Global Study of Women's Health

Summary: Endometriosis, a condition in which the lining of the uterus grows on nearby tissues, is a common condition that affects women of reproductive age worldwide. The diagnosis of endometriosis is usually made at surgery. The most common symptom is pelvic pain. This pain may occur at the same time as menstrual bleeding, at other times of the cycle, or during or after sexual intercourse. Previous studies reveal the diagnosis of endometriosis is often delayed between 8 and 12 years after the first symptoms. Women with chronic pelvic pain report a lower quality of life. No studies, however, have been conducted to assess whether women with endometriosis-related pelvic pain are affected differently than those with pelvic pain from other or no identifiable causes.~This large-scale study is designed to gather prospective epidemiological data on the impact of and risk factors for endometriosis across countries worldwide. A study of this scale and scope has never been performed; it is anticipated that the study will provide novel insights into the effects of the condition and associated symptoms on women s lives across different countries, as well as explore differences in the effects of various potential risk factors.~This is an international study conducted at more than 20 sites worldwide and coordinated by Oxford University in the United Kingdom. At the National Institutes of Health, 250 premenopausal women between 18 and 45 years of age who are having their first diagnostic laparoscopy or laparoscopy for tubal sterilization will participate. None will have had a prior diagnosis of endometriosis through surgery. Women will be informed about the study when their laparoscopy is scheduled.~Procedures~Patient completion of an online questionnaire before scheduled surgery. The following will be assessed by the questionnaire:~Quality of life~General gynecologic and medical history~Family history~General information~Use of health care services~Risk factors~Surgeon completion of questionnaire about surgical findings.~Follow-up: Women who consent will be contacted every 1 2 years.
Inclusion criteria: inclusion criteria:

 A patient who meets all of the following criteria is eligible for the study:

 Premenopausal female 18 to 45 years of age

 Attending for her first diagnostic laparoscopy or for laparoscopy for tubal sterilisation

 Has no previous history of endometriosis diagnosis through surgery

Exclusion criteria: :

 A patient who meets any of the following criteria is ineligible for the study:

 Already has a surgically-confirmed diagnosis of endometriosis

 Aged less than18 or greater than 45

 Aged 18-45 but post-menopausal

['Endometriosis', 'Infertility', 'Chronic Pelvic Pain', 'Tubal Ligation']

Endometriosis
Infertility
Chronic Pelvic Pain
Tubal Ligation


Immediate Effects Cervicothoracic Manipulation Versus Passive Upper Trapezius Stretch

Summary: The proposed project seeks to evaluate the influence of cervicothoracic (CT) manipulation and passive stretching to the upper trapezius on pressure pain thresholds and range of motion (ROM) in individuals without recent complain of neck pain.
Inclusion criteria: inclusion criteria:

 1. No current history or past history of neck pain; able to lie on back or stomach without difficulty

Exclusion criteria: :

 'Red flag' items indicated in your Neck Medical Screening Questionnaire such as history of a tumor, bone fracture, metabolic diseases, Rheumatoid Arthritis, osteoporosis, severe atherosclerosis, prolonged history of steroid use, etc.

 History of neck whiplash injury

 Diagnosis from your physician of cervical spinal stenosis (narrowing of spinal canal) or presence of symptoms (pain, pins and needles, numbness) down both arms

 Presence of central nervous system involvement such as exaggerated reflexes, changes in sensation in the hands, muscle wasting in the hands, impaired sensation of the face, altered taste, and presence of abnormal reflexes

 Evidence of neurological signs consistent with nerve root entrapment (pinched nerve in the neck)

 Prior surgery to your neck or upper back

 A medical condition which may influence assessment of pain or pressure pain thresholds (i.e. taking analgesics, sedatives, history of substance abuse, or cognitive deficiency)

 Diagnosis from your physician of fibromyalgia syndrome

 Currently pregnant, or could be pregnant

['Upper Trapezius Stretch', 'Cervicothoracic manipulation', 'No intervention']

Upper Trapezius Stretch
Cervicothoracic manipulation
No intervention


Ease of Use and Correct Use Study of Placebo ELLIPTA® Inhaler in COPD Subjects

Summary: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The mainstay for treatment involves the use of inhaled medications, including short and/or long-acting bronchodilators along with inhaled corticosteroids. For inhaled medications, the choice of inhalation device is an important consideration because an inadequate technique reduces the effects of inhalation. Therefore, the development of an easy-to-use inhaler that delivers the drug to the lungs effectively, is important. This study will assess the correct use of the ELLIPTA inhaler by subjects with COPD and to assess ease of use of the ELLIPTA inhaler, as rated by those subjects determined to be using the inhaler correctly. Study will be divided into two visits i.e. Screening/Visit 1 (day 1) and Visit 2 (Day 28 +/-2) with a phone call on Day 8+/-2 days of Visit 1 to assess safety. In this multi-center, single-arm, randomised (to receive one of two versions of the ELLIPTA inhaler Ease of Use questionnaires), open-label, placebo study, only subjects who are have never used the ELLIPTA inhaler before and have an established diagnosis of COPD and receiving COPD therapy and are able to demonstrate correct use of the ELLIPTA inhaler at Visit 1 will be considered eligible to participate in this study. Approximately 252 subjects will be screened with an expectation of 208 subjects completing the study while demonstrating correct ELLIPTA inhaler use at visit 2.~ELLIPTA is a registered trademark of the GlaxoSmithKline Group of Companies.
Inclusion criteria: inclusion criteria:

 Age: >=40 years of age at Visit 1

 Diagnosis of COPD with a documented history of COPD for at least one year, in accordance with the definition by the American Thoracic Society/European Respiratory Society.

 Severity of Disease: Post albuterol/salbutamol forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) ratio <0.70 and FEV1 <=70% of predicted obtained within two years of Visit 1.

 Smoking History: Current or former (defined as subjects who have quit smoking for at least 3 months prior to Screening/Visit 1) cigarette smokers with a >10 pack-year smoking history (Number of pack years = [number of cigarettes per day divided by 20] x number of years smoked [e.g., 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]).

 Current COPD Therapy: Currently receiving maintenance (with one or more long-acting bronchodilators, such as a long-acting muscarinic antagonist (LAMA; also known as a long-acting anti-cholinergic) or long-acting beta 2-agonist (LABA) inhaler therapy (with no prior or ongoing use of ELLIPTA inhaler) for the treatment of COPD. Subjects must be able to continue using their currently prescribed COPD maintenance inhaler therapy throughout the study and as needed short acting beta-adrenergic agonist (SABA) for rescue use.

 Ability to Use Inhalers: Subject must be able to demonstrate correct use of ELLIPTA inhaler within three attempts at Visit 1.

 Males

 Females who are not pregnant or not planning a pregnancy during the study or not lactating.

 Informed Consent: Capable of giving signed and dated written informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

 Subject understands and is willing, able, and likely to comply with study procedures and restrictions.

 Subject must be able to read, comprehend, and record information in English.

Exclusion criteria: :

 A subject will not be eligible for inclusion in this study if any of the following criteria apply

 Asthma: Subjects with a current primary diagnosis of asthma.

 COPD medications: Receiving only inhaled short-acting beta-adrenergic agonists, i.e., albuterol as their daily COPD therapy (as needed [prn] or regularly scheduled); Has changed maintenance COPD treatment within 4 weeks prior to Screening/Visit 1 or plans to change COPD treatment within 4 weeks of Visit 1.

 COPD/Exacerbations/Hospitalization: Subjects that have experienced a COPD exacerbation requiring systemic corticosteroids (oral, parenteral or depot) and/or antibiotics within four weeks of Visit 1. A subject must not have had any hospitalization for COPD within three months prior to Visit 1; Subjects with uncontrolled COPD, in the investigator's judgment that would affect subject's ability to evaluate ease of use and correct use.

 Other Respiratory Disorders: Subjects with other respiratory disorders, including active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.

 Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening/Visit 1.

 Oxygen: Use of long-term oxygen therapy (LTOT; defined as oxygen therapy prescribed for greater than 12 hours per day) or nocturnal oxygen.

 Other Disease Abnormalities: Historical or current evidence of clinically significant or rapidly progressing or unstable cardiovascular, neurological, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the analysis if the disease/condition exacerbated during the study; Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.

 Compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures, or unable to continue their current COPD medications.

 Alcohol and Drug Abuse: A known or suspected history of alcohol or drug abuse within the last 2 years.

 A history of hypersensitivity to any components of the study inhaler (e.g., lactose, magnesium stearate). In addition, patients with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates participation will also be excluded.

 Prior or Ongoing use of the ELLIPTA inhaler (including both investigational and commercially available product).

 Investigational Product: Subjects who have received an investigational drug and/or medical device within 30 days of entry into this study (Screening/Visit 1), or within five drug half-lives of the investigational drug, whichever is longer.

['Pulmonary Disease, Chronic Obstructive']


Whole Body Vibration Therapy in Boys With Duchenne Muscular Dystrophy

Summary: Whole-body vibration therapy (WBVT) is a novel, non-pharmacological intervention aimed at improving muscle strength and endurance as well as bone density. It holds promise for children with neuromuscular disorders such as Duchenne muscular dystrophy (DMD) since muscle weakness results not only from muscle breakdown but also physical inactivity and muscle disuse atrophy. Weak DMD patients may increasingly limit their physical activity due to fear of falling or loss of independence (e.g. difficulty rising to stand without assistance). Prolonging the length of time boys with DMD are ambulatory is important for delaying complications of this disease (lung hypoventilation, scoliosis) as well as maintaining bone health. We propose to conduct a pilot study of WBVT in young boys with Duchenne muscular dystrophy (DMD). The primary outcome will be to document safety and feasibility of WBVT in this patient population. The secondary outcomes will evaluate changes in muscle strength and endurance. Bone health will also be examined as part of routine clinical care. The study will include 20 ambulatory boys with DMD; patients will be randomized (1:1 allocation) into 2 groups: WBVT treatment or no WBVT treatment (controls). Treatment groups will consist of 10 boys undergoing daily WBVT in an 8-week, open-label trial.
Inclusion criteria: inclusion criteria:

 Diagnosis of Duchenne muscular dystrophy confirmed by at least one of the following:

 Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical presentation consistent with typical DMD

 Positive gene deletion test (missing one or more exons) in the central rod domain (exons 25-60) of dystrophin, where reading frame can be predicted as out-of-frame, and clinical presentation consistent with typical DMD

 Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, or other mutation resulting in a stop codon mutation) definitively associated with DMD, and clinical presentation consistent with typical DMD

 Age between 5 - 14 yrs old (inclusive)

 Positive Gower sign (indicating ability to rise from the floor & presence of proximal muscle weakness).

