Safety and Efficacy Study of Inhaled AmBisome for Prevention of Aspergillus Colonization in Lung Transplant Recipients

Summary: Lung transplant recipients have the highest rate of Invasive Aspergillus (IA)infection among solid organ transplant recipients. The most important risk factor for the development of IA (which is associated with disease and death) is colonization of the organism in the respiratory tract.~Azoles are used to prevent the development of IA. Puffers containing antifungal medication can be used to treat the lungs without the need to worry about the medication interactions & side-effects in the blood. An example of this is the aerosolized amphotericin B. Its use is limited by the patients' tolerating this medication that may cause cough, nausea & contraction of the air pathways.~The lipid preparation is better tolerated and has longer dosing interval than inhaled amphotericin B. The investigators propose a pilot study to determine the long-term safety of inhaled AmBisome administration of drug and generate the preliminary data on the effectiveness of this drug to prevent aspergillus colonization.
Inclusion criteria: inclusion criteria:

 Single or double lung transplant recipients who are at least one year out of transplantation.

 Age >18yrs of age

 Able to understand and complete informed consent.

Exclusion criteria: :

 Pregnant woman or woman capable of bearing children, who will not perform urine pregnancy test.

 Nursing mothers.

 Subjects with hypersensitivity to Amphotericin deoxycholate or liposomal Amphotericin.

 Subjects with a past history of bronchospasm associated with aerosol drug use.

 Subjects with active bacterial or viral infection as defined by the current use of non-prophylactic antibiotic anti-viral medications.

 Subjects treated with cytolytic medications (Campath /Thymoglobulin) within the last month.

 Subjects with an FEV1< 30% Predicted or FVC% <30%.

 Subjects requiring supplemental oxygen.

 Receipt of Inhaled or IV Amphotericin B within last 30 days.

 Subjects with known fungal infection as per MSG Criteria on therapy with antifungal drugs or diagnosed on the day of bronchoscopy.

 Current use of azoles active against molds (Voriconazole, itraconazole, posaconazole) for the prophylaxis.

 Serum creatinine > 150 mmol/L on the day of clinic visit.

 Liver enzymes ALT/ AST/ Alkphos greater than two times upper limit of normal.

 Concurrent intravenous aminoglycoside use.

 Subjects with fever > 38.2°C.

 Subjects on mechanical ventilation.

 Expected survival less than 6 months.

 Re-transplants and heart/lung transplant patients.

['Ambisome ®', 'Regular standard of care medication']

Ambisome ®
Regular standard of care medication


Efficacy and Safety of Escitalopram for Prevention of Depression Induced by Peg-Interferon in Hepatitis C Patients

Summary: The purpose of this study is to determine whether the use of an antidepressant (escitalopram) can prevent depressive episodes that appear during the treatment with peg-interferon and ribavirin in patients with chronic hepatitis C.
Inclusion criteria: inclusion criteria:

 Patients with chronic hepatitis C who are going to initiate treatment with peginterferon alfa2a + ribavirin.

 Age 18-65 years.

 Signed informed consent.

 If female, they are not in fertile period or they use barrier contraceptives.

 Patients able to understand and fill written questionnaires.

Exclusion criteria: :

 Hepatic cirrhosis or carcinoma.

 Less than 4000/mm3 leucocytes, or less than 70000/mm3 platelets.

 Hemoglobin less than 11 g/dL (females) or 12 (males).

 Any risk factor for hemolysis.

 Comorbid severe medical conditions (kidney, immune system, lung, heart, thyroid, etc).

 Baseline mental disorders that require antidepressants (depressive disorders and anxiety disorders).

 Other baseline mental disorders (delirium, substance use disorders).

 Mental disorders at any time (dementia, psychotic disorders, bipolar disorders.

 Contraindications of escitalopram (hypersensibility, diabetes, patients using serotoninergic agents, drugs that enhance the risk of bleeding, or monoamineoxidase inhibitors -MAOIs-).

['Major Depressive Disorder', 'Hepatitis C, Chronic']

Major Depressive Disorder
Hepatitis C
Chronic


Efficacy of Cantharidin in Molluscum Contagiosum

Summary: The University of North Carolina Department of Dermatology is conducting a clinical trial to evaluate a drug called cantharidin in the treatment of molluscum contagiosum. Molluscum is a common dermatologic disorder caused by a poxvirus. Molluscum typically presents with many flesh-colored bumps on the skin. It goes away on its own, though can last several months to several years. Cantharidin is a topical medicine which is applied at the clinic visit. It is well tolerated by the majority of children.
Inclusion criteria: inclusion criteria:

 Anyone aged 5-10 years with the clinical diagnosis of molluscum contagiosum.

Exclusion criteria: :

 Anyone with immunosuppression including HIV or previous organ transplantation.

 Anyone taking immunosuppressive medications.

 Anyone who has previously received treatment with cantharidin.

 Any female who has had her first menstrual period.

["cantharidin's vehicle", 'Cantharidin 0.7%']


ASIS for Botox in Upper Limb Spasticity

Summary: Botox act on nerve endings, yet there are no nerve endings inside the muscle, where they are typically injected. All nerves terminate on the fascia, where ASIS device can precisely deliver Botox by creating that subdermal bloodless space, between the skin and muscle. Thus enhancing and prolonging Botox's efficacy, at the same time prevent it's unnecessary adverse reactions and distant spread, especially since Botox has no reason to travel to the rest of the body any way.
Inclusion criteria: inclusion criteria:

 Adults with history of stroke that resulted in a unilateral, upper-limb focal spasticity

 Wrist flexor tone of more than 2 and finger flexor tone of more than 2 as measured by the Ashworth Scale

 Ability to understand and follow verbal directions

 At least 1 functional disability item (hygiene, dressing, pain, or limb posture) with a rating of more than 2 on the Disability Assessment Scale (DAS)

 At least 1 functional task score at Day 0 that met the following criteria: nail filing less than 6, hand cleaning less than 6, holding a water bottle less than 4, brushing teeth less than 4, holding fruit (small, medium, or large equals no.

Exclusion criteria: :

 Stroke within 6 months of the study enrollment visit

 Females who are pregnant, nursing, or planning a pregnancy during the study period or who are not using a reliable means of contraception

 Previous or current Botox therapy of any type in the study limb

 Any medical condition that may put the patient at increased risk with Botox exposure or any other disorder that might have interfered with neuromuscular function

 Presence of fixed contracture of the study limb

 Limited use of the wrist and fingers

['Gadolinium', 'Gadolinium', 'Gadolinium', 'Efficacy of Botox intramuscularly at Week 6', 'Efficacy of Botox intramuscularly at Week 12,', 'Efficacy of Botox intramuscularly at Week 18', 'Efficacy of Botox intramuscularly at Week 24', 'Efficacy of Botox intramuscularly at Week 30', 'Efficacy of Botox subdermally at Week 6', 'Efficacy of Botox subdermally at Week 12', 'Efficacy of Botox subdermally at Week 18', 'Efficacy of Botox subdermally at Week 24', 'Efficacy of Botox subdermally at Week 30', 'Adverse Reactions of Botox intramuscularly', 'Adverse Reactions of Botox subdermally']

['Upper Limb Spasticity Unilaterally in Adults With History of Stroke', 'Increased Muscle Tone in Elbow, Wrist, Finger, and Thumb Flexors.']


Inflammatory Response Following Intraarticular Fracture

Summary: The purpose of the study is to investigate a relationship between the inflammatory response following intraarticular fracture and post-traumatic osteoarthritis. The investigators plan to evaluate the inflammatory cytokine profile in knee joint synovial fluid and blood serum in patients who sustain an intraarticular tibial plateau fracture and ankle joint synovial fluid and blood serum in patients who sustain an intraarticular tibial plafond fracture. This information will be combined with radiographs and patient outcome measures to determine a correlation between intraarticular inflammatory response and post-traumatic osteoarthritis.
Inclusion criteria: inclusion criteria:

 18 years of age or older

 Radiographic evidence of tibial plateau fracture

Exclusion criteria: :

 Less than 18 years of age

 Greater than 60 years of age

 Any history of pre-existing knee osteoarthritis based on previous diagnosis or suggestive history

 Any history of autoimmune disease

 Any history of contralateral intra-articular knee injury

['Intraarticular Fracture and Post-traumatic Osteoarthritis']


Studies of the Ocular Complications of AIDS (SOCA) CMV Retinitis Trial: Foscarnet-Ganciclovir Component

Summary: To evaluate the relative effectiveness and safety of foscarnet versus ganciclovir for the treatment of cytomegalovirus (CMV) retinitis in people with AIDS; to evaluate the relative effect on survival of the use of these two anti-CMV agents in the treatment of CMV retinitis; to compare the relative benefits of immediate treatment with foscarnet or ganciclovir versus deferral of treatment for CMV retinitis limited to less than 25 percent of zones 2 and 3.~CMV retinitis is a common opportunistic infection in patients with AIDS. Ganciclovir is currently the only drug approved for treatment of CMV retinitis in immunocompromised patients. Ganciclovir suppresses CMV infections, and relapse occurs in virtually all AIDS patients when ganciclovir is discontinued. Because of their similar hematologic (blood) toxicities, the simultaneous use of ganciclovir and zidovudine (AZT) is not recommended. More recently the drug foscarnet has become available for investigational use. Studies so far indicate that remission of CMV retinitis occurs in 36 to 77 percent of patients, and that relapse occurs in virtually all patients when the drug is discontinued. The relative effectiveness of foscarnet compared with ganciclovir for the immediate control of CMV infections is unknown. Further, the long-term effects of foscarnet or ganciclovir on CMV retinitis, survival, and morbidity are unknown. There is also no definitive information on the relative effectiveness and safety of deferred versus immediate treatment for CMV retinitis confined to zones 2 and 3.
Inclusion criteria: inclusion criteria

 Concurrent Medication:

 Allowed:

 Topical anti-Herpesvirus agents.

 Zidovudine (AZT) for patients in deferral or foscarnet treatment groups:

 100 mg every 4 hours. For patients on ganciclovir:

 100 mg every 8 hours.

 Dideoxyinosine (ddI) and other antiretroviral available via expanded access programs, investigational triazoles, granulocyte-macrophage colony-stimulating factor, and erythropoietin to treat marrow toxicity. The use of other investigational drugs will be considered on a drug by drug basis.

 It is not recommended that patients receiving ganciclovir take AZT simultaneously. If AZT is prescribed for patients taking ganciclovir, it should be prescribed at reduced doses and discontinued if hematologic toxicity develops.

