State Examination

 having/reporting fewer than two episodes of FI or being incapable of performing study procedures during the run-in baseline period

['Psyllium', 'Gum Arabic', 'carboxymethylcellulose', 'Placebo']

Psyllium
Gum Arabic
carboxymethylcellulose
Placebo


18F-FSPG PET/CT in Imaging Patients With Newly Diagnosed Lung Cancer or Indeterminate Pulmonary Nodules

Summary: This clinical trial compares fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) positron emission tomography (PET)/computed tomography (CT) to the standard of care fluorodeoxyglucose F-18 (18F-FDG) PET/CT in imaging patients with newly diagnosed lung cancer or indeterminate pulmonary nodules. PET/CT uses a radioactive glutamate (one of the common building blocks of protein) called 18F-FSPG which may be able to recognize differences between tumor and healthy tissue. Since tumor cells are growing, they need to make protein, and other building blocks, for cell growth that are made from glutamate and other molecules. PET/CT using a radioactive glutamate may be a more effective method of diagnosing lung cancer than the standard PET/CT using a radioactive glucose (sugar), such as 18F-FDG.
Inclusion criteria: inclusion criteria:

 - Have an indeterminate untreated pulmonary nodule (IPN) (7-30 mm diameter) on CT, or an indeterminate lung mass (> 30 mm diameter), without prior examinations that establish that the lesion has been stable for two or more years, untreated.

 or

 Have a newly diagnosed, untreated primary lung cancer diameter 7 mm or more.

 Be able to give informed consent, which will include a layman's explanation of the estimated amount of additional radiation that the patient will receive from the investigational PET/CT scan using 18F-FSPG

 Must agree at the time of study entry to undergo clinically indicated biopsy(ies) or a 24-month period of follow-up, as needed, to resolve the etiology of their IPN(s) or lung mass(es).

Exclusion criteria: :

 Pregnant or lactating patients will be excluded, as will females of childbearing potential who refuse to undergo a serum or urinary beta-HCG pregnancy test the day of either the 18F-FSPG or the 18F-FDG PET/CT scans, in accordance with the standard policy of the Medical Imaging Service at our facility. Women who have experienced 24 consecutive months of amenorrhea, have reached at least 60 years of age, or have had a tubal ligation or hysterectomy documented in their medical records are considered not to be of childbearing potential for the purposes of this protocol

 Patients with a body weight of 400 pounds or more or a body habitus or disability that will not permit the imaging protocol to be performed

 A recognized active lung infection

 Previous systemic or radiation treatment for cancer of any type within 1 year

 For patients who do not have a tissue diagnosis:

 Non-oncologic severe co-morbidities suggesting a life span of less than two years if not treated, as determined by the potential subject's treating physician.

['Computed Tomography', 'Computed Tomography', 'fluorodeoxyglucose F-18', 'Fluorine F 18 L-glutamate Derivative BAY94-9392', 'Laboratory Biomarker Analysis', 'Positron Emission Tomography', 'Positron Emission Tomography (PET)']

['Lung Carcinoma', 'Solitary Pulmonary Nodule', 'Cigarette Smoking Behavior']

Lung Carcinoma
Solitary Pulmonary Nodule
Cigarette Smoking Behavior


Effects of Brain Stimulation on Food Intake and Behavioral Weight Loss Treatment

Summary: This study will determine whether electrical stimulation of an area of the brain called the dorsolateral prefrontal cortex, which is important in determining the feeling of fullness after eating, affects how much food a person eats and weight loss over 4 weeks. It will also compare weight changes in people who attend weight loss counseling sessions and those who do not over this period of time.~Obese, non-diabetic people between 18 and 60 years of age who are in good health and who live in the Phoenix, AZ, metropolitan area are eligible for this study. Candidates must have a body mass index of 35 kg/m(2) or more and weigh less than 350 pounds.~Participants are admitted to the NIH inpatient unit in Phoenix for the first 9 days of the study for tests, which include meal tests to determine eating behaviors and caloric intake, blood and urine tests, glucose tolerance test, weight measurement, psychological assessments and DEXA scan to measure body fat. For 3 of the days, they will be asked to eat all of their food from automated vending machines. Some subjects receive transcranial direct current stimulation (TDCS). For this procedure, electrodes that conduct electricity are placed on the head and arm and the current is turned on for 40 minutes. Some tingling may be felt under the electrodes. Other subjects receive sham TDCS, with the current turned on only very briefly.~After the evaluations, subjects are discharged home from the NIH unit and instructed to eat 25 percent fewer calories than they consumed while on a weight maintenance diet the first 3 days of their inpatient stay. They maintain the lower calorie diet at home for 4 weeks. During this period they come to the NIH unit 3 days a week to receive either real or sham TDCS.
Inclusion criteria: inclusion criteria:

 BMI greater than or equal to 25 kg/m(2).