 Able to walk 10 meters in <12 seconds

 Able to stand upon WBVT plate (with knees flexed) for entire treatment protocol (i.e. 15-minutes)

 Stable absolute dose of glucocorticoids (i.e. prednisone or deflazacort) for at least 3 months prior

 Stable absolute doses of all medication that may affect muscle function (i.e. coenzyme Q10, green tea extract, creatine, arginine, glutamine, nutritional supplements, etc.) for at least 3 months prior

 Stable absolute dose of all medication that may affect bone metabolism (i.e. vitamin D and calcium supplementation) for at least 3 months prior

Exclusion criteria: :

 Clinical presentation, genetic testing and/or muscle biopsy consistent with Becker muscular dystrophy

 History of recent surgery (within past 6-months)

 History of a recent fracture (long-bone or vertebral) within past 6-months.

 Acute inflammatory processes of lower extremities (e.g. cellulitis, etc) due to risk of pain and/or worsening inflammatory process

 History of venous thrombosis (theoretically risk of inducing thromboembolic event).

 History of kidney or bladder stones

 History of uncontrolled seizures or severe migraines

 History of cardiac arrhythmia

 Intracranial pathology or hardware (e.g. ventriculoperitoneal shunt, cochlear implant).

 Use of any investigational or experimental products within last 6-months and/or concomitant participation in another study

 Inability or refusal to follow the study requirements (e.g. autism, severe cognitive or behaviour problems)

 Inability or refusal to provide informed consent (parent) and/or assent (child)


Influence of Area of Brain Damage on Brain Reorganization After Chronic Stroke

Summary: This study will examine how the brain rewires itself to make up for the lack of movement many people with stroke experience. It will try to determine if the rewiring differs depending on the location of the stroke and the amount of time since the stroke occurred. For some stoke patients, weakness may persist, while others recover completely after time. It is not known which parts of the brain are involved in the recovery of different types of stroke and if the type of stroke affects recovery.~People 18 years of age and older who have had subacute thromboembolic or hemorrhagic stroke more than 3 months before enrolling may participate in this study.~Participants come to the NIH Clinical Center three times every 2 years for up to 10 years. At the first visit, patients have a neurological examination and perform tests of motor abilities such as lifting small objects, turning cards, using a spoon, stacking checkers and lifting cans during a short period of time as rapidly as possible.~At the second visit, subjects have structural magnetic resonance imaging (MRI) scans of the brain. MRI uses a strong magnetic field and radio waves to obtain images of body organs and tissues. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the scan, the subject lies on a table that can slide in and out of the cylinder, wearing earplugs to muffle loud knocking noises associated with the scanning process. Total scan time is about 30 minutes~At the third visit, subjects perform some simple movement tasks during functional MRI (fMRI) scans. The procedure is the same as with structural MRI, except that subjects are asked to perform simple movement tasks in the scanner. Before the fMRI scans, electrodes are attached to the subject's arms and legs to monitor muscle activity (surface electromyography). Total scan time is about 1.5 hours. Movement tasks might include pinching a force-measuring instrument with the fingers, pressing different keys on a keyboard as fast as possible, inserting pegs into small holes on a board, lifting weights, flipping cards or similar activities.
Inclusion criteria: inclusion criteria:

 Patients must be aged 18 or above with subacute (at least 3 months post stroke) thromboembolic or hemorrhagic strokes with impaired motor function in at least one of the limbs but capable of performing the required motor tasks. Assessment of the initial functional state will be taken at the initial visit at the NINDS Stroke Neurorehabilitation Clinic. Patients with additional stroke(s) during the length of the protocol will not be excluded from the study if the conditions stated in the
Exclusion criteria:  are satisfied.

['Central Nervous System Disease', 'Cerebrovascular Accident', 'Stroke']

Central Nervous System Disease
Cerebrovascular Accident
Stroke


Heart Failure Registry

Summary: The purpose of this registry is to compile a large clinical database on the medical management of patients hospitalized with acute heart failure, using information collected from acute care hospitals across the United States.
Inclusion criteria: inclusion criteria:

 Received or is eligible to receive a principal hospital discharge diagnosis of HF or decompensated HF is present as determined clinically by the patient care team

Exclusion criteria: :

 Heart Failure is present as a co-morbid condition, but is not a principal focus of diagnosis or treatment during this hospitalization episode


Arixtra PE Study- Outpatient Management of Stable Acute Pulmonary Embolism: Once Daily Subcutaneous Fondaparinux

Summary: To assess the safety and efficacy of outpatient treatment using fondaparinux and oral Vit K antagonist, warfarin (Coumadin) in patients with stable acute pulmonary embolus (APE)when initial therapy is administered in the hospital. Prospectively validate risk stratification criteria for predicting patient suitability for outpatient treatment of acute pulmonary embolism.
Inclusion criteria: inclusion criteria:

 Patients enrolled into the trial must meet all of the following criteria:

 At least 18 years of age and able to provide informed consent

 Objectively confirmed symptomatic APE [intraluminal filling defect on spiral computed tomography (CT) or pulmonary angiography, or high- probability ventilation-perfusion (V/Q)lung scan

 Stable and low risk defined as:

 Hemodynamically stable (HR≤120, no hypotension, no tachypnea, no mental status change, no shock state)

 O2 supplement ≤4 L/NC

 Lack of electrocardiographic or echocardiographic evidence for new RV strain

 Radiographically non-massive PE (absence of saddle emboli on PA gram or spiral CT, perfusion defect on V/Q scan <50%

 No significant cardiac abnormalities (EF<35%, unstable angina, positive stress test within the past 3 months without revascularization) or pulmonary disease (severe COPD, pulmonary HTN).

 Negative cardio-specific biomarkers obtained at baseline (TNT, BNP)

 No moderate or severe RV dysfunction on echocardiogram

 Women of childbearing potential must have a negative pregnancy test (urine or serum) within 24 hours of enrollment

Exclusion criteria: :

 Patients meeting one or more of the following criteria are not eligible for enrollment into the trial:

 In the opinion of the clinician, the patient should receive in-patient standard medical therapy

 Contraindication for anticoagulation therapy (active or recent bleeding, recent surgery, bleeding diathesis, recent neurologic event)

 Is receiving therapeutic doses of UFH or LMWH for >24 hours

 Thrombolytic or glycoprotein IIb/IIIa agents administered within 24 hours prior to enrollment

 Platelet count <100,000

 Creatinine clearance <30 mL/min at time of enrollment

 Presence of neuraxial anesthesia and/or post-operative indwelling epidural catheter

 Known history of antiphospholipid antibody syndrome

 Weight >150 kg (330.7 lbs) or <45 kg (99.2 lbs)

 Life expectancy ≤3 months

 Associated arterial thrombosis

 Heparin induced thrombocytopenia (HIT) diagnosed within the past 100 days

 IVC filter

 Any condition that in the opinion of the investigator will prohibit compliance with study procedures and treatment


Efficacy and Safety of Primovist in Chinese Patients

Summary: Participants who had been diagnosed or suspected by doctors to have focal liver lesions that need further evaluation in order to make an accurate diagnosis. Participants would need to have an enhanced magnetic resonance imaging (MRI) scan so that doctors could have further information about the number and characteristics of the focal liver lesions.~Participants were invited to take part in this clinical study. The purpose of this study was to evaluate Primovist, which is a liver-specific MRI contrast medium, on the efficacy of lesion detection and characterization, and tolerability in Chinese patients with known or suspected focal liver lesions.~Primovist, the investigational drug in this study, is a liver-specific MRI contrast medium developed by Bayer Schering Pharma AG. Its active substance is Gd-EOB-DTPA. Primovist was first approved in 2004 in Sweden followed by an approval in the European community, in Switzerland and Australia in the same year.~Procedures:~Before entry into the study and after entry of the study a physical examination was conducted, blood pressure and heart rate were measured, blood and urine samples were taken. Current medications and medical conditions (including suspected pregnancy) and medical and surgical history were elicited by doctors.~After entry into the study, participants were scheduled to have an MRI examination, which lasted about 25-35 minutes.~During the MRI examination, an initial MRI scan without contrast was acquired which followed by another MRI series after the intravenous administration of Primovist.~The following day participants were asked to return to the hospital for a follow-up safety evaluation.~Possible Benefit Participants were scheduled to receive an enhanced magnetic resonance imaging scan. Clinical studies indicated that Primovist increased the efficacy of detection and characterization of focal liver lesions by providing better contrast between the focal liver lesions and surrounding normal tissue. Primovist were shown to provide additional information regarding existence, number and characterization (lesion or non-lesion, malignant or benign) of these abnormalities.~Based on the experience with patients given Primovist, some adverse reactions were observed.~Most of undesirable effects were transient and of mild to moderate intensity. The most commonly noted adverse events (AEs) in subjects receiving Primovist for MRI were nausea and headache with an incidence of 1.1%. Other AEs that occurred in 0.5% of the subject population were feeling hot (0.8%), back pain (0.6%) and dizziness (0.5%).~All other AEs occurred in less than 0.5% of the patients, e.g. anxiety; coughing; eye disorder; fever; flatulence; generalized spasm; hypertension; injection site symptoms including edema, inflammation, and reaction; lightheadedness; parosmia; postural hypotension; taste perversion, motoric unrest; acute respiratory distress; fatigue; malaise; vomiting; palpitations, erythema, chest pain and back pain.~Coldness, warmth or pain at the injection site, injection site reaction, and injection site accumulation of fluid were rare. In very rare cases strong allergy-like reactions ranging to shock may occur.~Post-marketing tachycardia and restlessness have been reported. As in the case of other investigational drugs, there may also be unforeseen side effects.~Additional information concerning all Gadolinium- based contrast agents Primovist contains the rare earth metal gadolinium as active ingredient. There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some gadolinium-containing contrast agents (especially Omniscan) in patients with severe renal impairment. NSF is a systemic disease characterised by formation of connective tissue in the skin, which becomes thickened and hard, sometimes leading to contractures and joint immobility. The clinical course is usually progressive and currently no treatment is available. To date NSF has only been reported in association with some Gd-containing contrast agents, but the role of these contrast agents in the overall pathogenesis of the disease is still not completely understood.~No reports of patients with NSF after administration of Primovist® are known. The risk to trigger NSF in risk patients with severe renal impairment is considered to be low for Primovist® due to the low dose given and the additional excretion via feces. Furthermore the participation of patients with severe renal impairment are excluded from this study.~In case the participants were suffering from renal insufficiency, they were told to tell their doctors prior to application of the contrast agent. In case the participants experienced any new alterations of the skin following the administration of the contrast agent, they were told to contact their doctors as soon as possible after they had recognized these symptoms.
Inclusion criteria: inclusion criteria:

 Patients between 18 and 75 years of age inclusive.