 Patients must have:

 Diagnosis of AIDS by CDC criteria or a documented HIV infection.

 Cytomegalovirus (CMV) retinitis that does not require surgical intervention diagnosed in one or both eyes by a SOCA-certified ophthalmologist.

 The means available for compliance with follow-up visits (including a caregiver if necessary).

 Must consent to study or consent of parent or guardian if less than 18 years of age.

 Willingness to take reduced dose of zidovudine (AZT) if dictated by treatment assignment.

 Willingness to discontinue other systemic treatments for Herpesvirus infections while receiving foscarnet or ganciclovir.

 Prior Medication:

 Allowed:

 Zidovudine (AZT).

Exclusion criteria:

 Co-existing Condition:

 Patients with the following conditions or symptoms are excluded:

 Sufficient media opacities to preclude fundus photographs in both eyes.

 Concurrent Medication:

 Excluded:

 Other systemic treatments for Herpesvirus infections.

 Other anti-cytomegalovirus therapy.

 Excluded with foscarnet:

 Parenteral pentamidine, amphotericin B, or aminoglycosides.

 Use of marrow toxic agents with ganciclovir and nephrotoxic agents with foscarnet is discouraged, and alternative treatment should be used whenever possible.

 Patients with the following are excluded:

 Sufficient media opacities to preclude fundus photographs in both eyes.

 Known or suspected allergy to one of the study medications.

 Prior Medication:

 Excluded:

 Foscarnet or ganciclovir used previously to treat cytomegalovirus (CMV) retinitis.

 Excluded within 14 days of study entry:

 CMV hyperimmunoglobulin or other anti-CMV agents.

 Excluded within the past 28 days:

 Anti-CMV therapy.

 Active intravenous drug or alcohol abuse, sufficient in the investigator's opinion to prevent adequate compliance with study therapy and follow-up.

['Cytomegalovirus Retinitis', 'HIV Infections']

Cytomegalovirus Retinitis
HIV Infections


Effect of Prophylactic Clip Application for the Prevention of Postpolypectomy Bleeding in Pedunculated Colonic Polyps

Summary: Although endoscopic colonic polypectomy has been an established procedure for two decades, the risk of bleeding is still higher after resecting of pedunculated polyps, because of the presence of a large artery in the stalk. Preventive methods such as endoloop and epinephrine injection have been proposed in the management of postpolypectomy bleeding in large colonic polyps. For prophylactic clip, there was no randomized controlled study assessing the efficacy in the prevention of postpolypectomy bleeding for the large pedunculated polyps. So the investigators designed a randomized controlled trial to confirm the efficacy of application of prophylactic clip in the prevention of postpolypectomy bleeding in large polyps.
Inclusion criteria: inclusion criteria:

 Patients with pedunculated colorectal polyps, the heads of which were larger than 10mm and the stalk of which were large than 5 mm in diameter, were included.

Exclusion criteria: :

 bleeding tendency, poor preparation, sessile polyp

['Prophylactic clip', 'No prophylactic management']

Prophylactic clip
No prophylactic management


Numen Stent Assessment Using OCT Technique in a Single Center Study

Summary: This is a prospective single centre Study designed to assess by OCT the effect of NUMEN cobalt-chromium balloon-expandable stent in inducing neointimal hyperplasia in de novo native coronary lesions of patients with Stable Angina Pectoris or ACS (except STEMI).~A total of 60 consecutive patients will be enrolled in the study. Patients with de novo native coronary artery lesions >10mm and <24mm in length and >2.50mm to <3.50mm in diameter by QCA estimate who meet all eligibility criteria will be enrolled and undergone stent implantation. After stent deployment an OCT imaging will be performed within the treated segment. Patients will be followed at 30 days, 6 months and 12 months post-procedure, with all patients having repeat angiography and OCT at 6 months.~It is anticipated that the total length of the study will be 18 months: 6 months to complete patient enrolment and 12 months for follow-up.
Inclusion criteria: inclusion criteria

 Patients must meet all of the following criteria:

 The patient must be > 18 years of age;

 Diagnosis of stable angina pectoris as defined by Canadian Cardiovascular Society Classification (CCS I, II, III, IV) or ACS (except STEMI).

 Treatment of de novo lesion in a major coronary artery in patients with single or two-vessel disease.

 Target vessel diameter at the lesion site is >2.50mm and <3.50mm in diameter (QCA);

 Target lesion is >10mm and <24mm in length (visual estimate);

 Target lesion stenosis is >50% and <100% (visual estimate);

 Acceptable candidate for coronary artery bypass surgery (CABG);

 Patient is willing to comply with the specified follow-up evaluation;

 Patient must provide written informed consent prior to the procedure using a form that is approved by the local Ethics Committee.

Exclusion criteria:

 Patients will be excluded if any of the following conditions apply:

 multiple lesions in the same vessel;

 ACS with STEMI (within 48 hours)

 vessel size < 2.50mm and >3.50mm reference diameter;

 length of the lesion > 24 mm;

 unprotected left main coronary disease with >50% stenosis;

 have an ostial target lesion;

 have a target lesion in a venous graft;

 angiographic evidence of thrombus within target lesion;

 calcified lesion which cannot be successfully predilated;

 Documented left ventricular ejection fraction >25%;

 Impaired renal function (creatinine > 3.0 mg/dl) at the time of treatment;

 Pretreatment with devices other than balloon angioplasty;

 Prior stent within 5mm of target lesion;

 Recipient of heart transplant;

 Known allergies to the following: aspirin, clopidogrel bisulfate (Plavix) and ticlopidine (Ticlid), heparin, cobalt, chromium, or contrast agent (that cannot be managed medically)

 Recent (6 months) cerebrovascular accidents or intracranial hemorrage

 Any significant medical condition which in the investigator's opinion may interfere with the patient's optimal participation in the study;

 Currently participating in an investigational drug or another medical device study;

 In the investigator's opinion, the lesion is not suitable for stenting.

 Life expectancy ≤ 12 months


Memory and Attention Problems in Lupus: New Treatment Trial With Modafinil

Summary: This study is being conducted in order to determine if the FDA-approved drug Modafinil can improve cognitive function in patients with lupus. Modafinil is currently being used to treat excessive sleepiness caused by certain sleep disorders. It has also been shown to improve attention and concentration in some people who don't have lupus or sleep disorders. This study hopes to determine if Modafinil can be used safely and effectively in lupus patients, and improve their quality of life. No medications currently exist for the treatment of lupus-associated cognitive dysfunction.
Inclusion criteria: inclusion criteria:

 Fulfill ACR Classification Criteria for SLE

 >18 and < 60 years old

 English-speaking/reading

 Has a treating rheumatologist at the Hospital for Special Surgery

 Estimated premorbid verbal I.Q. >80 measured by the North American Adult Reading Test

 Functional difficulties due to cognitive dysfunction defined as positive endorsement of ≥6 items on the Cognitive Symptoms Inventory (CSI). The CSI is a 21-item, self-report questionnaire designed to assess ability to perform everyday activities in patients with rheumatic disease.47

 No physical or mental disabilities that would preclude or confound the results of the neuropsychological testing, e.g., compromised use of hands, severe visual or hearing impairment

 Able to read normal newsprint and hear a normal speaking voice

 Normotensive at time of enrollment with or without medication

 No arrhythmia or left ventricular hypertrophy on ECG

 Adequate contraception (barrier method)

Exclusion criteria: :

 Global cognitive impairment as measured by a Modified Mini Mental Status<77

 History of arrhythmia; known history of left ventricular hypertrophy, mitral valve prolapse with syndrome, or other significant cardiovascular disease with a reduced ejection fraction

 Renal insufficiency (creatinine clearance < 30 ml/min) including dialysis patients

 Known liver disease (e.g., active hepatitis) or any liver function test >2x upper limit of normal (transaminases or GGTP)

 Significant and serious SLE activity defined as active central nervous system disease, active nephritis, ulcerative skin disease. Other active SLE-associated conditions involving major organ systems may be excluded at the discretion of the investigator.

 Pregnancy, nursing mother, or unwillingness to use barrier contraception

 Diagnosis of active psychosis, ADHD, ADD

 Current use of medications contraindicated with the use of modafinil-triazolam, Phenobarbital, cyclosporine A, theophylline, carbamazepine, diazepam, phenytoin, mephenytoin, rifampin, ketoconazole, itraconazole,

 Illegal drug or alcohol abuse (defined as two affirmative responses to the CAGE questionnaire)

 Prior use of modafinil


Improved Screening for Osteoporosis

Summary: Osteoporosis is a disease characterized by skeletal fragility due to decreased bone mass and deterioration of bone microarchitecture , leading to increased fracture risk for low trauma, such as spinal fractures or femoral neck .~It is estimated that 3 million people are living in France , particularly women , with an incidence that increases with age .~This disease is a major public health issue in terms of morbidity and mortality , costs and risk of recurrence (after a first fracture episode) , including risk factors are identified.~However, although bone densitometry is a reliable diagnostic tool and preventive treatments are at our disposal, screening for osteoporosis is still insufficient .~The objective of our study is to improve the detection of osteoporosis in Hospital Departmental Vendee , using a simple questionnaire seeking risk factors followed by bone densitometry or if risk factors are found. Based on the results , the patient will be sent in rheumatology consultation for implementation of treatment if necessary .~Therefore included women hospitalized in medical services , gynecology, surgery and orthopedics Hospital Departmental Vendee , aged 50 to 80 years. Will not be included women who could answer a simple questionnaire and those previously treated for osteoporosis or have already received a bone density there is less than 3 years old .
Inclusion criteria: inclusion criteria:

 Women between 50 and 80 years

 Hospitalized

 In health services, orthopedics, gynecology, surgery

 Able to respond to an easy questionnaire

 Able to give their agreement to participate in the study

Exclusion criteria: :

 Patients with dementia

 Patients can not express

 Patients at end of life

 Patients previously treated for osteoporosis or recent densitometry (BMD) <3 years

 Patients could not be seen in time by the nurse during their hospitalization

 Patients receiving a measure of legal protection


Inhaled Prostacyclin for Adult Respiratory Distress Syndrome (ARDS) and Pulmonary Hypertension

Summary: Summary of the proposed research:~The intravenous application of prostacyclin (PGE1) or its stable analogue, iloprost, has been used to cause a decrease not only of the pulmonary but also of the systemic vascular tone. Aerosolized prostacyclin, on the other hand, can result in a selective pulmonary vasodilatation without affecting the systemic blood pressure as shown in preliminary studies/case reports. No large trials exist for this type of use of the drug so far. Furthermore, aerosolized PGI2 can improve gas exchange and pulmonary shunt in clinical settings of impaired ventilation/perfusion ratio as it occurs in adult respiratory distress syndrome (ARDS) due to the redistribution of pulmonary blood flow from non-ventilated to ventilated, aerosol accessible lung regions. Therefore, the investigators propose to carry out a prospective, double blinded, randomized trial to show that the nebulized iloprost decreases pulmonary hypertension selectively and improves oxygenation in ARDS.
Inclusion criteria: inclusion criteria:

 After obtaining informed consent the following patients will be included:

 All patients admitted to the ICU with pulmonary hypertension (mean PA > 35 mmHg).