 Age 18-60 years. Women who are post-menopausal will be excluded from the study due to changes in their metabolism that could affect weight loss. We will set the cutoff at age 60 so that the age difference between the men and women is not too great for analysis purposes. Minors under the age of 18 will be excluded because the time requirements of the study are such that they would interfere with school schedules.

 Right-handedness (because the treatment will be given to the left dorsolateral prefrontal cortex and the evidence accumulated in this region was only in right-handed individuals)

 Weight stable (plus or minus 5 percent) for last 3 months as determined by volunteer report.

Exclusion criteria: :

 Weight > 300 lbs (136 kg), as this is the weight limit of the fMRI machine

 Use of medication affecting metabolism and appetite in the last three months

 Current pregnancy, pregnancy within the past 6 months or currently lactating

 History or clinical manifestations of acute or chronic disorders or conditions that may affect appetite or energy expenditure (such as, but not limited to type 1 or type 2 diabetes, Cushing s disease, thyroid disorders, coccidiomycoses)

 Gastrointestinal disease, including inflammatory bowel diseases (e.g. Chron s disease and ulcerative colitis), malabsorption syndromes (e.g. celiac disease), gastric ulcer (active) which may alter metabolism

 Current, unstable medical conditions such as hepatitis, renal insufficiency, cancer requiring treatment in the last 5 years, or central nervous system disorders etc. as assessed by history and physical exam

 Evidence of alcohol abuse as defined by greater than or equal to 8 point score on the Alcohol consumption screening AUDIT questionnaire in adults

 Evidence of nicotine use or of drug use such as amphetamines, cocaine, heroin, or marijuana

 Postmenopausal women or symptoms of perimenopause (e.g. hot flashes, onset of irregular periods following age 40, elevation of FSH >20 IU following age 40 years)

 Any conditions contraindicated for MRI (e.g., pacemaker, metal in the cranial cavity, significant claustrophobia, holes in the skull made by trauma or surgery)

 Any condition not specifically mentioned above that, in the opinion of the investigator, may interfere with the study or prove unsafe for participation.

['Transcranial Direct Current Stimulation (TDCS)', 'Sham/no-stimulation']

['Electric Stimulation Therapy', 'Obesity', 'Weight Loss', 'Eating']

Electric Stimulation Therapy
Obesity
Weight Loss
Eating


Study of the Efficacy of Sharp Debridement for the Management of Chronic Wounds

Summary: Standard care of care and up to twelve (12) weekly debridements. Subjects randomized into the weekly debridement group will receive up to twelve (12) debridement during the twelve (12) weeks of the study. There will be two (2) subject groups in the study. Subjects will be randomized into either the monthly debridement group or the weekly debridement group.
Inclusion criteria: inclusion criteria:

 Subject must have evidence of a full-thickness cutaneous wound of at least 30 days duration.

 Subject must be at least 18 years of age.

 Subject must have a minimum life expectancy of at least 1 year to be determined by the Investigator.

 The study ulcer must be from 1 cm2 to 20 cm2 in size.

 The study ulcer must have been present for at least 30 days at study Day -7.

 The subject's Glycosylated hemoglobin (HbA1C) must be equal to or less than 10.0% for subjects with diagnosed diabetes at study Day 0.

 The subject, legal guardian or authorized representative must have understood, signed and dated the IRB approved informed consent form.

 The subject must be available for evaluation on a weekly basis for the twelve (12) weeks of the study. Visits at Week 13 and Week 14 are required for initial wound healing, which is achieved in study Week 11 or 12. The Investigator will evaluate both groups at Week 16. Subjects must be available for evaluation at Week 16.

 The subject's TCpO2 must be equal to or greater than 25 mm of mercury in the periwound area and ABI greater than 0.7.

Exclusion criteria: :

 Subject whose ulcer has healed 30% or greater from the evaluation Study day -7 to the post-debridement Study Day 0 as determined by wound measurements using ARANZ Silhouette

 A history of alcohol or substance abuse, within the previous year, which could, or in the judgment of the Investigator, would interfere with study compliance or protocol requirements.

 Participation in clinical trials evaluating investigational pharmaceuticals, biologics or devices within 30 days of admission to the study.

 Subject with a history of receiving any of the following within the last 30 days: systemic corticosteroids exceeding a total daily dose of 20mg, immunosuppressive agents, radiation therapy or chemotherapy. Anticipated use of the above during the study period will also exclude a subject from entry into the study. Topical and inhaled corticosteroids are not prohibited.