 Patients (men or women) with at least one focal liver lesion, either identified or suspected by ultrasound (US), Computed Tomography (CT)/spiral-CT, conventional angiography, CT-angiography (CTA), CT-arterioportography (CTAP) or unenhanced / contrast-enhanced MRI* within 2 months before entering the study

 For reference, the following pathologies will meet the definition of 'focal liver lesions':

 Hepatocellular carcinoma

 Cholangiole carcinoma

 Metastasis

 Focal lymphoma

 Adenoma

 Focal nodular hyperplasia

 Hemangioma

 Abscess

 Focal liver fibrosis

 Regenerative nodules

 Focal fatty infiltration

 Hydatid cyst

 Liver cyst

 Focal sparing in fatty liver

 Others

 Patients willing to undergo study procedures including safety follow-up

 Patients who have undergone or who are scheduled to undergo the defined procedure for SOR within one month before or after the study MRI

 Women of child-bearing potential with negative urine pregnancy test result within 24 hours before contrast medium (CM) injection

 Patients who are fully informed about the study and have signed the informed consent form

Exclusion criteria: :

 Patients who have previously entered this study

 Patients who have received any contrast material within 24 hours before injection with study drug, or who are scheduled to receive any contrast material within 24 hours after injection

 Patients who are, or suspected to be, nursing

 Patients who require emergency treatment

 Patients with severely impaired hepatic or renal functions (e.g. serum glutamic-pyruvic transaminase (SGPT) twice the upper limit of reference range, acute renal failure)

 Patients who are clinically unstable and whose clinical course during the observation period is unpredictable (e.g. due to previous surgery, acute myocardial infarction)

 Patients with any physical or mental status that interferes with the signing of informed consent

 Patients with known anaphylactoid or anaphylactic reaction to any contrast media or hypersensitivity to any allergen including drugs

 Patients with a contraindication for MRI

 Patients who are scheduled for liver biopsy/surgery or other surgeries within 24 hours after injection with contrast media, or who would have a biopsy within 24 hours before planned injection with contrast media

 Patients who are likely to have any therapy or change in therapy between the study MRI and the procedures for the SOR

['Gadoxetic Acid Disodium (Primovist, BAY86-4873)']

['Known or Suspected Focal Liver Lesions']


Effects of a Novel Dietary Intervention on Body Composition After Laparoscopic Gastric Bypass Surgery

Summary: We propose to compare the standard of care with the use of a novel medical food in 6 bariatric surgery patients by measuring outcomes of body composition, quality of life, hair loss, muscle strength, resting energy expenditure, and biochemical parameters.
Inclusion criteria: inclusion criteria:

 Obese and morbidly obese women (BMI 30 - 50)

 25 years and older undergoing laparoscopic gastric bypass surgery

 Present with at least either metabolic syndrome or diabetes

Exclusion criteria: :

 Have smoked in the past 4 weeks

 Pregnant

 Allergic or intolerant to ingredients used in the study (e.g. soy and THIAA)

 There is a sound medical, psychiatric and/or social reason as determined by the Principal Investigator (PI) that makes the subject unsuitable for the study


Strategies for Suspected Pulmonary Embolism in Emergency Departments

Summary: Aims: 1) To evaluate the effectiveness of two interventions aimed at improving the management of patients with suspected pulmonary embolism: Written guidelines and Computer-Assisted Decision Support (CADS). 2) To evaluate the impact of electronic reminders on the appropriateness of the treatment of patients with suspected PE~Design: Pragmatic, unblinded, cluster randomised controlled study.~Setting: 20 French Emergency Departments~Patients: Out patients suspected of having pulmonary embolism~Methods: Emergency physicians will prospectively complete a standardized electronic form on Personal Data Assistant (PDA), including patients' characteristics, the clinical probability if assessed, the diagnostic tests performed, the treatments initiated and the final diagnostic and therapeutic decisions. Patients will be interviewed at the end of a 3-month follow-up period using a standardized questionnaire.~The reference rate of appropriateness of the diagnostic management before intervention will be assessed in each centre. At the end of this preliminary period, the centres will be randomized in two fold two groups according to a factorial design with stratification on their reference level of appropriateness. Half of the centres will have written guidelines and half a Computer-Assisted Decision Support for the diagnosis of PE on the PDA. In each of these two main groups, half of the centres will have electronic reminders on their PDA concerning the treatment of PE.~Judgment criteria~Main : Rate of strategies considered as validated according to the results of the systematic review and meta-analysis.3~Secondary judgment criteria (diagnosis):~Rate of strategies considered as validated or acceptable according to the opinion of international advisors.~Rate of thromboembolic-events during a 3-month follow-up period in patients for whom pulmonary embolism will be ruled out~Costs of the diagnostic management~Secondary judgment criteria (treatment):~Delay between Emergency Department admission and the first dose of antithrombotic treatment in patients with high clinical probability of PE according to the Revised Geneva Score~Rate of inappropriate treatment according to international recommendations for patients with confirmed PE.~Number of patients: By estimating that the rate of appropriateness would be 55% in the written guidelines group, 1331 patients are necessary to highlight an absolute superiority of 15% in the CADS group (rate of conformity of 70%).~The number of patients will be adjusted at the end of the preliminary period according to the level of appropriateness before interventions considering that it will improve less than 5% in the written guidelines group.
Inclusion criteria: inclusion criteria:

 patient with suspected pulmonary embolism

 prescription of a specific paraclinical diagnostic investigation or start of a specific treatment for pulmonary embolism

Exclusion criteria: :

 confirmation or exclusion of pulmonary embolism before admission in emergency department

 confirmation of deep venous thrombosis before admission in emergency department

 suspicion of pulmonary embolism during hospitalization (in-patient)

 suspicion of pulmonary embolism without investigation realization

 patient already included in the study

 patient refusing the utilization of his data for the study

['Computer-Assisted diagnostic Decision Support', 'written diagnostic guidelines', 'electronic therapeutic reminders']

['Quality of Health Care', 'Pulmonary Embolism']

Quality of Health Care
Pulmonary Embolism


Preconditioning Shields Against Vascular Events in Surgery

Summary: Major vascular surgery involves operations to repair swollen blood vessels, clear debris from blocked arteries or bypass blocked blood vessels. Patients with these problems are a high-risk surgical group as they have generalized blood vessel disease. These puts them at risk of major complications around the time of surgery such as heart attacks , strokes and death. The mortality following repair of a swollen main artery in the abdomen is about 1 in 20. This contrasts poorly with the 1 per 100 risk of death following a heart bypass. Simple and cost-effective methods are needed to reduce the risks of major vascular surgery. Remote ischaemic preconditioning (RIPC) may be such a technique. To induce RIPC, the blood supply to muscle in the patient's arm is interrupted for about 5 minutes. It is then restored for a further five minutes. This cycle is repeated three more times. The blood supply is interrupted simply by inflating a blood pressure cuff to maximum pressure. This repeated brief interruption of the muscular blood supply sends signals to critical organs such as the brain and heart, which are rendered temporarily resistant to damage from reduced blood supply. Several small randomized clinical trials in patients undergoing different types of major vascular surgery have demonstrated a potential benefit. This large, multi-centre trial aims to determine whether RIPC can reduce complications in routine practice.
Inclusion criteria: inclusion criteria:

 Age greater than 18 years

 patient willing to give full informed consent for participation

 Patients undergoing elective carotid endarterectomy or

 Patients undergoing open abdominal aortic aneurysm repair or

 Patients undergoing endovascular abdominal aneurysm repair or

 Patients undergoing surgical lower limb revascularisation (suprainguinal or infrainguinal)

Exclusion criteria: :

 Patients less than 18 years of age

 Patients who are unable or unwilling to give full informed consent

 Pregnancy

 Significant upper limb peripheral arterial disease

 Patients on glibenclamide or nicorandil (these medications may interfere with remote ischaemic preconditioning)

 Patients with an estimated pre-operative glomerular filtration rate < 30mls/min/1.73m2

 Patients with a history of myocarditis, pericarditis or amyloidosis

 Patients undergoing Fenestrated or branched EVAR.