 All patients in ICU with post operative pulmonary HTN (mean PA > 35 mm Hg).

 All patients with ARDS (PaO2/FiO2 < 200 - arterial hypoxemia, bilateral infiltrates on Chest X-ray infiltrates on CXR and a wedge < 20 mm Hg on swan ganz parameters) or signs of heart failure.

Exclusion criteria: :

 Patients to be excluded will be those with:

 Pulmonary embolus.

 Cor pulmonale.

 Ejection fraction of < 30%, wedge > 20 mm Hg.

 Non-intubated patients.

 Pediatric patients (< 16 yrs of age).

['PGE1 (prostacyclin)', 'normal saline']

['Adult Respiratory Distress Syndrome', 'Pulmonary Hypertension']

Adult Respiratory Distress Syndrome
Pulmonary Hypertension


The TRUST Study - Depression Substudy

Summary: Mild thyroid failure is a common condition among older adults and has been associated with numerous adverse effects on health, such as cardiovascular disease, cognition disturbances and muscular problems. Mild thyroid failure has also been associated with an increased risk of developing depression. To date, only few studies have investigated the effect of thyroid hormone replacement on depression in patients with mild thyroid failure. This study therefore aims to assess whether thyroid hormone replacement in older adults with mild thyroid failure is associated with a decrease in the presence of depressive symptoms. This study forms a substudy of a large international study on thyroid hormone replacement in older adults with mild thyroid failure (the TRUST study).
Inclusion criteria: inclusion criteria:

 Community-dwelling patients aged >= 65 years with subclinical hypothyroidism

 Written informed consent

Exclusion criteria:

 Subjects currently on Levothyroxine or antithyroid drugs, amiodarone or lithium

 Recent thyroid surgery or radio-iodine (within 12 months)

 Grade IV NYHA heart failure

 Prior clinical diagnosis of dementia

 Recent hospitalisation for major illness or elective surgery (within 4 weeks)

 Terminal illness

 Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

 Subjects who are participating in ongoing RCTs of therapeutic interventions (including CTIMPs)

 Plan to move out of the region in which the trial is being conducted within the next 2 years (proposed minimum follow-up period)


Concurrent Treatment for Depressed Parents and DepressedAdolescents

Summary: This study will develop an integrated treatment for adolescents who are depressed and suicidal and their parents who are depressed and have a history of suicidality.
Inclusion criteria: inclusion criteria for Adolescents:

 Lives at home with at least one parent or guardian

 Speaks English

 Must have made a suicide attempt and be diagnosed with major depressive disorder (MDD)

 inclusion criteria for Primary Caretakers:

 Speaks English

 Current diagnosis of MDD and a history of suicidality

Exclusion criteria:  for Adolescents:

 Judged to have developmental or cognitive delays or psychotic disorders on the basis of a standard psychiatric exam

 Diagnosis of bipolar disorder or a substance dependence (people with a diagnosis of substance abuse are eligible)

 Only one adolescent per family is eligible

['Concurrent treatment', 'Adolescent treatment only']

Concurrent treatment
Adolescent treatment only


Nasal Physiologic Reactivity of Nonallergic Rhinitics to Cold Air Provocation

Summary: This study seeks to compare patients with vasomotor rhinitis (perennial nonallergic rhinitis, idiopathic rhinitis) with normal controls with respect to their nasal physiologic reactivity to cold air challenge. Ten vasomotor rhinitis (VMR) patients with nasal symptoms triggered predominantly by cold air, four VMR patients with symptoms triggered predominantly by chemicals, and ten nonallergic, non-rhinitic control subjects will be studied.
Inclusion criteria: inclusion criteria:

 (cases; n = 14 total; 10 with predominantly physical and 4 with predominantly irritanttriggers):

 A significant history of chronic and/or recurrent nasal symptoms (rhinorrhea, blockage,sneezing or pruritus) in response to:

 Changes in temperature and/or humidity predominantly (physical triggers; n = 10); or

 Two or more nonspecific irritant triggers predominantly, including: perfumes or colognes,cleaning products, environmental tobacco smoke, vehicular exhaust, paint odors, etc. (irritant triggers;n = 4). This history shall be of at least two years' duration.

Exclusion criteria: :

 (controls; n = 10):

 A significant history of chronic and/or recurrent nasal symptoms (rhinorrhea, blockage,sneezing or pruritus) in response to one or more nonallergic triggers, including: perfumes or colognes, cleaning products, environmental tobacco smoke, vehicular exhaust, paint odors, changes in temperature and/or humidity.

['Cold-dry air provocation', 'Warm-moist air provocation']

Cold-dry air provocation
Warm-moist air provocation


Household Transmission of Zoonotic Influenza Viruses in a Cohort of Egyptian Poultry Growers

Summary: This study seeks to determine the incidence and transmission of avian influenza viruses in humans exposed to poultry. Enrolled subjects will be selected from five different rural areas (villages) in the Nile delta region in Egypt where poultry are commonly raised. From those study sites, 2400 healthy subjects will be monitored for 6 years with annual follow up visits to measure sero-prevalence and exposure variables, and more importantly, biweekly or weekly visits to measure incidence of infection, measure secondary transmission rates, monitor symptoms, and assess immunological response.~Primary Objectives:~To estimate the incidence of avian influenza (AI) in poultry-exposed human populations.~To estimate sero-prevalent of AI in poultry-exposed human populations.~To investigate potential risk factors associated with AI human infections in poultry-exposed individuals.~To investigate secondary infection risk for household contacts.~Secondary Objectives:~To characterize the antigenic and genetic makeup of AI viruses infecting humans.~To monitor the pathogenicity and disease severity of AI viruses causing human infections and the associated immune response.~To investigate the serologic response following confirmed influenza virus infection.
Inclusion criteria: inclusion criteria:

 Poultry-exposed individuals with poultry in the household willing to participate by signing a consent or assent form as appropriate for age, completing the study questionnaire, and permitting the withdrawal of blood, nasal washes, nasal swabs, and throat swabs.

Exclusion criteria: :

 Any known immunosuppressive condition or immune deficiency disease (including HIV infection), or ongoing receipt of any immunosuppressive therapy. (Note that we have chosen to exclude such populations because of their increased risk of acquiring infections, they are relatively few, and are not representative of a national sample.)

 Terminally ill individuals.

 Children who are less than 2 years old when baseline enrollment is performed.

['Questionnaire', 'Blood sample', 'Nasal wash', 'Throat swab']

Questionnaire
Blood sample
Nasal wash
Throat swab


Treatment of Locally Advanced or Metastatic Transitional Cell Carcinoma With Cabazitaxel

Summary: A study for patients with confirmed locally advanced or metastatic Transitional Cell Carcinoma of the bladder or upper urinary tracts who have developed progressive disease within 12 months of their platinum based chemotherapy. The study aims to compare the overall response rate of cabazitaxel treatment versus best supportive care including single agent chemotherapy.
Inclusion criteria: inclusion criteria:

 Written informed consent

 Age ≥ 18

 Life expectancy ≥ 12 weeks

 Patients with histology/cytology confirmed Transitional Cell Carcinoma (TCC) including mixed pathology with predominantly TCC, with locally advanced (T4b) or metastatic (lymph node or visceral) TCC arising from bladder or upper urinary tracts.

 Treated patients with incidental prostate cancer (pT2, Gleason ≤ 6) and PSA (Prostate Specific Antigen) ≤ 0.5 ng/mL are eligible

 Measurable disease as per RECIST Criteria 1.1

 ECOG Performance Status 0-1.

 Previously received first line platinum based treatment.

 Recurrence within 12 months (by RECIST criteria version 1.1) from last cycle of chemotherapy.

Exclusion criteria: :

 Previous therapy with a taxane.

 Pure non TCC histologies

 Grade II or more peripheral neuropathy

 Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrolment in the study.

 Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)

 Inadequate organ and bone marrow function as evidenced by:

 Hemoglobin < 9.0 g/dL

 Absolute neutrophil count < 1.5 x 109/L,

 Platelet count < 100 x 109/L,

 AST/SGOT and/or ALT/SGPT > 2.5 x ULN;

 Total bilirubin > 1.0 x ULN,

 Serum creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance ≤ 30 mL/min should be excluded (see Appendix 6 for formula)

 Symptomatic brain metastases or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).

 History of another neoplasm except non-metastatic melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery, small field radiation or chemotherapy < 5 years prior to randomization.

 History of inflammatory bowel disease, significant bowel obstruction.

 History of hypersensitivity to platinum, gemcitabine, taxanes, Polysorbate-80, or to compounds with similar chemical structures.

 Any of the following events within 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant arrhythmias (grade 3-4).

 Concurrent treatment with strong inhibitors of cytochrome P450 3A4 or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required prior to randomization.

 Women who are breastfeeding and women of child bearing potential (not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus)) unless in agreement to use an adequate method of contraception during the treatment period and for 6 months after the last dose of the study drug. Men unless in agreement that they will use effective contraception (and condom to protect against exposure to seminal liquid) whilst participating in the trial and for 6 months after the last dose of study medication.


Post-Radioiodine Graves' Management: The PRAGMA-Study

Summary: Thyroid dysfunction following radioiodine for Graves' disease is common, potentially detrimental and avoidable. A variety of clinical strategies are employed in the post-radioiodine era util the patient is on a stable thyroid hormone replacement regimen, which include the use of anti-thyroid drugs, antithyroid drugs with thyroxine, early thyroxine replacement and watchful monitoring until the onset of hypothyroidism. Which of these is most effective in avoiding dysthyroidism, is unknown. This study aims to address this lack of evidence. It will focus on Graves' disease as this is the commonest cause of thyrotoxicosis and the commonest indication for RI therapy. It will provide an insight into potential strategies for improving important clinical outcomes.
Inclusion criteria: inclusion criteria:

 Out-patients 18 years of age or over, who have given written informed consent to participate in the study

 Diagnosed with Graves' disease

 Received radioiodine for treatment of Graves' disease

 Had a minimum of 12 months follow-up after RI

 Most recent RI dose 5 years ago or less at the time of enrollment

Exclusion criteria: :

 Patients unable to give informed consent

 Age 17 years or younger

 Cause of thyrotoxicosis other than Graves' disease

 Patients who have had more than one dose of radioiodine can only be included in the study once, using data pertaining to their most recent treatment episode.