 Subjects with medical comorbidities known to affect wound healing such as end stage renal disease, severe hepatic insufficiency, vasculitis, and HIV will be excluded from this study


Nebulized Amphotericin B Lipid Complex in Invasive Pulmonary Aspergillosis in Paediatric Patients With Acute Leukaemia

Summary: The trial evaluates the overall tolerability of the drug and the efficacy of aerosolised amphotericin B as a lipid complex (ABLC) for primary prophylaxis of invasive pulmonary aspergillosis (IPA) in pediatric patients with acute leukemia undergoing intensive chemotherapy.
Inclusion criteria: inclusion criteria:

 Age: patients between 3 and 18 years.

 Diagnosis of myeloblastic or lymphoblastic AL during intensive chemotherapy.

 Informed consent of parents/guardians and/or assent of the patient has been obtained.

Exclusion criteria: :

 Probable or proven invasive pulmonary fungal infection before entering the trial.

 Previous chronic renal impairment or baseline serum creatinine > 2.5 mg /dL

 Severe hepatic impairment.

 Moderate-severe asthma being treated pharmacologically.

 Antifungal treatment for filamentous fungi in the last 4 weeks.

 Participating or have participated in a clinical trial during the last 4 weeks.

 Mentally retarded

 Known allergy or hypersensitivity to the active ingredient of the study drug or to any of its excipients.

 Any serious concomitant disease that in the investigator's opinion could compromise the completion of the trial or affect the patient's tolerability to this treatment.

 Pregnancy (in women of fertile age).

 Breast-feeding.

 Patients are defined as having probable IFI when their radiological image is suggestive of fungal infection and they have positive antigenemia for Aspergillus. IFI would be proven when the presence of Aspergillus is confirmed in aspirate culture or by lung biopsy.

['Invasive Pulmonary Aspergillosis', 'Lymphoblastic Leukaemia', 'Myeloblastic Leukaemia', 'Lymphoblastic Leukemia', 'Myeloblastic Leukemia']

Invasive Pulmonary Aspergillosis
Lymphoblastic Leukaemia
Myeloblastic Leukaemia
Lymphoblastic Leukemia
Myeloblastic Leukemia


Inflammation in Type 2 Myocardial Infarction

Summary: Type 2 myocardial infarction (MI) is defined as myocardial necrosis that results from an imbalance of myocardial oxygen supply and demand. Although type 2 MI is highly prevalent in patients with critical illness and strongly associated with mortality, the pathophysiology remains poorly understood. Inflammation is central to the development of atherosclerosis, plaque rupture, and other subtypes of MI, but the role of inflammation in type 2 MI and myocardial necrosis has not been defined. The investigators aim to to delineate the mechanistic role of inflammation in myocardial necrosis and type 2 MI complicating critical medical illness.
Inclusion criteria: inclusion criteria:

 ≥21 years of age

 admitted to the Medical Intensive or Coronary Care Units

 sepsis or respiratory failure

 clinically indicated troponin measurement within 24 hours of ICU admission

Exclusion criteria: :

 unstable angina or Type 1 MI

 percutaneous or surgical coronary revascularization within 7 days

 heart failure exacerbation

 primary valvular disorder

 aortic dissection

 infiltrative heart disease or hypertrophic cardiomyopathy

 myocarditis

 pulmonary embolism

 electrocardiogram with >1mm ST segment elevation in two consecutive leads

 serum cardiac troponin >99th percentile URL but no clear rise or fall pattern

 history of chronic inflammatory disease

 use of therapeutic-dose anticoagulants / antiplatelet agents other than aspirin

 pregnant or incarcerated

 enrolled in a competing study

['Myocardial Infarction', 'Inflammation', 'Critical Illness']

Myocardial Infarction
Inflammation
Critical Illness


The Prospective Study of Standard Treatment of Graves Disease Iodine 131 and Prevention of Adverse Reactions

Summary: Iodine 131 (131I） treatment on Graves disease and Graves ophthalmopathy relationship has always been the focus of debate. Majority view is that the current treatment does not increase 131I Graves ophthalmopathy, therefore,Graves disease associated with exophthalmos is not a contraindication of 131I treatment. While treatment with corticosteroids, a timely corrective measures to be effective in preventing Graves ophthalmopathy adverse effects. But the merger with severe proptosis in patients with Graves , especially infiltrative exophthalmos , the application of 131I treatment will induce or aggravate not yet reached consensus, so, the 131I treatment is still very careful , mainly due to plaque prospective study and visual assessment is not lack of uniform standards, and a variety of factors (including smoking, work status, and 131I treatment of thyroid doses, etc.) may also interfere or influence the ultimate effect of 131I on the Graves ophthalmopathy. In the view of this situation Graves disease patients with Graves ophthalmopathy could be 131I treatment or not, how to dose adjustments, and the use of which required treatment with systemic issues such as research, explore treatment exophthalmos reduction and mitigation of increased proptosis reasonable treatment of symptoms. To further promote the standardization of 131I treatment of Graves disease on basis.
Inclusion criteria: inclusion criteria:

 a typical clinical symptoms of Graves disease, diffuse goiter, eye signs (including exophthalmos), thyroid function (FT3, FT4, rTSH) and thyroid autoantibodies and imaging examinations to confirmed.