['Abdominal Aortic Aneurysm', 'Carotid Atherosclerosis', 'Critical Lower Limb Ischaemia']

Abdominal Aortic Aneurysm
Carotid Atherosclerosis
Critical Lower Limb Ischaemia


Crossover Vaccination of Women Previously Randomized Into Protocol 04-C-N191

Summary: Background:~- National Cancer Institute Protocol 04-C-N191, also known as the Costa Rica Vaccine Trial, was a double-blind controlled study of the effectiveness of an experimental human papillomavirus (HPV) vaccine in preventing cervical cancer in young women in Costa Rica. Costa Rica was part of the first large study to show the association between HPV and cervical cancer, and the study contributed greatly to the understanding of this association. The women who have participated in the vaccine trial in Costa Rica are reaching the end of the follow-up period offered in the vaccine trial protocol, and as a result they are being offered the chance to have complementary vaccinations against HPV, hepatitis A, and hepatitis B.~Objectives:~To offer participants in the Costa Rica Vaccine Trial the vaccine that they did not receive during the masked portion of the trial (HPV vaccine or hepatitis A vaccine) and hepatitis B vaccination.~To collect information about exposure to known and suspected risk factors for HPV infection and cervical cancer from women who are receiving vaccination against HPV at crossover.~Eligibility:~- Women who participated in National Cancer Institute Protocol 04-C-N191.~Design:~All participants will be offered vaccination against hepatitis B.~Women who received the hepatitis A vaccine during the trial will be offered vaccination against HPV.~Women who received the HPV vaccine during the trial will be offered vaccination against hepatitis A.~Appropriate vaccinations (including a combined hepatitis A and hepatitis B vaccine) will be available to reduce the number of injections that participants will be asked to receive.~All vaccines will be given according to the manufacturer's specifications for appropriate length of time between vaccine doses.
Inclusion criteria: inclusion criteria:

 To be eligible to receive crossover vaccination, participants must fulfill all of the following inclusion criteria:

 Participation Status: Women previously randomized into the HPV-16/18 vaccine trial 04-C-N191, also known as the Costa Rica Vaccine Trial.

 Planned Residence: Residents of Guanacaste or Puntarenas Province or willingness to visit one of the study clinics for participation.

 Consent: Written informed consent obtained prior to enrollment into the crossover protocol.

Exclusion criteria: :

 The following criteria will be checked for all potential participants at the time of enrollment. If any apply, the participant will not be included in the study.

 History of (a) allergic reaction (e.g., difficulty breathing) after receipt of any vaccine, (b) hypersensitivity to latex.

 History of vaccine related adverse events during the vaccination phase that, at the discretion of the investigators, preclude vaccination during the crossover phase.

 Are receiving vaccination with Cervarix , are sexually experienced and of childbearing potential (i.e., not surgically sterilized), and are unwilling to use an effective method of birth control for 30 days before vaccination until 60 days after the last Cervarix vaccination (approximately 9 months). Acceptable forms of birth control include abstinence, surgical sterilization, hormonal contraceptives (e.g., oral, injectable, implant, and patch), intrauterine devices, and diaphragm or condom.

 History of chronic condition that per attending doctor opinion precludes her from receiving vaccination (e.g., no proper treatment available or participant is unwilling to stay under proper treatment).

 The participant has a diagnosed autoimmune illness (per the specific requirement of the INCIENSA IRB).

 The vaccine or vaccines the participant is interested in receiving are contraindicated in her case.

['Cervical Neoplasia', 'HPV Infections']


ED Intervention to Reduce Risky Behaviors in Drivers

Summary: Disability and death from injury remain a persistent problem in the U.S. and risk-taking behaviors are known to contribute to injury. Healthy People 2010 set goals to reduce deaths caused by injury: Motor vehicle crashes are often predictable and preventable. Increased use of seat belts and reductions in driving while impaired are two of the most effective means to reduce the risk of death and serious injury of occupants in motor vehicle crashes. One preventive strategy is to establish screening and intervention procedures that can be administered in the ED to young adults who have risky driving practices and problem drinking. Goal: The specific aim of this prospective, randomized controlled trial is to test the effectiveness of a brief intervention to limit risky driving behaviors (risky driving practices, lack of seat belt compliance) and problem drinking in drivers during an ED visit. In addition, the trial will result in a benefit-cost analysis from the perspectives of both society as a whole and hospitals in particular. Methods: Young adults 18 to 44 years will be screened for problem drinking and risky driving practices during an ED visit. Subjects who screen positive for problem drinking and risky driving will be randomized to one of three groups: No Contact Control Group (NCG: after informed consent, subjects receive no screening or intervention until 12 months after injury). Contact Control Group (CCG: subjects screened at baseline and every three months for 12 months but no intervention), and a Brief Intervention Group (BIG: subjects receive screening and brief intervention with data collection points every three months for 12 months). A total of 133 subjects per group (N=400) will be enrolled. The intervention will consist of a 20 minute nurse visit in the ED and a booster intervention at 7-10 days after ED discharge. All subjects will be telephoned at 3, 6, 9, and 12 months by interviewers blinded to condition. Outcomes of interest include reported alcohol use, risky driving behaviors, driving citations, adverse health outcomes, and costs (health care utilization, property damage, travel delays, lost work productivity, criminal justice expenses, and monetarized adverse health outcomes). Analysis: Power analysis suggests that 133 subjects in each arm of the trial will have sufficient power to detect a difference of the main outcome variables of interest. A variety of regression techniques, including individual growth curve modeling and event history analysis, will be used to test the proposed hypotheses.
Inclusion criteria: inclusion criteria:

 Screen Positive for a drinking problem in the ED

Exclusion criteria: :

 <18years or >44years old


Aripiprazole in Late Life Bipolar Disorder

Summary: The purpose of this research study is to analyze the effectiveness and tolerability of a new medication, aripiprazole (Abilify), in individuals age 50 years and older who have bipolar disorder (manic-depressive illness).
Inclusion criteria: inclusion criteria:

 Must have Bipolar disorder as confirmed by the Mini Neuropsychiatric Interview (MINI)

 Must be age 50 or older

 Must have sub-optimal response to current psychotropic management including at least one of the following:

 Behaviors and symptoms of irritability, agitation, mood liability or diminished ability to interact with others in their place of residence

 Diminished ability to take care of basic personal needs in their place of residence due to symptoms of bipolar disorder

 Intolerance to current psychotropic medications; and

 Must live in the Northeast Ohio area.

Exclusion criteria: :

 An unstable medical illness, or a medical illness, which in the opinion of the study investigators, is likely to affect the outcome of the study

 DSM-IV substance dependence (except nicotine or caffeine) within the past 3 months; or

 Receiving carbamazepine.


Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease

Summary: The purpose of this study is to determine if fluticasone furoate/vilanterol improves survival in patients with chronic obstructive pulmonary disease with a history of or increased risk of heart disease.
Inclusion criteria: inclusion criteria:

 Type of subject: outpatient.

 Informed consent: Subjects must give their signed and dated written informed consent to participate.

 Gender: Male or female. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception.

 Age: >=40 and <=80 years of age at Screening (Visit 1).

 Tobacco use: Subjects with a current or prior history of >=10 pack-years of cigarette smoking at screening (Visit 1). Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.

 Airflow Obstruction:

 Subjects with a measured post-albuterol/salbutamol forced expiratory volume in 1 second (FEV1)/(forced vital capacity)FVC ratio of <=0.70 at Screening (Visit 1).

 Subjects with a measured post-albuterol/salbutamol FEV1 >=50 and <=70% of predicted normal values calculated using NHANES III reference equations [Hankinson, 1999; Hankinson, 2010] at Screening (Visit 1).

 Post-bronchodilator spirometry will be performed approximately 15 minutes after the subject has self-administered 4 inhalations (i.e., total 400mcg) of albuterol/salbutamol via a metered dose inhaler (MDI )with a valved-holding chamber. The FEV1/FVC ratio and FEV1 percent predicted values will be calculated.

 Symptoms of COPD: Subjects must score 2 or higher on the modified Medical Research Council Dyspnea scale (Visit 1)

 Cardiovascular disease:

 For patients >= 40 years of age: any one of the following:

 Established (i.e. by clinical signs or imaging studies) coronary artery disease (CAD) Established (i.e. by clinical signs or imaging studies) peripheral vascular disease (PVD) Previous stroke Previous MI Diabetes mellitus with target organ disease OR

 For patients >=60 years of age: any 2 of the following:

 Being treated for hypercholesterolemia Being treated for hypertension Being treated for diabetes mellitus Being treated for peripheral vascular disease

Exclusion criteria: :

 Pregnancy: Women who are pregnant or lactating.

 Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they also have a current diagnosis of COPD).

 alpha 1-antitrypsin deficiency: Subjects with known alpha-1 antitrypsin deficiency as the underlying cause of COPD.

 Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.

 Lung resection or transplantation: Subjects with lung volume reduction surgery within the 12 months prior to Screening or having had a lung transplant.

 A moderate/severe COPD exacerbation that has not resolved at least 14 days prior to Visit 1 and at least 30 days following the last dose of oral corticosteroids (if applicable).

 Current severe heart failure (New York Heart Association class IV). Subjects will also be excluded if they have a known ejection fraction of <30% or if they have an implantable cardioverter defibrillator (ICD).

 Other diseases/abnormalities: Any life-threatening condition with life expectancy <3 years, other than vascular disease or COPD, that might prevent the subject from completing the study.

 End stage chronic renal disease: Subjects will be excluded if on renal replacement therapy (hemodialysis or peritoneal).

 Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g. beta-agonists, corticosteroid) or components of the inhalation powder (e.g. lactose, magnesium stearate). In addition, patients with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates the subject's participation will also be excluded.

 Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.

 Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e. <=12 hours per day) is not exclusionary.

 Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study or the potential compliance to study procedures.

 Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.

 Additional medication: Use of the following medications within the following time intervals prior to Visit 1 or during the study (unless otherwise specified):

 Medication No use within the following time intervals prior to Screening or thereafter at any time during the study (unless otherwise specified) Inhaled Long acting beta-agonists (LABA) 48 hours ICS/LABA combination products 48 hours Inhaled corticosteroids 48 hours Tiotropium 1 week Systemic, Oral, parenteral, intra-articular corticosteroids 30 days (oral and systemic corticosteroids may be used to treat COPD exacerbations during the study) Cytochrome P450 3A4 strong inhibitors including but not limited to antiretrovirals (protease inhibitors) (e.g.Indinavir, Nelfinavir, Ritonavir, Saquinavir); Imidazole and Triazole anti-fungals (e.g. Ketaconazole, Itraconazole); Clarithromycin, Telithromycin, Amiodarone, and Nefazodone 6 weeks Grapefruit is allowed up to Visit 1, then limited to no more than one glass of grapefruit juice (250 mL/ 8 ounces) or one grapefruit per day Any other investigational drug 30 days or 5 half lives whichever is longer.