 Patients who might not adequately understand verbal explanations or written information given in English, or who have special communication needs


The HIT-TRAP Trial

Summary: Randomised, double blind trial in non-intensive care trauma patients comparing unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in heparin-induced thrombocytopenia (HIT).
Inclusion criteria: inclusion criteria:

 trauma-surgical patient

 consent given

 minimum age 18

 expected inpatient period at least 7 days

 need for thrombosis prophylaxis with heparin

Exclusion criteria: :

 intolerance of one of the study drugs

 malignancy with life expectancy < 3 months

 pregnancy/lactation

 drug or alcohol abuse

 fibrinolytic therapy

 need for extracorporal circulation (e.g. cardiopulm. bypass, hemodialysis) at study entry

 participation in another clinical trial within 30 days prior to intended inclusion

['Standard heparin (UFH) versus certoparin (LMWH)']


Study Assessing Risk of Autoimmune Diseases in Females (9 - 25 Years) Exposed to Cervarix® in United Kingdom

Summary: This is an observational cohort study to assess the risk of autoimmune disease(s) within 12 months of receiving the first dose of Cervarix® in the exposed cohort and over a comparable period in the unexposed cohorts.~This is an alternative study by GSK using the CPRD database in the UK to fulfil the US FDA safety commitment. The UK has had sufficient Cervarix® vaccination coverage during the period mid-September 2008 to 2011 to allow suitable data to be collected.
Inclusion criteria: inclusion criteria:

 Note: Other vaccines are allowed in this study regardless of the time of administration and the time interval between subsequent doses.

 inclusion criteria for the exposed female cohort:

 Female aged from 9 to 25 years at the reference date (01 September 2008 through 31 August 2010).

 Recorded in the CPRD GOLD for at least 12 months before the reference date.

 The first dose of Cervarix received between 01 September 2008 through 31 August 2010, Full date (day/month/year) of Cervarix vaccination(s) available.

 Subject defined as acceptable in CPRD GOLD.

 inclusion criteria for the unexposed historical female cohort:

 Female aged 9 to 25 years at the reference date (01 September 2005 through 31 August 2007).

 Recorded in the CPRD GOLD for at least 12 months before the reference date.

 Subject defined as acceptable in CPRD GOLD.

 inclusion criteria for the unexposed concurrent male cohort:

 Male aged 9 to 25 years at the reference date (01 September 2008 through 31 August 2010).

 Recorded in the CPRD GOLD for at least 12 months before the reference date.

 Subject defined as acceptable in CPRD GOLD.

 inclusion criteria for the unexposed historical male cohort:

 Male aged 9 to 25 years at the reference date (01 September 2005 through 31 August 2007).

 Recorded in the CPRD GOLD for at least 12 months before the reference date.

 Subject defined as acceptable in CPRD GOLD.

Exclusion criteria: :


Retroperitoneal Packing or Angioembolization for Hemorrhage Control of Pelvic Fractures

Summary: This study is designed to answer whether minimal invasive vessel clotting (angioembolization) or open surgery (retroperitoneal packing) is more effective for pelvic fractures with massive bleeding. Patients admitted at daytime (7am-5pm) are treated with angioembolization while patients admitted at nighttime (5pm to 7am) are treated with open surgery.
Inclusion criteria: inclusion criteria:

 multitrauma defined as Injury Severity Score (ISS) > 17

 dislocated pelvic fracture type B or C according to Tile[10] on emergency department pelvic radiograph

 hemodynamic instability defined as systolic blood pressure (SBP) <90 mmHg after administration of 4 units of packed red blood cells (PRBC).

Exclusion criteria: :

 monotrauma, or ISS ≤ 17

 age > 65 years

 age < 18 years

['Shock, Hemorrhagic', 'Fractures, Bone', 'Multiple Trauma']

Shock
Hemorrhagic
Fractures
Bone
Multiple Trauma


Functional Rehabilitation of Upper Limb Apraxia in Patients Poststroke

Summary: The purpose of this study is to analyze the effects of a mixed intervention of occupational therapy (rehabilitative and compensatory approach) at home to upper limb apraxia in mild and moderate patients post stroke in comparison to a control group with a traditional health educative protocol.
Inclusion criteria: inclusion criteria:

 Mild-moderate stroke after two month of the cerebrovascular attack.

 Upper limb apraxia lasting at least 2 months.

 Less than 9 points in validated Apraxia Screen of TULIA (AST) following Vanbellingen et al., 2010.

 Voluntary participation.

 The neurologist, the occupational therapist and the patient judge the intervention to be necessary.

Exclusion criteria: :

 History of apraxia before current stroke.

 Stroke had occurred less than two months or more than twenty four month ago.

 Cognitive impairment (< 23 in normal school population and < 20 points with a low education or illiteracy, in Spanish validation of Mini-Mental State Examination (MMSE)).

 Severe aphasia.

 Previous brain tumour.

 History of other previous neurologic disorders.

 Mother tongue different to Spanish.

 Drugs addiction.

 Intellectual or learning disorders.

 Brain damage for traumatism or neurodegenerative process.

 A history of serious consciousness impairments

 Uncooperativeness, presence of orthopedic or other disabling disorders.

['Functional Rehabilitation of apraxia', 'Traditional health educative protocol']

Functional Rehabilitation of apraxia
Traditional health educative protocol


Arthrocentesis Study

Summary: The purpose of this study is to analyze pre- and intra-operative joint aspirates of native joints and joints with suspicion of periprosthetic joint infection (PJI) of the hip, knee and shoulder acquired in clinical routine. Joint aspirates are then analyzed with new diagnostic methods (microcalorimetry, PCR, alpha-defensin, etc.). Diagnostic speed and accuracy of these methods is compared to standard diagnostic methods in clinical routine, such as blood cultures of joint aspirates, cell count/differential, intra-operative tissue culture and histology and sonication.
Inclusion criteria: inclusion criteria:

 adult of 18 or more years

 written consent to participate in study

 suspicion of septic arthritis or periprosthetic joint infection

 joint aspirate minimum of 5 ml

Exclusion criteria: :

 is not able to understand the aim or purpose of this study

 empty joint aspirate

['Periprosthetic Joint Infection', 'Septic Arthritis']

Periprosthetic Joint Infection
Septic Arthritis


The Natural History of Gene Expression in the Lung Cells of Non-Smokers, Smokers and Ex-Smokers in Health and Disease

Summary: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD, commonly known as chronic bronchitis and emphysema). Despite this clear link, only 15-20% of smokers develop COPD suggesting that genetic factors affect the lung's susceptibility to the stress of cigarette smoke. The cells lining the airways (epithelium) and cells that help defend the lung (alveolar macrophages) of smokers develop gene expression changes that are different from that of nonsmokers. In the investigators' previous studies they have demonstrated that there are greater than 200 genes that are responsive to cigarette smoke in these cells. But the investigators do not know whether the gene expression is static or changes as a function of time. Genes that show significant changes over time may be relevant to the progression of the disease. Even though quitting smoking reduces the rate at which the lungs decline, many-smokers still go on to develop COPD. This study will provide insights into the natural history of smoking-related gene expression of the lung cells in health and disease.
Inclusion criteria: inclusion criteria:

 Group A: Healthy nonsmokers

 All study individuals should be enrolled in the Airway protocol #1204012331 Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies

 Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies

 Male and Female subject ≥18 years of age

 Never smokers is defined as someone who has smoked < 100 cigarettes per lifetime and whose urine nicotine <2 ng/mL and/or urine cotinine <5 ng/mL, at entry into the study

 Group B: Healthy current smokers Inclusion:

 All study individuals should be enrolled in the Airway protocol

 Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies

 Male and Female subject ≥18 years of age

 Active smoker as evidenced by self-report and urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL

 Group C: Healthy smokers who elect to stop smoking Inclusion:

 All study individuals should be enrolled in the Airway protocol

 Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies

 Male and Female subject ≥18 years of age

 Current smoker as evidenced by self-report and urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL

 Be a current smoker willing to stop smoking

 Group D - Current smokers with COPD Inclusion:

 All study subjects will be enrolled in the Airway protocol #1204012331 Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies

 All study subjects should meet the lung disease criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure

 All study subjects should be able to provide informed consent for the long term follow up study with repeated bronchoscopies

 Male and Female subject ≥18 years of age

 Active smokers as evidenced by urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL

 Group E - Current smokers with COPD who elect to stop smoking Inclusion:

 All study subjects will be enrolled in the Airway protocol #1204012331 Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies

 All study subjects should meet the lung disease criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure

 All study subjects should be able to provide informed consent for the long term follow up study with repeated bronchoscopies

 Male and Female subject ≥18 years of age

 Active smokers as evidenced by urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL

 Be a current smoker willing to stop smoking

Exclusion criteria: :

 Groups A - E

 Individuals unable to provide proper informed consent

 Habitual use of drugs and/or alcohol within the past six months (Acceptable: Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria)

 Individuals with asthma and with recurrent or recent (within three months) and/or acute pulmonary infection

 Individuals with allergy to lidocaine

 Significant kidney disease or subjects on dialysis

 Females who are pregnant or lactating or intending to become pregnant in the next 12 months

 Subjects who are HIV positive

 Subjects that have unstable coronary artery disease as evidenced by unstable angina, >Class II New York Heart Association (NYHA) cardiac status, history of congestive heart failure or MI within the last 12 months

 Subjects who are contraindicated for undergoing bronchoscopy

 Subjects having any medical condition that in the opinion of the investigator would preclude the subject from entering the study

 Groups D and E

 - Subjects may not have evidence of respiratory failure such as SpO2 <90% or PaO2 <60 mmHg

 Groups C and E

 Current major depression or other significant psychiatric disorder

 Subjects currently taking anti-depressant medication

['Chronic Obstructive Pulmonary Disease (COPD)', 'Smoking', 'Smoking Cessation', 'Chronic Bronchitis', 'Emphysema']


A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Lower Risk Myelodysplastic Syndrome (MDS) Without Del 5q

Summary: The purpose of this study is to investigate whether lenalidomide would reduce the number of red blood cell transfusions (RBC) needed in anemic (RBC transfusion-dependent) participants with low or intermediate-1 risk MDS without a deletion 5q chromosome abnormality. The study also investigated the safety of lenalidomide use in these participants. Two-thirds of the participants received oral lenalidomide and one-third of the participants received oral placebo.
Inclusion criteria: inclusion criteria:

 18 years or older

 Diagnosis of low or intermediate-1 risk Myelodysplastic (MDS) with any chromosome karyotype except del 5q[31]

 Anemia that requires red blood cell transfusions

 Resistant to erythropoiesis stimulating agents (ESAs) or blood erythropoietin level > 500 mU/mL

 Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2

 Must agree to follow pregnancy precautions as required by the protocol.