Exclusion criteria: :

 131I treatment contraindications, those who have not signed the informed consent, failure to complete treatment and follow-up estimates of patients and patients not suitable for radionuclide therapy


Multi MERCI (Mechanical Embolus Removal in Cerebral Ischemia [MERCI™])

Summary: The primary objectives of the Multi MERCI trial were:~to evaluate the addition of the Merci L5 Retriever~additionally permit use of the Merci Retrieval System in the setting of persistent clot following IV t-PA treatment (use in the 0-8 hour window for patients ineligible for IV t-PA was also permitted)
Inclusion criteria: inclusion criteria:

 Angiographically confirmed large vessel ischemic stroke (occlusion may include the following: internal carotid artery (ICA), M1/M2, vertebral, or basilar arteries)

 Intervention is able to be performed within 8 hours of symptom onset

 Patients > 18 years of age

 NIHSS score 8+

 Failed IV t-PA treatment or contraindicated for IV t-PA

Exclusion criteria: :

 International Normalized Ratio (INR) > 3.0

 Platelet count < 30,000

 Heparin use in previous 24 hours with PTT > 2X normal

 Baseline bloog glucose < 50 mg/dL

 Baseline computed tomography (CT) showing mass effect with midline shift

 Severe sustained hypertension (SBP > 185 or DBP > 110) that cannot be controlled with medication

 Patient is pregnant, has anticipated life expectancy < 3 months, or has severe allergy to contrast medium

 Arterial stenosis > 50% proximal to embolus

 Excessive arterial tortuosity that precludes the study device from reaching the target area


Incidence, Long- Term Outcome and Factor Related to Non- Cardiac Postoperative Delirium in Elderly Patients

Summary: The purpose of this study is to determine the incidence, long term outcome and factor related to postoperative delirium in elderly patients after non-cardiac surgery.
Inclusion criteria: inclusion criteria:

 Age >/ 60 years

 American Society of Anesthesiologists (ASA) physical status 1-3

 Undergoing scheduled surgery

 Giving an informed consent

Exclusion criteria: :

 Impaired visual and auditory disturbance

 Cannot communicate with Thai language

 Undergoing neurosurgery


The Optimization of Bioavailability From Iron Supplements: Study 2

Summary: Iron deficiency (ID) with or without anaemia (IDA) is a major public health problem worldwide, especially in women of reproductive age and young children. Iron supplementation is an effective strategy to prevent and treat ID and IDA. There is a lack of data on iron bioavailability from different supplementation regimens and how to optimize bioavailability in a cost-effective and patient-friendly way. The daily supplementation with 1-4 mg Fe/kg body weight for 3 months is reported to be the most effective method to rapidly increase iron stores in subjects with ID and IDA. In IDA patients, medical practitioners often prescribe supplementation regimens with 120 mg iron per day split into 2 doses with 60 mg iron, arguing that the splitting would increase iron bioavailability compared with one single high dose. However, there is no scientific evidence for this assumption; to the contrary, results from a recent study suggest that iron bioavailability from a second supplementation dose of iron after a first supplementation dose of iron is impaired due to increased hepcidin levels. To address this bioavailability issue, the present study will determine iron absorption from 120 mg iron administered for 3 consecutive days and compare it with that from 2 doses of 60 mg iron per day administered for 3 consecutive days. The investigators hypothesize that the iron bioavailability from the single daily dose will be lower than that from the 2 doses. By measuring also hepcidin, this study will provide important insights on the iron bioavailability from a single dose of iron and on the same amount iron split into two doses (b.i.d. administration).
Inclusion criteria: inclusion criteria:

 Female, 18 to 45 years old,

 Serum Ferritin levels <20 µg/L,

 Normal body Mass Index (18.5-25 kg/m2),

 Body weight <65 kg,

 Signed informed consent

Exclusion criteria: :

 Anaemia (Hb < 11.7 g/dL),

 Elevated c-reactive protein or alpha1 glycoprotein concentrations >5.0 mg/L, >1.0 g/L, respectively,

 Any metabolic, gastrointestinal kidney or chronic disease such as diabetes, renal failure, hepatic dysfunction, hepatitis, hypertension, cancer or cardiovascular diseases (according to the participants own statement),

 Continuous/long-term use of medication during the whole studies (except for contraceptives),

 Consumption of mineral and vitamin supplements within 2 weeks prior to 1st supplement administration,

 Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 4 months,

 Earlier participation in a study using stable iron isotopes,

 Known hypersensitivity or allergy to iron supplements,

 Women who are pregnant or breast feeding,

 Intention to become pregnant during the course of the studies,

 Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.