['fluticasone furoate/vilanterol', 'fluticasone furoate', 'vilanterol', 'Placebo']

fluticasone furoate/vilanterol
fluticasone furoate
vilanterol
Placebo


Promoting Parental Skills and Enhancing Attachment in Early Childhood

Summary: Child psychological/behavioural disorders such as withdrawal may persist when the psychosocial context is unfavourable. Health promotion strategies (Olds' paradigm) have proved their efficacy in vulnerable populations. CAPEDP project sets out to evaluate a program of home visits in France
Inclusion criteria: inclusion criteria:

 Being less than 26 years old

 Being pregnant for less than 27 weeks

 Being primiparous

 Living in the study area

 Being socially vulnerable: less than 12 years of education AND/OR socially isolated AND/OR eligible for a public health insurance for people with low resources.

Exclusion criteria: :

 Refusal to participate

 Not able to speak French

 Having a medical follow-up which necessitates regular contact with health professional

 Not having health insurance

 Persons for whom follow up at 27 months is impossible (evaluation at baseline)

['Promoting Parental Skills and Enhancing Attachment', 'had home visits by community workers during pregnancy']


My Health Coach Study

Summary: The My Health Coach Study seeks to determine if health coaching by a medical assistant can help patients have better sleep, a better diet, be more physically active or lose weight, according to the recommendation of their health care provider.
Inclusion criteria: inclusion criteria:

 adults age 21 and over

 referred by primary care physician for health coaching

 have telephone for follow-up

 English speaking

Exclusion criteria: :

 pregnant or trying to become pregnant

:

 pregnant or trying to become pregnant


Procalcitonin To Reduce Antibiotics in Chronic Obstructive Lung Disease (ProToCOLD)

Summary: Title: Pro-to-COLD, Procalcitonin to Chronic Obstructive Lung Disease,~COLD: Chronic Obstructive Lung Disease, Regarding: Patients hospitalized with suspected acute exacerbation of COPD + / - pneumonia.~Background: Patients with COPD exacerbation often get antibiotics. There is considerable criticism of this, many of these patients are not bacterially infected and the antibiotics overconsumption can lead to resistance development and side effects.~The purpose: To show that one can reduce the consumption of antibiotics among patients hospitalized for worsening of COPD disease in a population of Danish COPD patients by giving antibiotics depending on the value of the biomarker procalcitonin measured in the blood. A sub-objective is a validation study of mini VIDAS ® / Biomérieux equipment to the current gold standard in measuring procalcitonin, Kryptor/ BRAHMS.~Subjects: All patients with confirmed/suspected COPD admitted with COPD exacerbation to the Acute Admissions Unit/ Pulmonary dept. in weekdays. Participants must be adults and be of age and there must be a signed informed consent.~Method: 1) Controlled (Quasi-randomized): Even and uneven (concealed) digit of patient´s danish personal identification number, not last digit (gender-fixed) (CPR-number). Even = procalcitonin-guided, Uneven = Control.~2) Collect and analyze procalcitonin (PCT)-samples of patients in the PCT group at admission and then every 2 day. Samples analyzed throughout the week: Vital Status looked up 28 days after inclusion. Create a biobank in the study consisting of blood à 8 ml up to a maximum of 4 times taken for PCT measurements, the subsequent validation study of MiniVIDAS ®. Biobank destroyed 15 years after the completed project.~Statistical considerations:~Sample size / Sample Size:~A total of 120 patients (please see the basis for this estimate of the Protocol).~Analyze:~A) Antibiotics stopped on day 5 B) Defined Daily Doses Reads aloud, 1) narrow spectrum, 2) broad spectrum, and 3) a total of the two groups between the (Mann-Whitney U test) C) Hospitalization within 28 days after the first hospitalization the year - the two groups between (Mann-Whitney U test). Doctor Jens-Ulrik Jensen stands for analyzes. Statistics program SAS v. 9.1.3 is used.~Economics: The study funded by the participating departments.~Responsibility: The study was conceived and run by doctors in Pulmonary Medicine Department and Department of Clinical Pharmacology, both Bispebjerg Hospital and Department of Clinical Microbiology, Hvidovre Hospital.~Science Ethics: There has been a thorough research ethics discussion of the project in the project with emphasis on an assessment of the advantages and disadvantages that might be for the participating patients and society as a whole now and in the future. Conclusions A and B of this discussion is summarized as:~A. Advantages and Disadvantages: The treating physician has at any time the opportunity to start / continue antibiotic behandlling for the overall assessment whether PCT value. In addition, in the past, in large studies with a total of> 2000 patients, demonstrated that there are drawbacks to the use of antibiotics depending on a displayed value of PCT in patients hospitalized with acute exacerbations of COPD. Mortality and hospitalization will be monitored in this study. However, there may occur side effects to blood sampling, usually transient ecchymosis blood sampling site. If the strategy results in a reduced consumption of antibiotics, it is expected that the incidence of antibiotic-associated adverse events decreased - this for the benefit of the patient.~B. Usefulness for society: Based on the results from this study will be a high degree of certainty to conclude whether this new treatment strategy can provide benefits for future patients in the form of reduced antibiotic consumption, less antibiotic associated adverse events, reduced resistance development / selection among bacteria and overall lower economic costs. Based on these considerations, believes the project, the project can be carried out with respect for the participating subjects to integrity.~Quantity: It is expected to be included 120 patients in this scientific study. Database: data (case report forms) stored in archive of Pulmonary Medicine Department for 15 years. Create a database with the information. Personally identifiable data will only be present in the clinical hospital. During the completion of the experiment can provide essential health information about the subject's state of health. This will the subject be informed, unless clearly opted out of this on the consent form. The project reported to the Data Protection Agency.~Level: With blood sample (8 mL) on day 1 and then every 2 days in the intervention group (the active group), this part of routine blood sampling. At discharge stops blood and the patient should not attend the blood after discharge.
Inclusion criteria: inclusion criteria:

 3.3. inclusion criteria and Recruitment Doctors in Pulmonary Medicine Department, Bispebjerg Hospital, which is involved directly in the treatment of patients who are potential candidates can be created as investigator after proper information and training. Then, these doctors include patients. Inclusion is based on the following in-and
Exclusion criteria:  and after oral and written participant information.

 Inclusion: The following criteria must all be met for the patient can be First The patient must have confirmed / suspected COPD, and must be hospitalized with COPD exacerbation.

 Second The patient must be an adult (more than 18 years) and age. 3rd There must be a signed informed consent 4th Patients included only on weekdays.


Effects of Canola Oil on Blood Vessel Function in Peripheral Arterial Disease

Summary: The fatty acid composition of canola oil will have beneficial acute and chronic effects on vascular function in individuals with peripheral arterial disease.
Inclusion criteria: inclusion criteria:Healthy age-matched participants (acute phase of the study):

 Healthy volunteers, male or female, > 40 years of age;

 Body Mass Index 18-30;

 Glycated hemoglobin <6.5%;

 Fasting serum total cholesterol <4 mmol/L and triglycerides <2.5 mmol/L;

 Blood pressure <140/90 mm Hg;

 Ankle-brachial index of >0.9;

 Willing to comply with the protocol requirements;

 Willing to provide informed consent;

 Participants having completed another food-related study are eligible to participate if it has been more than 3 months since their participation.

 inclusion criteria, peripheral arterial disease participants (acute and chronic phases of the study):

 Male or female, > 40 years of age;

 Documented peripheral arterial disease including those with claudication as defined by an ankle brachial index of ≤0.90 or asymptomatic carotid stenosis of >50%; or who have had a previous intervention for peripheral arterial disease;

 Stable medication profile for the past 3 months with no changes anticipated for the duration of the acute or chronic phases;

 Willing to comply with the protocol requirements;

 Willing to provide informed consent;

 Participants having completed another food study are eligible to participate if it has been more than 3 months since the study was completed.

Exclusion criteria: , healthy age-matched participants (acute phase of the study):

 Currently smoking, or smoking within the last 6 months (Note: cigar smoking on an occasional basis will be permitted);

 Presence of a clinically diagnosed disease affecting the heart, liver, kidneys, lungs,gastrointestinal, endocrine or blood/immune systems that requires medical treatment;

 Taking any prescribed medication within the last 3 months with the exception of anti-depressants, birth control and hormone (estrogen) replacement therapy;

 Pregnancy;

 Amputation of upper or lower extremity on both sides;

 Has undergone a surgical procedure requiring local or general anesthetic within the last 3 months;

 History of gastrointestinal reactions or allergies to dietary oils and other ingredients in banana bread such as wheat and eggs;

 Daily consumption of omega-3 supplements.