 Must agree to receive counseling related to teratogenic and other risks of lenalidomide

 Must agree not to donate blood or semen

 Must be willing to consent to two or more bone marrow aspirate procedures to be completed during study

Exclusion criteria: :

 Subjects previously receiving immunomodulating or immunosuppressive agents, or epigenetic or deoxyribonucleic acid (DNA) modulation agents

 Allergic reaction to thalidomide

 Renal insufficiency creatinine clearance (CrC1)<40 mL/min by Cockcroft-Gault method)

 Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 5 years. (Basal cell carcinoma of the skin, carcinoma in situ of the cervix, or stage Tumor (T) 1a or T1b prostate cancer is allowed)

 Absolute neutrophil count (ANC) < 500/uL

 Platelets < 50,000/uL

 Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3X upper limit of normal

 Uncontrolled hyperthyroidism or hypothyroidism

 Significant neuropathy

 Prior stem cell transplantation

 Anemia due to reasons other than MDS

 History of deep venous thrombosis (DVT) or pulmonary embolus (PE) within past 3 years

 Significant active cardiac disease within the past 6 months

 Known Human Immunodeficiency Virus (HIV) infection; known Hepatitis C infection or active Hepatitis B infection


Family Health and Development Project

Summary: The Family Health and Development Project (FHDP) is a randomized controlled trial to evaluate the effectiveness of the Intensive In-home Child and Adolescent Psychiatric Service (IICAPS) intervention, targeting emotionally, behaviorally, and/or psychiatrically disordered children at risk of a psychiatric inpatient admission and their families. Children and families are randomized to receive IICAPS or Home-based Child Treatment Coordination (Home-based CTC), a home-based case management intervention for coordination of mental health services for children. Approximately 144 children and their families will be enrolled for a 12 month study period. Data will be collected through interviews with the child's parent/legal guardian, and from the child's teacher, the child's school, and the Department of Social Services (claims data). This study will test the hypotheses that children receiving IICAPS will be less likely to exhibit out-of-control behaviors and less likely to experience a psychiatric hospitalization and/or out-of-home placement during and up to six months post-discharge from services.
Inclusion criteria: inclusion criteria:

 child has a Diagnostic and Statistical Manual-IV (DSM-IV) diagnosis

 child at risk of psychiatric hospitalization due to serious out-of-control behaviors

 child resides in home of legal guardian, who is primary caregiver

 child insured by Medicaid

 score in the borderline clinical or clinical range on the Externalizing Scale of the Child Behavior Checklist (CBCL)

Exclusion criteria: :

 referred to IICAPS by a probation officer

 suffers from an unstable, chronic medical comorbidity

 prior receipt of IICAPS

['Intensive In-home Child and Adolescent Psychiatric Service', 'Home-based Child Treatment Coordination']


Examining New Diagnostic Tests for Acute Kidney Injury After Heart Surgery

Summary: People who undergo coronary artery bypass grafting (CABG) or heart valve surgery may experience acute kidney injury (AKI) after their surgery. Current medical tests cannot identify AKI until approximately 48 hours after it occurs. This study will examine three new biomarkers in blood and urine that may provide a more effective and faster way of predicting AKI in people who undergo CABG or heart valve surgery.
Inclusion criteria: inclusion criteria for Adults: (must have at least one of the following)

 Emergent surgery

 Pre-existing kidney impairment (baseline serum creatinine greater than 2 mg/dL)

 Ejection fraction less than 35%

 At least 70 years old

 Diabetes mellitus

 Combined CABG and valve surgery

 Repeat CABG or valve surgery

Exclusion criteria:  for Adults:

 Pre-operative acute kidney injury

 Enrolled in a conflicting research study

 Prior kidney transplantation

 Baseline serum creatinine level greater than 4.5 mg/dL

 Nephrotoxic drugs administered pre-operatively

 Surgery for only left ventricular assist device

 inclusion criteria for Children:

 Undergoing open heart surgery

['Kidney Failure, Acute', 'Renal Insufficiency']

Kidney Failure
Acute
Renal Insufficiency


Evaluation of the Kinetic Properties of an Autologous Microbiome Transplant in Adult Atopic Dermatitis Patients

Summary: Unlike healthy control skin, the skin of patients with atopic dermatitis (AD) is frequently colonized by Staphylococcus aureus (S. aureus), putting these patients at increased risk of S. aureus skin infections. In addition, research in the investigator's lab has shown that these patients have fewer protective Staphylococcal species such as Staphylococcus epidermidis (S. epidermidis) that are known to produce antimicrobial peptides that play a role in protecting the skin from invading pathogens. In this study, the study team will attempt to decrease S. aureus colonization and increase colonization by protective Staph species in AD patients by first culturing the bacteria on subjects' lesional AD skin. The study team will selectively grow the subject's protective Staph colonies and place them into a moisturizer. The first part of the study will determine the half-life of the bacteria-containing moisturizer. The bacteria-containing moisturizer will be applied to a subject's arm, and the subject will return at four different time points over the next three days for skin swabs of the arm that will be used to determine the amount and type of bacteria on the arm at those time points. In the second part of the study, the subject will apply moisturizer containing his own antimicrobial bacteria to one of his arms for a total of 6 times at a frequency determined by the half-life, which will be computed at the end of the first part of this experiment. The subject will return prior to the 7th application time point for skin swabs of the arm to ensure that there are still viable bacteria from the moisturizer present on the arm. In the third part of the study, each subject will receive both moisturizer as well as moisturizer plus his own antimicrobial bacteria. The subject will apply the moisturizer to one arm and the moisturizer plus bacteria to the other arm daily for a total of 15 days. Subjects will return to the clinic every 5 days for skin swabs and clinical evaluations. If the moisturizer containing bacteria is able to decrease the S. aureus colonization on subject's arms, the study team hypothesizes that subjects will have improvement of their AD symptoms.
Inclusion criteria: inclusion criteria:

 Male or female subjects who are not pregnant or lactating

 18-80 years of age

 Diagnosis of atopic dermatitis for at least 6 months using the Hanifin and Rajka Diagnostic Criteria for atopic dermatitis

 Presence of lesional atopic dermatitis skin in both antecubital fossae

 Positive S. aureus colonization based on results of a skin culture taken from one of their AD-affected antecubital fossae during the screening visit

Exclusion criteria: :

 Use of any topical AD treatments (including topical steroids, topical calcineurin inhibitors) to either arm within one week of either screening visit

 Use of any oral/systemic AD therapies (antihistamines, steroids) within 28 days of either screening visit

 Severe AD that would worsen significantly from holding a participant's usual topical/oral AD medications for the time periods required in the inclusion/

Moisturizer with each subject's own antimicrobial bacteria


Dynamic Carbon Dioxide (CO2) Administration for Sleep Apnoea

Summary: Normally breathing is controlled by a reflex that responds to the levels of carbon dioxide (CO2) in the blood. In heart failure, where the heart muscle is damaged and therefore does not pump as well, this reflex is exaggerated. The result is a vicious circle: blood CO2 levels fluctuate wildly and as a result breathing also fluctuates with patients hyperventilating at times and briefly stopping breathing at others. During sleep this is called central sleep apnoea (CSA).~Patients with CSA wake up throughout the night and whilst some patients are oblivious to this, others are consciously breathless and many patients are tired during the day and feel unable to perform their daily activities.~As part of the body's stress response to the erratic pattern of breathing, both blood pressure and heart rate may rise to a level that is harmful in a failing heart, exacerbating the underlying heart failure. Indeed patients who demonstrate this CSA die sooner than those who have heart failure and stable breathing.~There are no proven specific therapies for CSA that stabilise breathing, improve sleep quality, and prolong life. We have designed a system which delivers very small doses of CO2, when the blood level of CO2 is predicted to be low. During short daytime recordings, using this system, we have demonstrated that it is possible to stabilise the body's CO2 levels.~We aim to test what happens when CO2 is given overnight whilst the patient is sleeping to see whether we can stabilise their breathing over longer durations and whether sleep quality could be improved so that patients are less tired during the day. In addition, we would like to measure whether the stress response is lessened if the breathing is successfully stabilised.
Inclusion criteria: inclusion criteria:

 Men and women 18 to 79 years of age who have New York Heart Association (NYHA) functional class I through IV heart failure due to ischemic, hypertensive, or idiopathic dilated cardiomyopathy and whose condition had been stabilized by means of optimal medical therapy for at least one month;

 An LVEF of less than 40% and central sleep apnea, defined as 15 or more episodes of apnea and hypopnea per hour of sleep, more than 50 percent of which are determined to be central rather than obstructive.

Exclusion criteria: :

 Pregnancy,

 Myocardial infarction,

 Unstable angina or cardiac surgery within the previous three months.


Surgical Indirect Revascularization For Symptomatic Intracranial Arterial Stenosis

Summary: Stroke due to intracranial arterial atherosclerosis is a significant medical problem, carrying one of the highest rates of recurrent stroke despite best medical therapy, with annual recurrence rates as elevated as 25% in high risk groups.~The goal of this investigation is to advance a promising surgical treatment for symptomatic atherosclerotic intracranial stenosis - encephaloduroarteriosynangiosis (EDAS). The investigation will test in a phase II futility trial the potential of EDAS for further development before proceeding with the design of a definitive clinical trial of EDAS Revascularization in patients with Symptomatic Intracranial Arterial Stenosis (ERSIAS).~The investigation is a 4-year futility trial to test the hypothesis that EDAS revascularization combined with aggressive medical therapy warrants further evaluation in a subsequent pivotal trial as an alternative to aggressive medical management alone for preventing the primary endpoint of stroke or death in patients with symptomatic intracranial arterial stenosis (Specific Aim 1). During the investigation the time course of collateralogenesis and perfusion improvement following EDAS will also be evaluated (Specific Aim 2.
Inclusion criteria: inclusion criteria:

 TIA or non-severe stroke within 30 days of enrollment attributed to 70% to 99% stenosis* of a major intracranial artery (carotid artery or MCA)

 *May be diagnosed by TCD, MRA, or CTA to qualify, but must be confirmed by catheter angiography as per usual clinical practice.