 Known or suspected non-compliance, drug or alcohol abuse,

 Inability to follow the procedures of the studies, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,

 Participation in another study with investigational drug within the 30 days preceding and during the present studies,

 Enrolment of the investigator, his/her family members, employees and other dependent persons

['Single oral iron dose of 120 mg per day for 3 consecutive days', 'Two oral iron doses of 60 mg per day (morning + afternoon) for 3 consecutive days']

['Iron Deficiency', 'Anemia', 'Iron Deficiency Anemia']

Iron Deficiency
Anemia
Iron Deficiency Anemia


Evaluation of Mental Flexibility Through Language Tests in Adolescents With Frontal Brain Damage and in Healthy Children in Ages 8-17

Summary: This study aims to shed light on the theoretical concept of mental flexibility and its manifestation in adolescents following frontal lobe damage, and to develop a test battery for young Hebrew speakers.
Inclusion criteria: inclusion criteria:

 frontal lobe damage

 at least one year after injury

 native hebrew speaker

Exclusion criteria: :

 specific language disorder

 premorbid learning disability

['Persons With Frontal Lobe Damage With no Specific Language Disorder']


A Prospective Pilot Study to Evaluate a New Marker of Ischemia in Chest Pain Triage

Summary: A Single-center prospective pilot study enrolling chest pain patients. CD 26 measurement will be performed and compared to troponin µs for early triage of these patients. This novel biomarker of myocardial ischemia (CD26) will be measured at the time of first medical contact (T0) and after 30 min simultaneously o troponin Ic.~All patients aged over 18 years with chest pain which may be related to acute coronary syndrome requiring pre hospital medical contact through the Emergency Medical Service.
Inclusion criteria: inclusion criteria:

 Subject with compatible symptoms with an acute coronary syndrome, for at least 15 minutes and not older than 3 hours (eg discomfort, tightness or chest pain, pain radiating to the left arm or two arms, pain in the jaw, pain in the back / neck / stomach, breathlessness , cold sweats, nausea / vomiting , dizziness )

 Man or woman,

 Patient Did not receive heparin or low molecular weight heparin (LMWH ) before the initial blood sample ,

 Patient Agreeing to participate in the study and who signed an informed consent

Exclusion criteria: :

 Minor or major patient trust

 Patient Not having signed informed consent (refusal , physical or mental disability ... )

 Patient Who received anticoagulation before carrying blood samples

 Patient With a progressive septic processes , neoplasia undergoing treatment, dialyzed kidney failure, a history of surgery or coronary angioplasty less than six months.

 Transplanted heart, renal or hepatic

 heart attack

 Subject Whose symptoms clearly eliminates acute coronary syndrome ( penetrating trauma, traumatic injury by crushing ... )

 Patient Died between the time of inclusion and arrival in the cardiology intensive care ( SIC )

 Patient Withdrawing consent under study


Study of Current Practice Evaluating the Efficacy of a Mobile Short Message Service (SMS) on Post-fracture Management.

Summary: The purpose of the study is to show that the standardized sending of SMS improve the bone mineral density (BMD) screening of patients seen in the Emergency department for low trauma fracture.
Inclusion criteria: inclusion criteria:

 Patients of more than 50 years old

 Low trauma non vertebral fracture

 Ambulatory patient

 Direct access to mobile phone (or access with the help of a close person) and ability to communicate via SMS.

 Patient who doesn't oppose to his participation in the study

 Affiliation to the social security

Exclusion criteria: :

 Patients hospitalized for the fracture in the orthopaedics department because these more severe patients have a systematic screening and management of osteoporosis.

 Fractures whose location is not suggestive of osteoporotic fracture (cervical spine, skull, hands, fingers, toes)

 Pathological fractures (cancer or myeloma)

 Traumatic fractures

 Severe alterations of cognitive functions

 Resident subjects except Paris and the surrounding area


Prevention of Coronary Aneurysms in Kawasaki Syndrome

Summary: To test the efficacy of intravenous gamma globulin (IVGG) in preventing coronary artery aneurysms in children with Kawasaki Syndrome.
Inclusion criteria: Boys and girls who met the CDC criteria for Kawasaki Syndrome. Subjects were excluded if they presented themselves to the participating centers after the tenth day of illness.
Exclusion criteria:

['Cardiovascular Diseases', 'Coronary Aneurysm', 'Heart Diseases', 'Mucocutaneous Lymph Node Syndrome']

Cardiovascular Diseases
Coronary Aneurysm
Heart Diseases
Mucocutaneous Lymph Node Syndrome


Immunogenicity and Safety of the Japanese Encephalitis Vaccine IC51 (IXIARO®, JESPECT®) in a Pediatric Population in Non-endemic Countries

Summary: The primary objective is to assess the safety profile of IC51 in a pediatric population from regions where JEV is not endemic
Inclusion criteria: inclusion criteria:

 Male or female healthy children and adolescents aged >=2 months to <18 years at the time of first vaccination

 Written informed consent by the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable

 Female subjects: either no childbearing potential or negative pregnancy test. For females after menarche willingness to practice a reliable method of contraception.