['traditional canola oil', 'high oleic canola oil', 'soybean oil', 'high linoleic safflower oil', 'coconut oil', 'traditional canola oil', 'safflower oil']

traditional canola oil
high oleic canola oil
soybean oil
high linoleic safflower oil
coconut oil
traditional canola oil
safflower oil


Phase 3 Gene Therapy for Painful Diabetic Neuropathy

Summary: The purpose of this study is to determine the safety and efficacy of bilateral intramuscular injections of VM202 versus placebo in the treatment of painful diabetic peripheral neuropathy.~A total of 507 of 477 planned participants were randomized in a 2:1 ratio to one of two treatment groups. Note that 500 participants received IP treatment, whereas 7 participants did not receive IP treatment.~Treatments - Engensis (VM202) - 336 Engensis of 318 planned participants~Control - Placebo (VM202 vehicle) - 164 Placebo of 159 planned participants~Randomization were stratified by current use of gabapentin and/or pregabalin.
Inclusion criteria: inclusion criteria:

 Age ≥ 18 years to ≤ 75 years

 Documented history of type I or II diabetes with current treatment control (HbA1c of ≤ 10.0% at Screening) and currently on medication for diabetes (oral, injectable, and/or insulin)

 No significant changes anticipated in diabetes medication regimen

 No new symptoms associated with diabetes within the last 3 months prior to study entry

 Diagnosis of painful diabetic peripheral neuropathy in both lower extremities

 Lower extremity pain for at least 6 months

 Visual analog scale (VAS) score of ≥ 40 mm at Initial Screening (0 mm = no pain - 100 mm very severe pain)

 Symptoms from the Brief Pain Neuropathy Screening (BPNS) is ≤ 5 point difference between legs at Initial Screening

 The average daily pain intensity score of the Daily Pain and Sleep Interference Diary completed after medication wash-out is ≥ 4 with a standard deviation ≤ 2

 The physical examination component of the Michigan Neuropathy Screening Instrument Score (MNSI) is ≥ 3 at Screening

 Subjects on gabapentin (Neurontin), pregabalin (Lyrica), duloxetine (Cymbalta) for painful DPN at study entry must be on stable regimen of these treatments for at least 3 months prior to study entry

 If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study

Exclusion criteria: :

 Peripheral neuropathy caused by condition other than diabetes

 Other pain more severe than neuropathic pain that would prevent assessment of DPN

 Progressive or degenerative neurological disorder

 Myopathy

 Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease)

 Active infection

 Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis)

 Positive HIV or HTLV at Screening

 Active Hepatitis B or C as determined by Hepatitis B core antibody (HBcAb), antibody to Hepatitis B surface antigen (IgG and IgM; HBsAb), Hepatitis B surface antigen (HBsAg), and Hepatitis C antibodies (Anti HCV) at Screening

 Subjects with known immunosuppression or currently receiving immunosuppressive drugs, chemotherapy, or radiation therapy

 Stroke or myocardial infarction within last 3 months

 Specific laboratory values at Screening including: Hemoglobin < 8.0 g/dL, WBC < 3,000 cells per microliter, platelet count <75,000/mm3, Creatinine > 2.0 mg/dL; AST and/or ALT > 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary

 Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination

 Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) > 200 mmHg or diastolic BP (DBP) > 110 mmHg at Screening

 Subjects with a recent history (< 5 years) of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence for one year); subjects with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings

 Use of the following drugs / therapeutics is prohibited. Subjects may participate in the study if they are willing to discontinue use of these drugs / therapeutics 7 days prior to starting the 7 Day Daily Pain and Sleep Interference Diary. Subjects must refrain from taking these drugs or undergoing these therapies for the duration of the study

 skeletal muscle relaxants, opioids, benzodiazepines (except for stable bedtime dose),

 capsaicin, local anesthetic creams (except for lidocaine cream prior to IM injection) and patches, isosorbide dinitrate (ISDN) spray,

 transcutaneous electrical nerve stimulation (TENS), acupuncture

 If not using gabapentin (Neurontin) or pregabalin (Lyrica), subjects must agree not to start these drugs for the first 180 days of the study. Subjects on these medications at study entry must maintain a stable dose until Day 180 of the study;

 If not using duloxetine (Cymbalta), any antidepressants (e.g., amitriptyline and venlafaxine), any other antiepileptics (e.g., valproic acid, carbamazepine, vigabatrin), subjects must agree not to start these drugs for the first 6 months of the study.

 Subjects on these medications at study entry must maintain a stable dose until Day 180 of the study

 Subjects requiring > 81 mg daily of acetylsalicylic acid; subjects may be enrolled if willing/able to switch to ≤ 81 mg daily of acetylsalicylic acid or to another medication

 Subjects requiring regular COX-2 inhibitor drug(s) or non-specific COX-1/COX-2 inhibiting drugs, or high dose steroids (except inhaled steroids or ocular steroids) subjects may be enrolled if willing/able to undergo medication wash-out prior to the first dosing and to refrain from taking these drugs until Day 180 of the study

 Major psychiatric disorder within the last 180 days that would interfere with study participation

 Body mass index (BMI) > 45 kg/m2 at Screening

 Any lower extremity amputation due to diabetic complications

 Use of an investigational drug or treatment in past 6 months, or prior participation in any study of Engensis (VM202)

 Unable or unwilling to give informed consent

['Painful Diabetic Neuropathy', 'Diabetic Neuropathy, Painful']

Painful Diabetic Neuropathy
Diabetic Neuropathy
Painful


Preventing Pneumonia and Other Respiratory Problems in Persons With Spinal Cord Injury

Summary: It is known that individuals with spinal cord injury are at increased risk for respiratory tract infections like pneumonia. Part of this risk is due to weakened chest and abdominal muscles that are vital to deep breathing and the ability to cough. The purpose of this study is to look at the effectiveness of two different treatments in preventing pneumonia and other respiratory problems in persons with SCI.~This is a randomized controlled trial investigating the effectiveness of two different treatments. Participants will be randomly assigned to one of the two treatment groups. They will not be told the details of the other intervention since this could influence or change their activities during the study.
Inclusion criteria: inclusion criteria:

 Chronic spinal cord injury that occurred more than 6 months ago

 An impaired ability to cough (cough peak flow less than 300 L/min)

 Oxygen saturation greater than or equal to 95% when awake and not receiving supplemental oxygen

 End-tidal carbon dioxide level less than 43 mm Hg

 Without a fever or other signs of an acute illness for the previous 2 weeks

 Able to learn the treatment protocol and have someone available at home to assist if needed to help set-up and use the equipment

Exclusion criteria: :

 Under 18 years of age

 Currently have a tracheotomy tube

 Have a history of an acute illness in the last 2 weeks

 Have lung disease as seen on chest x-ray that results in a baseline oxygen saturation decreasing below 95% during daytime hours and cannot be normalized by usual way of coughing

 Already utilizing an oximetry protocol

 Have a significant medical complication and psychiatric condition that would interfere with the conduct of the study or interpretation of the study results.

['Manual and mechanical assisted cough', 'Incentive spirometry']

Manual and mechanical assisted cough
Incentive spirometry


Improvement of Appendix Identification and Appendicitis Diagnosis in us After Administration of Oral Contrast Medium

Summary: Rate of appendix localization on ultrasound is not high. We suggest a way to improve it's localization by oral administration of iodinated contrast material.
Inclusion criteria: inclusion criteria:

 patients in emergency department with right lower quadrant pain

Exclusion criteria: :

 patients under 18 years old

 pregnant women


Neurocognitive Robot-assisted Rehabilitation of Hand Function After Stroke

Summary: The aim of this project is to clinically evaluate a novel robot-assisted therapeutic approach to train sensorimotor hand function after stroke. It combines the profound experience of the clinic Hildebrand in neurocognitive therapy - involving brain and mind in the task and training both the motor and the sensory system - with the advanced haptic robotic technology of the Rehabilitation Engineering Lab at the Swiss Federal Institute of Technology Zurich (ETH Zurich), allowing unmet interaction with the hand through the simulation of virtual objects with various mechanical properties. In a randomized controlled clinical trial, 10 sub-acute stroke patients will receive four weeks of robotic therapy sessions, integrated seamlessly into their daily rehabilitation program, while 10 other patients will receive conventional therapy. The investigators will assess baseline performance in an initial clinical and robotic assessment, with another assessment at the end of the four-week period, and in follow-ups four weeks and six months later. The contents of the patient-tailored robotic therapy sessions will match those of the conventional therapy as closely as possible. This study will demonstrate the feasibility of including robotic therapy of hand function into the daily rehabilitation program, and investigate the acceptance from patients and therapists. The investigators expect increased training intensity during the robotic therapy session compared to conventional sessions with similar contents, as well as novel insights into the recovery process of both the motor and the sensory system during the four weeks of therapy, through advanced robotic assessments integrated into the training sessions. This project is a first step towards making such robotic therapy available to patients as integration into the conventional individual therapy program (e.g. for self-training), and towards transferring this technology to the home environment.
Inclusion criteria: inclusion criteria:

 age between 18-90 years old

 hemisyndrome (central paralysis of the upper extremity, and all degrees of weakness: M0 - M5 on the paresis scale) as a result of a first stroke

 sub-acute lesion not more than 6 weeks post ictus

Exclusion criteria: :

 insufficient state of consciousness

 severe aphasia

 severe cognitive deficits

 severe pathologies of the upper extremity of traumatic or rheumatic nature

 severe pain in the affected arm

 Patients with pacemakers and other active implants

['robot-assisted neurocognitive therapy of hand function', 'Conventional neurocognitive rehabilitation']


Immunization With Different Doses of Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis

Summary: Malaria is one of the major infectious diseases in the world with a tremendous impact on the quality of life significantly contributing to the ongoing poverty in endemic countries. It causes almost one million deaths per year, the majority of which are children under the age of five. The malaria parasite enters the human body through the skin, by the bite of an infected mosquito. Subsequently, it invades the liver and develops and multiplies inside the hepatocytes. After a week, the hepatocytes burst open and the parasites are released in the blood stream, causing the clinical phase of the disease.~As a unique opportunity to study malaria immunology and efficacy of immunisation strategies, a protocol has been developed in the past to conduct experimental human malaria infections (EHMIs). EHMIs generally involve small groups of malaria-naïve volunteers infected via the bites of P. falciparum infected laboratory-reared Anopheline mosquitoes. Although potentially serious or even lethal, P. falciparum malaria can be radically cured at the earliest stages of blood infection where risks of complications are virtually absent.~The investigators have shown previously that healthy human volunteers can be protected from a malaria mosquito (sporozoite) challenge by immunization with sporozoites (by mosquito bites) under chloroquine prophylaxis (CPS immunization). However, it is unknown how many mosquito bites are necessary to confer protection. Moreover, as all volunteers were protected in this study, no correlates of protection could be established. For future development of vaccines and understanding of protective immunity to malaria, it is important to investigate the lowest dose of CPS immunization that confers 100% protection and to find correlates of protection. Therefore, the present study aims to make the CPS immunization protocol more sensitive by lowering the number of infected mosquito bites, in order to study the underlying mechanisms of protection.
Inclusion criteria: inclusion criteria:

 Age > 18 and < 35 years healthy volunteers (males or females)

 Good health based on history and clinical examination

 Negative pregnancy test

 Use of adequate contraception for females

 All volunteers must sign the informed consent form demonstrating their understanding of the meaning and procedures of the study

 Volunteer agrees to inform the general practitioner and agrees to sign a request to release medical information concerning contra-indications for participation in the study

 Willingness to undergo a Pf mosquito challenge

 For volunteers not living in Leiden: agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 after challenge till 3 days after treatment)

 Reachable (24/7) by mobile phone during the whole study period

 Living with a third party that could contact the clinicians in case of alteration of consciousness or agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 after challenge till 3 days after treatment)

 Available to attend all study visits

 Agreement to refrain from blood donation to Sanquin or for other purposes, during the study period until 337.