 Modified Rankin scale score of ≤3

 Target area of stenosis in an intracranial artery that has a normal diameter of 2.00 mm to 4.50 mm

 Target area of stenosis is ≤14 mm in length

 Age ≥30 years and ≤80 years

 * Patients 30 to 49 years of age are required to meet at least 1 additional criteria (i-vi) provided below to qualify for the study. This additional requirement is to increase the likelihood that the symptomatic intracranial stenosis in patients 30 to 49 years is atherosclerotic: i. Insulin-dependent diabetes for at least 15 years ii. At least 2 of the following atherosclerotic risk factors: hypertension (BP ≥ 140/90 mm Hg or on antihypertensive therapy); dyslipidemia (LDL ≥130 mg/dL or HDL ≤40 mg/dL or fasting triglycerides ≥150 mg/dL or on lipid lowering therapy); smoking; non-insulin-dependent diabetes or insulin-dependent diabetes of <15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, and peripheral vascular surgery in parent or sibling who was < 55 years of age for men or < 65 for women at the time of the event.

 iii. History of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease iv. Any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by noninvasive vascular imaging or catheter angiography and is considered atherosclerotic v. Aortic arch atheroma documented by noninvasive vascular imaging or catheter angiography vi. Any aortic aneurysm documented by noninvasive vascular imaging or catheter angiography that is considered atherosclerotic

 Negative pregnancy test in a female who has had any menses in the last 18 months

 Patient is willing and able to return for all follow-up visits required by the protocol.

 Patient is available by phone.

 Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent.

 Demonstration of poor or no collateral flow in the territory of the qualifying stenotic vessel (ASITN/SIR Collateral Flow Grades 0-2) and hypoperfusion of the vascular territory in MRI.

Exclusion criteria: :

 Tandem extracranial or intracranial stenosis (70-99%) or occlusion that is proximal or distal to the target intracranial lesion

 Bilateral intracranial vertebral artery stenosis of 70% to 99% and uncertainty about which artery is symptomatic (e.g., if patient has pontine, midbrain, or temporal occipital symptoms)

 Stenting, angioplasty, or endarterectomy of an extracranial (carotid or vertebral artery) or intracranial artery within 30 days before the expected enrollment date

 Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform staged angioplasty followed by stenting of target lesion

 Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to an intracranial stenosis

 Presence of intraluminal thrombus proximal to or at the target lesion

 Any aneurysm proximal to or distal to the stenotic intracranial artery

 Intracranial tumor (including meningioma) or any intracranial vascular malformation

 Computed tomographic or angiographic evidence of severe calcification at target lesion

 Thrombolytic therapy within 24 hours before enrollment

 Progressive neurologic signs within 24 hours before enrollment

 Brain infarct within previous 30 days of enrollment that is of sufficient size (> 5 cm) to be at risk of hemorrhagic conversion during or after surgery

 Any hemorrhagic infarct within 14 days before enrollment

 Any hemorrhagic infarct within 15 to 30 days that is associated with mass effect

 Any history of a primary intracerebral (parenchymal) hemorrhage

 Any other intracranial hemorrhage (subarachnoid, subdural, or epidural) within 30 days

 Any untreated chronic subdural hematoma >5 mm in thickness

 Intracranial arterial stenosis related to arterial dissection, Moya-Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebrospinal fluid pleocytosis; radiation-induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process, and suspected recanalized embolus

 Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction <30%

 Known allergy or contraindication to aspirin and local or general anesthesia

 History of life-threatening allergy to contrast dye. If not life-threatening and can be effectively pretreated, patient can be enrolled at physician's discretion

 Known absolute contraindication to obtaining MRI studies, such as magnetically activated implanted devices (cardiac pacemakers, insulin pumps, neuro-stimulators, and cochlear implants), MRI incompatible orthopedic implants, and free metallic fragments in the brain or eye.

 Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets <100,000, hematocrit <30, INR >1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic BP>180 mm Hg or diastolic BP>115 mm Hg), severe liver impairment (AST or ALT > 3 times normal, cirrhosis), creatinine > 3.0 (unless on dialysis)

 Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 90 days after enrollment

 Indication for warfarin or heparin beyond enrollment (NOTE: Exceptions allowed for use of subcutaneous heparin for deep venous thrombosis prophylaxis while hospitalized)

 Severe neurologic deficit that renders the patient incapable of living independently

 Dementia or psychiatric problem that prevents the patient from following an outpatient program reliably

 Comorbid conditions that may limit survival to < 3 years

 Females who are pregnant or of childbearing potential and unwilling to use contraception for the duration of this study

 Enrollment in another study that would conflict with the current study

 Surgical Specific

['Intracranial Arterial Stenosis', 'Intracranial Atherosclerosis', 'Ischemic Stroke', 'Cerebral Angiogenesis']

Intracranial Arterial Stenosis
Intracranial Atherosclerosis
Ischemic Stroke
Cerebral Angiogenesis


Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD

Summary: In selected patients with acute pulmonary embolism(PE), low dose (50mg/2h) recombinant tissue plasminogen activator (rt-PA) regimen had been reported to have less bleeding tendency than the FDA-approved rt-PA 100mg/2h regimen 100mg/2h regimen (3% vs.10%), it is worthwhile to reveal whether low dose rt-PA plus low molecular weight heparin (LMWH) can rapidly reverses RV pressure overload in PE, but not increase bleeding and other adverse events. The aim of the study is to compare thrombolytic treatment with LMWH in patients with acute normotensive PE with right ventricular dysfunction(RVD).
Inclusion criteria: inclusion criteria:

 18 y≤Age≤75y

 Acute PE (first symptoms occurred 14 d or less before randomization) confirmed by lung scan, or a positive computed tomographic pulmonary angiogram, or a positive selective pulmonary angiogram

 Hemodynamic stability, diastolic pressure>90mmHg.

 RV dysfunction confirmed by echocardiography (≥1 criterion), except left-side heart disease, congenital heart disease and mitral valve disease.

 Increase of the right ventricle showed presented with RV end-diastolic anteroposterior diameter >25 mm, Right/left ventricular end-diastolic diameter >1 (apical or subcostal 4-chamber view) or Right/left ventricular end-diastolic anteroposterior diameter >0.5

 Hypokinesis of RV-free wall (range of motion less than 5 mm)

 Tricuspid regurgitation pressure >30mmHg

Exclusion criteria: :

 RV anterior wall thickness > 5mm confirmed by echocardiography

 Active internal bleeding and spontaneous intracranial hemorrhage in preceding 6 months

 Major surgery, organ biopsy or non-compressible punctures within 2 weeks

 Ischemic stroke occurred within 2 months

 Gastrointestinal bleeding within 10 days

 Severe trauma occurred within15 days

 Neurosurgery or eye surgery within 1 months

 Severe hypertension difficult to control (systolic blood pressure>180mmHg or diastolic blood pressure>110mmHg)

 Cardiopulmonary resuscitation

 Platelet count less than 100×109 / L

 Pregnancy, or within 2 week post partum

 Infective endocarditis; left atrial thrombus; aneurysm

 Serious liver and kidney dysfunction

 Diabetic hemorrhagic retinopathy

 Suffering with bleeding disorders

 Chronic thromboembolic pulmonary hypertension

 Moderate to severe chronic obstructive pulmonary disease (COPD).

['Recombinant tissue plasminogen activator (rt-PA)', 'Low Molecular Weight Heparin']

['Pulmonary Thromboembolisms', 'Pulmonary Embolism']

Pulmonary Thromboembolisms
Pulmonary Embolism


Effectiveness of LNS and MNP Supplements to Prevent Malnutrition in Women and Their Children in Bangladesh

Summary: The program effectiveness study aims to assess the effect of a lipid-based nutrition supplement (LNS) and micronutrient powder (MNP) provided in a programmatic context for improving maternal nutritional status during pregnancy and lactation (LNS only), and preventing malnutrition in infants and young children (LNS and MNP) in Bangladesh.
Inclusion criteria: inclusion criteria:

 Gestational age ≤ 20 weeks

 Planning to remain in the study area during pregnancy and the following three years (i.e., a permanent resident of the study area)

Exclusion criteria: :

 Pregnancy identified and registered in the CHDP program before the beginning of the enrollment.


Low Dose Prolonged Infusion of Tissue Type Plasminogen Activator Therapy in Massive Pulmonary Embolism

Summary: The aim of the present study was to assess the effects of low-dose (25mg) prolonged administration (in 6 hours) of tissue type plasminogen activator (tPA) on in-hospital mortality and outcomes in patients with massive PE.
Inclusion criteria: inclusion criteria:

 Patients with massive PE aged 18 years or older with confirmed PE and able to give informed consent will be included in the study. PE is defined according to current guidelines as adult patients presenting with signs and symptoms suggestive of PE plus imaging documentation on computed tomography angiography. Massive PE was defined as acute PE with sustained hypotension (systolic blood pressure<90 mm Hg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular [LV] dysfunction), pulselessness, or persistent profound bradycardia (heart rate<40 bpm with signs or symptoms of shock).

Exclusion criteria: :

 Patients with prior intracranial hemorrhage, known structural intracranial cerebrovascular disease (eg, arteriovenous malformation), known malignant intracranial neoplasm, ischemic stroke within 3 months, suspected aortic dissection, active bleeding or bleeding diathesis, recent surgery encroaching on the spinal canal or brain, and recent significant closed-head or facial trauma with radiographic evidence of bony fracture or brain injury were excluded from the study.