 The subject is planning to travel to an area where JE is endemic after completion of the vaccination schedule. Exposure to JE should be avoided until 1 week after the second IC51 dose and subjects should return from travel to JE endemic areas before the Month 7 visit. The planned travel to JE endemic areas should not interfere with the study visits and can take place between Visit 2 + 7 days to Month 7.

Exclusion criteria: :

 Clinical manifestation or history of any Flavivirus disease

 Vaccination against JE (except within this protocol), Yellow fever, West Nile virus and Dengue at any time prior or during the study

 History of immunodeficiency or immunosuppressive therapy

 Known HIV, HBV or HCV infection

 History of hypersensitivity reactions to other vaccines

 Acute febrile infection at each visit during which the subject receives a vaccination

 Active or passive immunization within 1 week before and 1 week after each IC51 vaccination.


Randomized Controlled Trial (RCT) in Children With Severe Pneumonia

Summary: Pneumonia is the leading cause of childhood morbidity and death in many developing countries including Bangladesh, causing about 2 million deaths worldwide each year. Pneumonia is an infection of the lungs, most commonly caused by viruses or bacteria like Streptococcus pneumoniae and Haemophilus influenzae. Depending on the clinical presentation, pneumonia can be classified as very severe, severe or non-severe, with specific treatment for each of them except for antibiotic therapy. Severe and very severe pneumonia require hospitalization for additional supportive treatment such as suction, oxygen therapy and administration of bronchodilator. In Bangladesh, the number of hospital beds is inadequate for admission of all pneumonia cases that require hospitalization; however, it is also important to provide institutional care to those children who cannot be hospitalized due to bed constraints. Provision of appropriate antibiotics and supportive cares during the period of stay at established day-care centres could be an effective alternative. The impetus for this study came from the findings of our recently completed study titled Daycare-based management of severe pneumonia in under-5 children when hospitalization is not possible due to the lack of beds. This study successfully managed children (n=251), but it was not a randomized trial and thus direct comparison of the efficacy of management of severe pneumonia at the day-care centre, essential for building confidence for implementing this management policy, is not possible. We, the researchers at the International Centre for Diarrhoeal Disease Research, Bangladesh, could not plan a randomized, controlled trial (RCT) because of ethical reasons. Now that we have data suggesting effectiveness as well as safety of the day-care based treatment for management of children with severe pneumonia, a RCT should be possible. Two hundred fifty-one children with severe pneumonia were enrolled at the Radda Clinic from June 2003 to May 2005. The mean age was 7±7 (2-55) months, 86% infants, 63% boys and 91% breast-fed. History of cough was present in 99% cases, fever in 89% and rapid breathing in 67% cases. Forty-four percent of children were febrile (≥38°C), 93% children had vesicular breath sound and 99% bilateral rales. Fifty-seven percent of children were hypoxic with mean oxygen saturation of (93±4)%, which was corrected by oxygen therapy (98±3)%. Eighty percent of children had severe pneumonia and 20% had very severe pneumonia. The mean duration of clinic stay was (7±2) days. Two hundred thirty-four (93%) children completed the study successfully, 11 (4.4%) referred to hospitals (only one participant had to visit hospital at night due to deterioration of his condition, 9 were referred to hospital at the time of clinic closure i.e., at 5 pm and one participant was referred to hospital during the morning hours) and 6 (2.4%) left against medical advice (LAMA). There was no death during the period of clinic stay but only four (1.6%) deaths occurred during the 3 months follow-up. The study indicated that treatment of severe pneumonia in children at the day-care centre is effective and safe and thus it is comparable to the hospital care. If the day-care based management is found to have comparable efficacy to that of hospitalized management of severe pneumonia in children then they could be managed at outpatient, day-care set ups reducing hospitalization and thus freeing beds for management of other children who need hospitalized care. Additionally, availability of the treatment facility in community set-ups will be cost and time saving for the population. Children of either sex, aged 2-59 months, attending the Radda Clinic and Institute of Child Health and Shishu Hospital (ICHSH) with severe pneumonia will be randomized to receive either the day-care management at the clinic or hospitalized management at the ICHSH. Children randomized to receive day-care treatment will stay at the clinic from 8 am-5 pm and will receive antibiotics and other supportive cares. At 5 pm, they would be send to respective homes with advice to bring back their children to the clinic next morning, and advised to provide other supports at home. The same management would be continued till improvement and discharged and followed up every 2 weeks for 3 months. Children randomized to receive hospitalized management would be admitted at ICHSH and receive standard treatment like antibiotics and other supportive cares. The same treatment would be continued for 24 hours/day (rather than 9 hours/day at the day-care clinic) till improvement and discharged and followed-up at the ICHSH every 2 weeks for 3 months. About 3000 children with pneumonia visit Radda Clinic each year and about 200 of them will have severe pneumonia requiring hospitalization. Thus, we hope to enroll 368 (184 in each site) children with severe pneumonia during a 2-year study period.
Inclusion criteria: inclusion criteria:

 Age: 2 to 59 months

 Sex: Both boys and girls

 Severe pneumonia according to WHO criteria (Severe pneumonia is defined as cough or difficult breathing with lower chest wall in drawing with or without fast breathing which is defined as the respiratory rate ≥ 50 breaths per minute for children aged 2-11 months and ≥ 40 breaths per minute for children aged 12-59 months)

 Attend the Radda Clinic and ICHSH between 8:00 am to 4:00 pm (Sunday through Saturday)

 Written informed consent by respective parents/guardians

Exclusion criteria: :

 Very severe and non-severe pneumonia

 Nosocomial pneumonia

 History of taking antibiotics for pneumonia within 48 hour prior to enrollment

 Chronic illnesses like tuberculosis, cystic fibrosis

 Congenital deformities/anomalies e.g. Down's Syndrome, congenital heart disease

 Immunodeficiency

 Trauma/burn

 Bronchiolitis

 Bronchial asthma

 Lives far away from the Radda Clinic and ICHSH (outside 5 km radius from the respective study site)

 Parents/guardians not consenting for inclusion of their children in the study

['Day-care treatment vs. hospital care']


A Randomized Controlled Trial of Lung Ultrasound Compared to Chest X-ray for Diagnosing Pneumonia in the Emergency Department

Summary: The primary objective of this study is to determine if lung ultrasound (LUS) can replace chest x-ray (CXR) when evaluating patients with possible pneumonia. Specifically, we are looking for an overall reduction of CXR when LUS is used first. Our null hypothesis is that LUS cannot replace CXR for diagnosing pneumonia. Our alternate hypothesis is that LUS can replace CXR for diagnosing pneumonia. Our secondary objectives include: (1) a comparison of unscheduled healthcare visits after the index Emergency Department (ED) visit between those subjects who undergo CXR first and those who undergo LUS first, (2) an evaluation of the rate of antibiotic use between the two groups, (3) a comparison of the admission rates, and (4) a comparison of the length of stay in the Emergency Department between the two groups.
Inclusion criteria: inclusion criteria:

 All patients who present to the ED with respiratory symptoms suspicious for pneumonia

 In whom the treating physician believes would benefit from diagnostic imaging

Exclusion criteria: :

 Patients who arrive at the ED with a previously performed CXR

 Unstable patients with life-threatening injuries who require ongoing resuscitation


Ambien CR For Treatment Of Insomnia Associated With Depression When Used Concomitantly With Lexapro

Summary: To demonstrate overall improvement of insomnia in subjects treated with zolpidem tartrate extended-release (Ambien CR) and escitalopram (Lexapro) vs. subjects treated with placebo and escitalopram at 2 months.
Inclusion criteria: MAJOR inclusion criteria:

 Must experience sleep disturbances at least 3 nights/week, based on historical data

 Must meet the diagnostic requirements for Major Depressive Disorder

 Must have QIDS-SR16 score between 6 and 15

 Must be either newly diagnosed or show symptoms of relapse/recurrence of depression while not on medication

 Age 21-64, inclusive

 Women must use a medically acceptable form of contraception (steroidal contraceptive, double-barrier, or intra-uterine device) during the entire study period, or: be surgically sterilized, post-menopausal, agree to use double-barrier contraception throughout the study period, or must have a negative urine pregnancy test prior to randomization.

 Subject must be stabilized on all ongoing long-term medication therapy for at least 28 days prior to screening visit.

 MAJOR
Exclusion criteria: :

 Severity of depressive episode had been rated as severe or severe with psychotic features.

 History of a suicide attempt or suicidal ideation.

 History of mania, manic episode or bipolar disease.

 Currently using a benzodiazepine or SSRI or more than 2 days of use within the 28 days preceding randomization.

 Use of prescription and non-prescription sedative drugs given for the purpose of sleep induction or to relieve jet lag

 Any abnormal pre-study laboratory values that require clinical intervention

 Prior failure to respond to escitalopram therapy for depression

 Current depressive episode requiring inpatient hospitalization.

 Shift work or requirement for a regular change in sleep schedule by at least six hours within the previous 28 days.

 History of drug addiction, alcoholism, or drug abuse.