 Willingness to undergo HIV, hepatitis B and hepatitis C tests

 Negative urine toxicology screening test at screening visit and day before challenge

 Willingness to take a prophylactic regime of chloroquine and curative regimen of Malarone®

Exclusion criteria: :

 History of malaria

 Plans to travel to malaria endemic areas during the study period

 Plans to travel outside of the Netherlands during the challenge period

 Previous participation in any malaria vaccine study and/or positive serology for Pf

 Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers

 History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)

 History of arrhythmias or prolonged QT-interval

 Positive family history in 1st and 2nd degree relatives for cardiac disease < 50 years old

 An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system

 Clinically significant abnormalities in electrocardiogram (ECG) at screening

 Body Mass Index (BMI) below 18 or above 30 kg/m2

 Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis

 Positive HIV, HBV or HCV tests

 Participation in any other clinical study within 30 days prior to the onset of the study

 Enrollment in any other clinical study during the study period

 Pregnant or lactating women

 Volunteers unable to give written informed consent

 Volunteers unable to be closely followed for social, geographic or psychological reasons

 Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study

 A history of psychiatric disease

 Known hypersensitivity to Malarone® or chloroquine

 The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period

 Contra-indications to Malarone® or chloroquine including treatment taken by the volunteer that interferes with Malarone® or chloroquine

 Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia

 Co-workers of the departments of Medical Microbiology, Parasitology, or Internal Medicine of the Leiden University medical Centre

 A history of sickle cell anemia, sickle cell trait, thalassemia, thalassemia trait or G6PD deficiency

['Chloroquine prophylaxis', 'Immunization', 'Plasmodium falciparum challenge', 'Malarone treatment']

Chloroquine prophylaxis
Immunization
Plasmodium falciparum challenge
Malarone treatment


The Effect of Intravenous Lidocaine on Pain After Lumbar Spinal Fusion

Summary: This prospective randomized study aims to evaluate the effectiveness of intravenous lidocaine injection on the relief of pain in patients undergoing 1-level posterior lumbar fusion.~A total of 54 patients will be randomized into one of two groups (group C or group I) based on Excel number generation.~Patients in group C will receive received normal saline intravenous injection, and patients in group I will receive an intravenous bolus injection of 1.5 mg/kg lidocaine followed by a continuous lidocaine infusion of 2 mg/kg/hr.~Visual analogue scale pain scores, fentanyl consumption and the frequency at which patients pushed the button (FPB) of a patient-controlled analgesia system will be recorded at 4, 12, 24, 48 hours postoperatively.
Inclusion criteria: inclusion criteria:

 1-level posterior lumbar fusion

Exclusion criteria: :

 mental change

 allergy to local anesthetics

 chronic analgesics user

['Intravenous lidocaine injection', 'Intravenous normal saline injection']

Intravenous lidocaine injection
Intravenous normal saline injection


Neuromuscular Electrical Stimulation (NMES) Treatment Technique Therapy in the Management of Young Infants With Severe Dysphagia

Summary: The goal of this study is to obtain data that well help inform the feasibility and design of a randomized control trial of the therapeutic Neuromuscular Electrical Stimulation (NMES) technique in improving the swallowing function of young infants presenting with severe dysphagia.
Inclusion criteria: inclusion criteria:

 Infants with severe dysphagia on VFFS as defined by dysphagia resulting in aspiration with swallow of at least 2 food textures (e.g. thin and thick liquid).

 We will include children with dysphagia due to a central neurologic deficit. The neurologic diagnosis will be based on the diagnosis from the treating physician.

Exclusion criteria: :

 Infants with a known or suspected neurodegenerative or peripheral neuromuscular condition or a medical condition that is a contraindication for NMES treatment (tumours in the neck region and neck soft tissue infections).

 Children with neurodegenerative disorders have been excluded as their natural history of dysphagia would be different from those with a static neurologic disorder.

['Neuromuscular electrical stimulation (NMES)']


Is it Effective to Treat Patients With Blastocystis Hominis Infection?

Summary: The objective of this study is to determine whether in the setting of primary health care it is effective to treat with metronidazole returning travellers with gastrointestinal symptoms and B. hominis in the stool or not.
Inclusion criteria: inclusion criteria:

 ≥ 18 years

 Gastrointestinal symptoms for more than 10 days

 B. hominis in any quantity in at least one stool specimen out of 3 examined

 No other pathogenic micro-organism identified

Exclusion criteria: :

 Fever > 37.5°

 bloody diarrhoea

 weight loss > 10% of usual body weight

 significant decrease of general condition

 oncological diseases

 immune deficiencies

 known chronic intestinal diseases

 use of anti-protozoan drugs in the last 2 weeks

 use of anti-coagulant treatment or antabuse

 pregnant and lactating women


Regional Cortical Cerebral Quantitative MRI Perfusion Correlation Neurocognition in Multiple Sclerosis

Summary: Multiple Sclerosis (MS) is a common disease affecting 1/1000 Canadians. Cognition impairment is reported in 40-65% of patients and is socially and functionally disabling. Although multiple sclerosis is widely regarded as a white matter disease, cortical disease burden is increasingly emphasized. Studies confirm that gray matter (GM) disease is grossly underestimated by conventional MRI. Although the cause for MS is unknown vascular impairment is implicated in nerve cell death. Several studies have shown perfusion abnormalities in the central GM and white matter (WM) structure. Severity of perfusion reduction correlates with lesion load, atrophy, MS subtype and disease duration. Further extent of cortical atrophy correlates with neurocognitive impairment. We hypothesize that cortical perfusion is a marker of cortical disease severity and correlates with neurocognitive impairment. To show this we will measure regional cortical perfusion and regional brain and WM lesion volumes in 26 predefined brain regions using a template developed for Alzheimer's disease. Regional perfusion will be correlated with neurocognitive tests validated for MS use. Patients will be divided into impaired and non impaired and perfusion compared controlling for known confounding factors. If confirmed cortical perfusion may be utilized as a surrogate marker of cognitive outcome in therapeutic studies.
Inclusion criteria: inclusion criteria:

 established SPMS according to the McDonald criteria

Exclusion criteria: :

 Patients with a history of drug/alcohol abuse, a premorbid (pre MS) psychiatric history, a head injury with loss of consciousness and a concurrent physical disease requiring medical attention (eg. cardiovascular disease etc), MRI contraindication including implants, pacemaker, aneurysm clips and known renal impairment


Intestinal Barrier Function and Probiotics.

Summary: Rationale: Enterotoxigenic Escherichia coli (ETEC) bacteria adhere to the mucosa of the proximal intestines. There it produces an toxin which presents a local and relevant challenge to the intestines. This is proposed to give an indication of general resistance and/or the local resistance of the intestines. The sequel of events of mucosal inflammation will be characterized in this study. In addition we will evaluate the effects of probiotics by comparing the infection symptoms and by measuring faecal weight and mucus in faeces.~Objective: The main objective of this study is to investigate the effect of probiotics on the sequels of ETEC administration as intestinal permeability, inflammation and clinical signs as total faecal output, relative faecal dry weight and mucin excretion in faeces. In addition, the sequels of the mucosal inflammation will be characterized and biomarkers will be searched.
Inclusion criteria: inclusion criteria:

 Healthy as assessed by the

 health and lifestyle questionnaire, (P9067 F02; in Dutch)

 physical examination

 results of the pre-study laboratory tests

 Males, Age >= 21 and <= 40 years at Day 01 of the study

 Body Mass Index (BMI) >= 20 and < 33 kg/m2. Preferably in high and low body fat mass ranges as to be determined by waist circumference

 Normal Dutch eating habits as assessed by P9067 F02

 Voluntary participation

 Having given written informed consent

 Willing to comply with the study procedures, including the ETEC challenge

 Willing to accept use of all nameless data, including publication, and the confidential use and storage of all data for at least 15 years

 Willing to accept the disclosure of the financial benefit of participation in the study to the authorities concerned.

Exclusion criteria: :

 Subjects with one or more of the following characteristics will be excluded from participation:

 Participation in any clinical trial including blood sampling and/or administration of substances up to 90 days before Day 01 of this study

 Participation in any non-invasive clinical trial up to 30 days before Day 01 of this study, including no blood sampling and/or oral, intravenous, inhalatory administration of substances

 Having a history of medical or surgical events that may significantly affect the study outcome, including gastrointestinal illness or surgical operations,

 Use of antibiotics, immunosuppressive drugs, antacids, laxatives or anti-diarrhoeal drugs in the last 3 months before the study

 Alcohol consumption > 28 units/week for males

 Reported unexplained weight loss or gain of > 2 kg in the month prior to the pre-study screening

 Reported slimming or medically prescribed diet

 Reported vegan, vegetarian or macrobiotic

 Not willing to be off working as a food handler, in child care or as a healthcare worker with direct patient contact during the week of ETEC contamination

 Not willing to give up blood donation during the study.

 Personnel of TNO Quality of Life, their partner and their first and second degree relatives

 Not having a general practitioner

 Not willing to accept information-transfer concerning participation in the study, or information regarding his/her health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner.