['25 mg Actilyse ( Boehringer Ingelheim, Germany) infusion in 6 hours']

25 mg Actilyse ( Boehringer Ingelheim
Germany) infusion in 6 hours


Cigarette Smoking and Oral Microbiota

Summary: Background:~- Normal bacteria and other tiny organisms (the microbiota) live in the mouth and nose. They contribute to human health in many ways, including digesting food and balancing hormones. Testing samples from the mouth can show how microbiotas are related to health and disease. However, the microbiota in a person's mouth differs depending on the methods of collection and the part of the mouth that is tested. Understanding what can change the microbiota (including mouth sites, and what a person eats or smokes) will give more information on how to study oral microbiota and smoking-related cancers and other diseases.~Objectives:~To see how smoking affects the microbiotas in mouth and nose.~To determine which collection method for mouth specimens should be used for studying microbiota.~Eligibility:~Individuals at least 18 years of age who have been using tobacco products regularly for at least 5 years.~Individuals at least 18 years of age who have never smoked.~Design:~Participants will be screened with a physical exam and medical history.~Participants will have a dental exam. They will provide a saliva sample. The dentist will take swabs from the inside of the mouth, including the tongue, tonsils, gums, and teeth. The inside of the nose will also be swabbed.~Participants will also fill out a questionnaire. It will ask about their history of smoking and consumption of alcohol, tea, and coffee. It will also ask about current medications, including antibiotics.
Inclusion criteria: inclusion criteria

 This study will recruit a convenience sample of 50 volunteers (25 current smokers with at least 5 years of smoking history, 25 never smokers). Current smokers are defined as individuals who have smoked more than 100 cigarettes in their lifetime and have smoked 5 or more cigarettes in the last 24 hours. Recent use of other tobacco products (pipe, cigar, snuff, cigarillos, and chewing tobacco) is an overall exclusion, but use in the remote past (> 6 month ago) is acceptable in smokers. Never smokers are defined as individuals who have never smoked cigarettes nor used any other tobacco products including pipe, cigar, snuff, cigarillos, or chewing tobacco.

 The ethnic mix of the clinic is roughly 50% Caucasians and 50% African- Americans with a small number of unspecified or other racial groups. The median age is about 50 and the gender mix consists of an equal number of men and women. We therefore will select smokers and frequency match to non-smokers based on ethnicity (White, African-American), gender (male, female), and age (above or below the median, estimated to be 50).

Exclusion criteria:

 We will exclude pregnant women and other racial groups because they may represent very small numbers and thus be difficult to match. Hormonal changes associated with pregnancy and unique cultural habits associated with specific ethnic groups could be associated with highly unique or variable microbiome patterns, and therefore reduce the power to detect differences associated with smoking which is our primary goal. We will also exclude subjects with antibiotic usage in the last three months and subjects with previous diagnosed major periodontal disease or cancer because they might be potential confounders.

['Microbiota', 'Lung Cancer', 'Oral Cancer']


Individualized Fortification of Breast Milk

Summary: The proposed research will investigate individualized fortification of breast milk based on daily milk analysis of carbohydrate, protein, and fat content in a randomized double blind controlled trial. The combination of additional fat, carbohydrate and protein and commercial fortifier will be added to ensure that the milk contains the target amounts of nutrient. Growth and development of these infants will be compared with that of infants fed mother's milk that has been supplemented with the current standard amounts. The postnatal growth of the infants will be assessed by measuring weight, length and head circumference and fat and lean mass using highly accurate, non-invasive methods throughout the intervention period and at the first follow-up visit after discharge at 3 months. Neurological development will be analyzed at the age of 18 months.~The investigators hypothesize that individualized fortification of breast milk improves the nutritional intake of preterm infants, optimizing growth, and thus this will positively impact neurodevelopment and health.
Inclusion criteria: inclusion criteria:

 Gestational age < 32weeks (maternal dates or early fetal ultrasound);

 Tolerating an enteral intake of ≥ 100 ml/kg/d for ≥ 24h;

 Subject is anticipated to receive the intervention for ≥ 3 consecutive weeks after full enteral feeding (≥ 150 mL/kg/d) has been achieved; and

 Written informed consent has been obtained from the infant's legal representative.

Exclusion criteria: :

 Infants with intrauterine growth restriction, small for gestational age defined by a weight less than 3rd percentile using sex specific reference data for birth weight

 Gastrointestinal malformation, major congenital anomalies and chromosomal abnormalities;

 Babies with enterostoma or short gut syndrome;

 Necrotizing enterocolitis, defined by feeding intolerance associated with positive x-ray findings (pneumatosis intestinalis - Bell Stage 2; air in the biliary tract or free air in the peritoneum - Bell Stage 3);

 Renal disease, defined by symptoms (oliguria, anuria, proteinuria, hematuria) associated with an increased blood urea nitrogen 10 mmol/L79 and creatinine of 130 mmol/L80;

 Hepatic dysfunction, defined by jaundice (direct bilirubin >1.0 mg/dl) that is associated with one or more abnormal liver function tests (AST, ALT or GGT);

 Participation in another clinical trial that may affect outcomes of this study; or

 Probability of transfer to another NICU or level II nursery outside the McMaster Children's Hospital before the minimum period of three weeks is completed.

 Post-randomisation

['Individualized fortification of breast milk', 'Routine fortification of breast milk']

['Postnatal Growth Disorder', 'Neurodevelopment']

Postnatal Growth Disorder
Neurodevelopment


Wound Healing After Emergency Appendicectomy

Summary: The purpose of this trial is to compare two techniques of wound closure in open appendicectomies in adult patients: continuous, absorbable, intradermal suture and interrupted, non-absorbable sutures.
Inclusion criteria: inclusion criteria:

 Adult patient with acute appendicitis

Exclusion criteria: :

 Children


Intravenous Proton Pump Inhibitor for Peptic Ulcer Bleeding

Summary: A large dose of PPI is effective in preventing peptic ulcer rebleeding. The investigators hypothesize that 40 mg/q6h pantoloc is equivalent to 8mg/h pantoloc in preventing rebleeding.
Inclusion criteria: inclusion criteria:

 Patients were accepted for endoscopic therapy if a peptic ulcer with active bleeding, a non-bleeding visible vessel (NBVV) or an adherent blood clot at the ulcer base was observed within 24 hours of hospital admission.

Exclusion criteria: :

 If patients were pregnant

 Did not obtain initial hemostasis with endoscopic injection of epinephrine

 Did not give written informed consent

 Had bleeding tendency (platelet count < 50×109/L, serum prothrombin < 30% of normal, or were taking anticoagulants), uremia.


The Flamenco (Fitness League Against MENopause COsts) Project

Summary: Spain is the second country in the world that consume more drugs. The average drug expenditure per capita in Andalucía during 2011 was 219.2 €. This drug spending increases during the perimenopausal period. According to the Study of the Economic Impact of Sport on Health Spending of the Ministry of Health of the Generalitat of Catalonia, for every euro invested in sports promotion 50 euros are saved in health spending accumulated over 15 years. The main objectives of this project are: i) To analyze the (cost-effectiveness) effect of an exercise program on the prescription of drugs in a sample of Andalusian women aged 45-60 years. ii ) To study the level of physical activity and sedentarism (measured objectively by accelerometry ) , functional capacity , quality of life and clinical profile of this population. iii ) To analyze the relationship between levels of physical activity / sedentarism and pharmaceutical expenditure. In the present project, an exercise program aimed at minimizing symptoms and health problems associated with the perimenopausal period will be performed (Dyslipidemia, diabetes, anxiety, depression, quality of life, quality of sleep, obesity, osteoporosis and cardiovascular disease). A total of 160 perimenopausal women will be randomly assigned to the intervention group exercise (n = 80 ) or to the usual care group (n = 80). Participants in the intervention group will train 3 days / week ( 60 min per session ) for 16 weeks.~With the analysis of the results of this project new patterns of objective work as well as the most significant practical resources for the design of a master plan may be determined. Results are expected to be able to shed some light on the implementation of programs of health promotion that are both time beneficial for the Andalusian Public Health and for the family , institutional and community economy.
Inclusion criteria: inclusion criteria:

 Age: 45-60 years.

 Not to have other severe somatic or psychiatric disorders, or other diseases that prevent physical loading (Answer no to all questions on the Physical Activity Readiness Questionnaire-PAR-Q) .

 Not to be engaged in regular physical activity >20 min on >3 days/week.

 Able to ambulate, with or without assistance.

 Able to communicate.

 Informed consent: Must be capable and willing to provide consent.

Exclusion criteria: :

 Acute or terminal illness.

 Myocardial infarction in the past 3 months.

 Not capable to ambulate.

 Unstable cardiovascular disease or other medical condition.

 Upper or lower extremity fracture in the past 3 months.

 Severe dementia (MMSE < 10).

 Unwillingness to either complete the study requirements or to be randomised into control or training group.

 Presence of neuromuscular disease or drugs affecting neuromuscular function.

['Quality of Life', 'Cardiovascular Diseases', 'Diabetes', 'Dyslipidemias', 'Metabolic Syndrome']

Quality of Life
Cardiovascular Diseases
Diabetes
Dyslipidemias
Metabolic Syndrome


OnabotulinumtoxinA as Treatment for Major Depressive Disorder in Adult Females

Summary: This study will evaluate the safety and efficacy of onabotulinumtoxinA (BOTOX®) compared with placebo as treatment for major depressive disorder (MDD) in adult females.
Inclusion criteria: inclusion criteria:

 Moderate to severe major depressive disorder

Exclusion criteria: :

 Prior treatment with botulinum toxin of any serotype for any reason

 Use of antidepressant medication for depression within 2 weeks of study

 Diagnosis of Myasthenia gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis


An Investigation Into the Mechanism of Inhalation Cough Challenge

Summary: Despite its commonplace use in respiratory medicine the mechanism whereby inhalation challenge with a variety of mild acid aerosols produces a dose related and predictable cough is unknown. In this proposal the investigators wish to use established cough challenge methodology to explore the mechanism of action of agents provoking cough both in health and disease.~The hypotheses to be tested include:~Intracellular changes in pH, rather than extracellular changes, are key in the activation of TRP receptors, the main sensor for provoking cough.~ATP acting through P2X channels is the mechanism of increased nerve excitability underlying cough hypersensitivity.
Inclusion criteria: inclusion criteria:

 Patients will be required to demonstrate significant cough symptoms by a score greater than 20/70 on the Hull Airways Reflux Questionnaire.

 All patients must be current non-smokers.

 Patients must be on stable medication for at least one month.

 Patients must be able to attend the trials unit on at least 3 occasions.

 Patients must have normal lung function patients must be able to give informed consent

Exclusion criteria: :

 Subjects who are pregnant, or have pacemakers in situ are excluded from this study.

 Those with a serious comorbid conditions such as cancer, severe COPD, or heart failure will be excluded.

 Those who are non-English speakers and special groups (i.e. mentally ill, children under 16 years of age, and those suffering from dementia) will be excluded.

 No test will be performed on any subject during an acute worsening of asthma or upper airway infection. If the subject has had an upper airway infection in the last three weeks they will be offered another appointment.

 If the subject has taken any over the counter (OTC) cough mixture within the last twelve hours: If the subject is willing to come back another time for challenge testing, another appointment should be made.

 If the subject has had any food or drink products containing caffeine or menthol within the last hour. If the subject is unwilling to wait for 1 hour before starting the test, the subject should return another time. If the subject is unwilling to return another time, testing should proceed and the medication used recorded.