 A positive urine drug screen for medication that would interfere with the assessment of the study medication.

 Known allergy to zolpidem, escitalopram or any of their excipients

 History of sleep apnea

 History of myasthenia gravis

 The presence of any untreated or uncompensated clinically significant renal, endocrine, gastrointestinal, hepatic, respiratory, cardiovascular, other neurologic, hematologic, oncologic, immunologic, cerebrovascular disease or malignancy.

 Pregnant or breastfeeding

 Subject is participating in another clinical trial, or has completed another clinical trial within 28 days prior to screening.


Study Evaluating Pantoprazole in Peptic Ulcer Hemorrhage

Summary: The purpose of this study is to evaluate the efficacy and safety of intravenous pantoprazole in the prevention of rebleeding in patients with bleeding peptic ulcer disease after successful endoscopic hemostatic therapy.
Inclusion criteria: inclusion criteria:

 Patients must be men or non-pregnant women at least 18 years of age

 Patients who present with a gastric or duodenal ulcer

Exclusion criteria: :

 Patients with ulcer appearance of clean base (non-oozing, non-spurting) or flat pigmented spot; adherent clots not removed by irrigation

 Patients presenting with active bleeding and/or NBVV at 2 or more separate sites

 Patients with any severe concomitant diseases, eg, end stage liver or renal disease, or unstable cardiovascular, pulmonary, renal, hepatic, or gastrointestinal diseases


Anti-PD 1 Brain Collaboration for Patients With Melanoma Brain Metastases

Summary: The purpose of this research project is to test the effectiveness of nivolumab versus nivolumab together with ipilimumab for the treatment of melanoma brain metastases.~Patients are eligible to join this study if they are aged 18 years or above and have been diagnosed with melanoma with brain metastases.
Inclusion criteria: Cohort 1 and 3

 inclusion criteria:

 ≥18 years of age.

 Written informed consent

 AJCC Stage IV (any T, any N, M1c) histologically confirmed melanoma or unknown primary melanoma. Patients must have at least 1 radiological definitive brain metastasis that is ≥ 5mm and ≤40mm measurable per RECIST version 1.1 guidelines.

 In patients with prior BRAF inhibitor treatment, intracranial disease progression must be demonstrated (RECIST >20% or new measurable brain metastases) compared with nadir of intracranial response during BRAF inhibitor treatment, and confirmed with a second MRI brain scan at any time from the beginning of the drug washout period (dabrafenib=5 days, trametinib=14 days).

 No prior localised treatment for brain metastases (eg. surgery or radiotherapy).

 Neurologically asymptomatic from brain metastases.

 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2, and life expectancy > 30 days.

 Able to undergo MRI with Gadolinium contrast agent.

 Adequate haematological, hepatic and renal organ function.

 Women of childbearing potential: negative serum pregnancy test and effective contraception from 14 days prior to study treatment until 23 weeks after the last dose.

 Men with female partner of childbearing potential to use effective contraception from 14 days prior to study treatment until 31 weeks after the last dose.

Exclusion criteria: :

 Any melanoma brain metastasis >40mm.

 Ocular melanoma.

 Prior treatment with an anti-PD-1 or anti-PD-L1 , anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

 Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

 Current systemic treatment with corticosteroids, except prednisone at nonimmunosuppressive doses of ≤ 10 mg/day (or equivalent). Past treatment for non-neurological symptoms allowed, if ceased 2 weeks prior to starting study treatment. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient on a stable dose. Non-absorbed intraarticular steroid injections will be permitted.

 Any investigational drug or other systemic drug therapy for melanoma within 28 days or 5 half-lives from baseline.

 Known to be HIV positive, or a positive test for hepatitis B and C .

 Another malignancy or concurrent malignancy unless disease-free for 3 years.

 Serious or unstable pre-existing medical conditions or other conditions that could interfere with the patient's safety, consent, or compliance.

 Pregnant or breastfeeding females.

 Administration of any form of live vaccination (such as influenza vaccine) within 30 days of starting trial and anticipated use during the trial. Administration of any other vaccine is cautionary within 30 days of starting the trial and during the trial.

 Cohort 2 - per Cohorts 1 & 3, except patients must have at least one of the following:

 Failed prior local therapy for brain metastases (including surgery, stereotactic radiotherapy or whole brain radiotherapy) where disease has progressed per RECIST (>20% increase in SOD or new measurable brain metastases),

 and/or;

 Have current neurological symptoms related to brain metastases. IF they have received prior local therapy for brain metastases, the disease must have progressed per RECIST (>20% increase in SOD or new measurable brain metastases),

 and/or;

 Have leptomeningeal disease concurrently with measurable brain metastases. IF they have had failed prior local therapy for brain metastases, this must have progressed per RECIST (>20% increase in SOD or new measurable brain metastases).