['Intestinal Permeability', 'Challenge Test', 'Intestinal Health', 'Inflammation']

Intestinal Permeability
Challenge Test
Intestinal Health
Inflammation


Evaluation of the Clinical Effectiveness of a Collagen-ORC Antimicrobial Matrix in Full-Thickness, Neuropathic Diabetic Foot Ulcers

Summary: This is a randomized (1:1), prospective, open label, multicenter, comparative study to be examine the effectiveness of Collagen-ORC Antimicrobial matrix, a new wound dressing, on diabetic foot ulcers.
Inclusion criteria: inclusion criteria:

 18 years of age or older.

 Ambulatory (i.e. walking is the primary method of mobilization. Crutches, walker, walking frame or other ambulation aids are permitted).

 Diagnosed Type 2 diabetic (i.e. not juvenile onset).

 Have a DFU on the plantar surface of either foot.

 Have a DFU of >4 wks but <6 months duration.

 Willing and capable of cooperating to the extent and degree required by the study protocol

Exclusion criteria: :

 Be < 1cm2 or >10cm2 in area, by planimetry.

 Demonstrate overt signs of infection.

 Be located on the dorsal, lateral, or posterior heel area of the foot (Change 2, Amendment 1).

 Have visible exposed bone or tendon.

 Have an adjacent thermal injury or wound of an etiology other than diabetes.

 Be within 5 cm of any other wound, regardless of etiology.

 Have received enzymatic debriding agents in the past 7 days.

 Have received topical antibiotic therapy in the past 7 days.

 Be less than 1 cm2 or exceed 10cm2 in area by planimetry, after debridement.

 Have exposed bone or tendon, after debridement

 The study subject MUST NOT:

 Have received previous treatment for the study ulcer by this Investigator.

 Have more than 3 full thickness ulcers, in total.

 Be pregnant or nursing an infant

 Have a concurrent illness or condition which may interfere with wound healing, such as carcinoma, vasculitis, immune system disorders or connective tissue disorder.

 Be a known alcohol or drug abuser.

 Have received systemic corticosteroids, immunosuppressive or chemotherapeutic agents in the past 30 days.

 Have received radiotherapy, which includes the lower extremity, at any time.

 Have a marked Charcot foot or claw foot deformity which would limit the ability of the subject to wear or be compliant with the wearing of the standardized off-loading device used in this study.

 Have received an investigational drug or device in the past 30 days.

 Have a known hypersensitivity to bovine collagen, oxidized regenerated cellulose (ORC) or silver.

 Be unwilling or unable to be fitted or compliant with the wearing of an ulcer off-loading device.

 Known to be non-compliant or unlikely to complete the study.

 Have ABPI < 0.7, OR, if ABPI >1.0 and toe pressure >0.6.

 Have serum Creatinine > 3 mg/dL25. have Hgb A1C>9%

['Collagen ORC Antimicrobial Matrix (CAM)']


Safety and Feasibility Study of a Mechanical Ventilation Computerized Protocol: Intellivent

Summary: The present protocol will demonstrate the safety, feasibility and efficacy of a newly computerized protocol integrated into a ventilator: S1 ventilator (Hamilton Medical). During ventilation with S1 ventilator, the respiratory support including oxygenation and CO2 removal parameters are continuously adapted to patient respiratory status using science based rules. The present protocol is designed as a pilot evaluative study where the researchers will evaluate the safety, feasibility and efficacy of ventilating children during the weaning phase with the S1 ventilator for 5 hours, and compare to conventional ventilation.
Inclusion criteria: inclusion criteria:

 An eligible subject will be considered for inclusion into this clinical trial if the attending physician is ready to begin weaning from mechanical ventilation and if the patient fulfils all the following inclusion criteria:

 The attending physician thinks that the patient will be able to breathe spontaneously or the patient is already breathing spontaneously.

 No vasopressor or inotropic medication, unless the patient is receiving some digitalin or small doses of dopamine or dobutamine (≤ 5 µg/kg/min)

 Slight or no endotracheal tube gas-leakage ((Vti - Vte)/Vti ≤ 20%)

 Mechanical ventilation with a plateau pressure ≤ 25 cmH2O over PEEP

 PEEP ≤ 8 cmH2O

 FiO2 ≤ 60% in order to obtain pulse oxymetry ≥ 95%

 PaCO2 < 70 mmHg on the last blood gases

 Extubation not expected the day of inclusion

 Gap between ETPCO2 and PCO2 < 7 mmHg on last blood gas.

Exclusion criteria: :

 A patient will be excluded from this study a priori if he/she presents one or many of the following criteria:

 The patient fails the pressure-support test (this test is described below in the section entitled Intervention).

 Invasive or non invasive mechanical ventilation at home or on hospital ward before PICU admission.

 Child with a tracheotomy

 Child with an history of mechanical ventilation > 2 months

 Contemplate withdrawing mechanical ventilation for palliative care

 Child with tracheobronchomalacia responsible for chronic respiratory failure

 Child with a severe neuromuscular disease prior to admission or acquired in the PICU and unable to generate a negative pressure of at least - 20 cmH20 during inspiration.

 Child with a do not resuscitate order and/or do not reintubate order is prescribed

 The child is still receiving some curare

 Cyanotic congenital heart disease with unrepaired or palliated right to left intracardiac shunt.

 Primary pulmonary hypertension.

 Child not expected to survive within a week, according to the attending intensivist

 Brain death or suspected brain death

 Morbid obesity defined by a body mass index (Actual Body Weight/T² > 40)

 Pregnant patient

 Parents or tutors do not agree to sign the consent form

 S1 ventilator is not available

 SpO2 monitoring not available (no plethysmographic curve) or not reliable

 EtCO2 not available (no capnogram) or no reliable (see above gap)

['Mechanical Ventilation Weaning Phase in Children']


A Trial to Evaluate the Efficacy of Low Dose Vaginal Estrogens in the Treatment of Atrophic Vaginitis

Summary: Atrophic vaginitis is a common problem that occurs in up to 40% of postmenopausal women. The main symptoms are dryness, itching and burning in and around the vagina. These symptoms in turn can cause pain with intercourse. Other symptoms can include urinary frequency and urinary urgency. These symptoms are caused by the decreasing levels of estrogens in postmenopausal women.~The current treatment options include hormone replacement therapy by mouth and patch and vaginal creams, tablets and rings. The current guideline recommend using hormone therapy at the lowest dose for the shortest time. We are trying to find the lowest effective dose of estrogen cream that helps with symptoms without causing an increase in estrogens in the blood stream.~We want to compare two estrogen creams, estradiol and estriol, each at very low doses, with a placebo cream. Estradiol cream is available on prescription but we want to see how effective it is at one tenth the commonly prescribed dose. Estriol cream is not commonly prescribed and is only available at compounding pharmacies. We want to see if either of these estrogens is effective at one tenth the usual dose. We also want to see if these creams are effective when massaged onto the outer part of the vagina, rather than the usual method of treatment, which is inserting them into the vagina.
Inclusion criteria: inclusion criteria:

 Postmenopausal women (no menses for the previous 12 months)

 Dryness, itching or burning in and around the vagina

 Discontinued hormone replacement therapy (either local or systemic) at least 3 months

Exclusion criteria: :

 Known, suspected, or history of cancer of the breast.

 Known, or suspected estrogen dependent neoplasia (ovarian, endometrial).

 Known hypersensitivity to any component of the medications or base creams.

 Active deep vein thrombosis, pulmonary embolism, or history of these conditions.

 Active or recent (within the past year) arterial thromboembolic disease (stroke, myocardial infarct).

 Liver dysfunction or disease with elevation of aspartate aminotransferase (AST)>1.5x upper level of normal (ULN); Normal for females is 8-43 U/L.

 Undiagnosed abnormal genital bleeding.

 Known chronic lichen sclerosis.

 Known, untreated vaginal infection.

 Not had a normal screening mammogram within the last 15 months.

 Hysterectomy without oophorectomy unless 60 years or older.

 Women taking aromatase inhibitors or tamoxifen.

 Hgb <12.0 or >15.5 g/dL

 Urinalysis showing a urinary tract infection (UTI).

['Estriol', 'Estradiol valerate', 'Vanicream Lite']

Estriol
Estradiol valerate
Vanicream Lite


Evaluation of the Discontinuation of Maintenance Corticosteroid Treatment in Quiescent Systemic Lupus

Summary: Systemic Lupus (SLE) is a chronic disease for which long term treatments are warranted. The aim of this study was to study the possibility of corticosteroids interruption in patients with quiescent SLE treated since at least one year with 5 milligrams of predonisone per day.
Inclusion criteria: inclusion criteria:

 Patients with SLE according to the ACR revised criteria.

 Quiescent disease without flare since at least one year (SELENA SLEDAI < or equal to 4, BILAG C, D or E, PGA 0) _ Treatment with 5 milligrams/day of prednisone since at least 1 year

Exclusion criteria: :

 failure to sign the informed consent or unable to consent

 Patient participating to another clinical trial

 Pregnancy or plan to become pregnant


A Long-Term Safety And Tolerability Study Of Bapineuzumab In Alzheimer Disease Patients

Summary: The purpose of this study is to assess the long-term safety and tolerability of bapineuzumab in subjects with Alzheimer Disease who participated in study 3133K1-3000 (NCT00667810). Over 250 sites will participate in over 26 countries. Subjects will receive bapineuzumab. Each subject's participation will last approximately 4 years.
Inclusion criteria: inclusion criteria:

 Subject has completed study 3133K1-3000 and brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of Alzheimer Disease

 Mini-Mental Status Examination (MMSE) >=10 at screening

 Caregiver able to attend all clinic visits with subject

Exclusion criteria: :

 Any medical or psychiatric contraindication or clinically significant abnormality that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response.

 Any significant brain MRI abnormality.

 Use of any investigational drugs or devices, other than bapineuzumab within the last 60 days prior to screening

['Bapineuzumab 0.5 mg/kg', 'Bapineuzumab 1.0 m/kg']

Bapineuzumab 0.5 mg/kg
Bapineuzumab 1.0 m/kg