 If the participant is currently involved in research, or within 3 months of participation in any type of research, they will be excluded from this study.

['Nebulised citric acid in serial dilutions', 'Nebulised ATP solution in serial dilutions', 'Nebulised TRPA1 agonist solution in serial dilutions']


Acute Effect of Aclidinium on Hyperinflation and Ventilation Inhomogeneity in Severe COPD Patients

Summary: Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung hyperinflation and flow limitation. These physiopathological modifications are secondary to loss of elastic recoil and bronchial obstruction due to emphysema.~The cornerstone of COPD treatment is represented by inhaled beta-2 agonists and anticholinergics. The molecules of the latter classes can be characterized by short lasting action (few hours), long acting action (12 hours) or ultra long acting duration of action (24 hours).~For years the only anticholinergic (or antimuscarinic) drug other than those used by aerosol, was Tiotropium Bromide. Recently two new antimuscarinic agents have been launched on the market: glycopyrronium bromide (once daily) and aclidinium (twice daily).~The Single Breath Nitrogen Test is capable of identifying the pulmonary closing volume. The part of the curve that reflects lung ventilation inhomogeneity is the slope of phase III~For COPD patients, the most important characteristic for an inhalatory drug is a prompt action in order to give a quick relief from respiratory symptoms, in particular dyspnoea.~The objective of this study is to study the acute action of glycopyrronium and aclidinium in terms of reduction of hyperinflation, pulmonary specific resistances, lung volume distribution and dyspnoea at rest in severe COPD patients.~To our knowledge no study has explored these aspects before.
Inclusion criteria: inclusion criteria:

 Signature of informed consent

 COPD patients with age raging from 50 to 85 years old

 Patients with at least a history of COPD of one year

 COPD patients clinically stable in the last three months

 COPD subjects with Forced Expiratory Volume at one second (FEV1)<50% of predicted value

 COPD subjects with Residual Volume (RV) >125% predicted value

 FEV1/Forced Vital Capacity (FVC) <88% (males) or <89% (females) of Low Levels of Normality (LLN)

 COPD former or active smokers with at least a smoking history of 20 pack year

Exclusion criteria: :

 Acute Bronchial Exacerbation at recruitment

 Fertile women with age between 18 and 50 years old or with active period

 Pregnancy

 Subjects enrolled in other clinical trials or that have taken part in one of them in the month preceding the enrollment.

 FEV1/FVC more than 70% of predicted value in basal conditions

 FEV1 more than 70% of predicted value in basal conditions

 Known deficit of alpha 1 antitrypsin

 Subjects that underwent a Lung Volume Reduction Surgery (LVRS)

 Subjects with known positivity to Human Immunodeficiency Virus (HIV)

 Misuse of alcool or drugs

 Lack of compliance in performing respiratory tests

 Subjects not capable to follow the study prescriptions because of psychic disorders or language problems.

 Long Term Oxygen Therapy with flows > 6 litres per minute (l/min) at rest

['Aclidinium Bromide', 'Glycopyrronium Bromide']

Aclidinium Bromide
Glycopyrronium Bromide

['Chronic Obstructive Pulmonary Disease']


BOAT: Beta Blocker Uptitration With OptiVol After Cardiac Resynchronization Therapy (CRT)

Summary: Many heart failure patients are unable to reach target beta blocker doses. This study will address whether cardiac resynchronization therapy (CRT) will enable uptitration of beta-blockers to target doses and whether it will favorably affect remodeling by reducing left ventricular end systolic volume (LVESV), with measurable clinical benefit, beyond CRT alone (without changes in beta-blocker dose).
Inclusion criteria: inclusion criteria:

 NYHA III-IV

 QRS > 120 msec

 On medical therapy, but beta blocker dose not @ target (carvedilol 25 bid, metoprolol succinate 200 qd)

Exclusion criteria: :

 QRS < 120 msec

 On target beta blocker dose

['Beta blocker (carvedilol or metoprolol succinate)', 'CRT (cardiac resynchronization therapy)']


New Approaches to Improve Coverage and Compliance of Antimalarial Treatment for Pregnant Women in Rural Africa

Summary: Malaria in pregnancy contributes substantially to maternal anaemia and low birth weight: effective malaria control in pregnancy could avoid about 10,000 maternal and up to 200,000 infant deaths every year. Intermittent preventive treatment with the drug sulfadoxine-pyrimethamine (IPTp-SP), administered at least twice during routine antenatal clinics, is recommended by the World Health Organization for areas of moderate to high malaria transmission, including Sub-Saharan Africa.~Studies carried out in Kenya and Malawi before 2004 had showed that two doses of IPTp-SP significantly reduce maternal anaemia, placental malaria parasitaemia and low birth weight. However, in countries where this strategy had been introduced as part of national policy, the coverage of the target population has varied widely, with estimates of 33-93% for uptake of one dose and 24-68% for two doses, and no country had reached the goal of 80% of pregnant women receiving at least 2 doses of IPTp. New approaches designed to improve IPTp coverage were therefore urgently needed.~This study was therefore set up in 2002, in order to evaluate the additional effect of a targeted promotional campaign on antenatal clinics utilization and on coverage and uptake of Intermittent preventive treatment with sulfadoxine-pyrimethamine in a rural health district in Burkina Faso; and to investigate the effectiveness of intermittent preventive treatment with the sulfadoxine-pyrimethamine compared with weekly chloroquine, in order to provide additional evidence to the Burkinabé Ministry of Health for an impending policy change.
Inclusion criteria: inclusion criteria:

 Female

 First or second trimester of pregnancy

 First or second pregnancy

 Resident in the study area

Exclusion criteria: :

 - Refuse to give informed consent


Functional Outcome After Incisional Hernia Repair: Open Versus Laparoscopic Repair

Summary: Background: Midline incisional hernia is reported from 0,5 to 11% after abdominal operations. Primary repair without mesh reinforcement is almost abandoned because of high recurrence rates (24 to 46%). Use of prosthetic mesh in incisional hernia repair lowered the recurrence rates under 10%. Recurrence rate alone is not the main quality criterion for incisional hernia repair anymore. Large series and meta-analyses confirmed the value of laparoscopic repair as at least equal if not better compared with open repair. Discomfort, pain, diminished quality of life and body image alteration influences functional well being. No baseline information exists in any of these fields treating pre- or post-operative phases in patients with incisional hernia. Respiratory functions and medico-economic evaluation are other rarely investigated fields that we consider in our trial. The objective of this study is to analyse the functional outcome status of patients after laparoscopic incisional hernia repair compared to open repair.~Methods: A randomized controlled non-blinded clinical trial is designed to compare laparoscopic incisional hernia mesh repair with open repair on post operative pain, health related quality of life outcomes, body image and cosmetic measurements, respiratory functions, recurrence rates, and cost. Volunteers will be recruited in Geneva University Hospital, department of surgery, visceral surgery unit. Eligibility criteria is male patient aged over 18 years, with reducible incisional hernia who are candidates for elective surgery and medically fit for general anesthesia.30 patients will be enrolled for each group. Follow-up will take place at 10th, 30th days as well as 3 12 and 24 post operative months by questionnaires and by clinical exam by independent expert. An overall cost-analysis will be realized. Patient enrollment in the study will start in April 2008 and estimated to end in september 2009.
Inclusion criteria: inclusion criteria:

 Informed consent

 Age 18 years or older

 Diagnosis of reducible incisional hernias up to 200 cm²

 Medically fit for general anesthesia

 Comprehension and use of French language

 Installed in the geographical region without foreseeable move for two years

Exclusion criteria: :

 Incarcerated hernia

 Ongoing chronic pain syndrome, other than hernia origin

 Coagulation disorders, prophylactic or therapeutic anticoagulation, unable to stop platelet antiaggregation therapy 10 days before surgery

 American Society of Anesthesiology Class 4 and 5 patients

 Emergency surgery, peritonitis, bowel obstruction, strangulation, perforation

 Mentally ill patients

 Presence of local or systemic infection

 Life expectancy < 2 years

 Any cognitive impairment (Psychiatric disorder, Alzheimer's disease etc.)

 Morbid obesity (BMI over 40)

['Laparoscopic repair', 'Open midline incisional hernia repair']

Laparoscopic repair
Open midline incisional hernia repair

['Hernia, Ventral', 'Body Image', 'Respiratory Function Tests', 'Quality of Life', 'Laparoscopy']

Hernia
Ventral
Body Image
Respiratory Function Tests
Quality of Life
Laparoscopy


Safety Study of FSME-IMMUN NEW in Healthy Children and Adolescents Aged 1 to 15 Years

Summary: The purpose of this study is to investigate the safety of five consecutive lots of FSME-IMMUN NEW in healthy volunteers. The main criterion for investigation is the fever rate after the first vaccination in three different age classes. The immunogenicity of 0.25 ml FSME-IMMUN NEW has been demonstrated in previous clinical studies in children; therefore, in the present study, immunogenicity was investigated in a subgroup only.
Inclusion criteria: inclusion criteria:

 Male and female children and adolescents will be eligible for participation in this study if:

 they are aged 1 year (from the 1st birthday) to < 16 years (to the last day before the 16th birthday);

 they are clinically healthy, (i. e. the physician would have no reservations vaccinating with FSME-IMMUN NEW outside the scope of a clinical trial);

 their parents/legal guardians understand the nature of the study and agree to its provisions;

 written informed consent is available from both parents/legal guardians,

 for Germany/Austria: additional written informed consent is available for children older than 8 years

 they or their parents/legal guardians agree to keep a volunteer diary.

 For safety reasons, female volunteers who have reached sexual maturity at study start have to meet the following additional inclusion criteria:

 - negative pregnancy test at study entry;

Exclusion criteria: :

 Children and adolescents will be excluded from participation in this study if they:

 have a history of any TBE vaccination;

 have a history of TBE infection;

 have a history of allergic reactions to one of the components of the vaccine;

 suffer from a disease (e.g. autoimmune disease) or are undergoing a form of treatment (e.g. systemic corticosteroids, chemotherapeutics) that can be expected to influence immunological functions;

 are known to be HIV positive (a special HIV test is not required for the purpose of the study);

 have received banked blood or immunoglobulins within one month of study entry;

 have a history of vaccination against yellow fever and/or Japanese B-encephalitis;

 suffer from hemorrhagic diathesis;

 are participating simultaneously in another clinical trial;

 if female: are pregnant or breastfeeding.

 Volunteers who meet the inclusion/