A Study to Evaluate the Effects of a Natural Supplement in Adults With Chronic Functional Constipation

Summary: Constipation is common in the general population, especially in women and in the elderly. Hard stool is a complaint often associated with constipation, which suggests that stool softening would provide a major benefit in the strategy of treatment.~This investigative fibre product is primarily a soluble dietary fibre with added probiotics and a prebiotic. It is not digested in the small intestine and partly remains undigested by bacteria in the gut. Also, as probiotics are believed to help restore a healthy gut flora, reduce pH, assist with digestion of food and reduce gaseous by-products they may aid the improvement of intestinal motility.~The objective of this study is to assess if this investigative, fibre product effects the number of bowel movements per week and if this in turn impacts quality of life and symptoms of constipation.
Inclusion criteria: inclusion criteria:

 To be considered eligible for enrolment into the study, subjects must;

 Be able to give written informed consent,

 Be between 18 and 80 years of age,

 Subject has chronic functional constipation according to the Rome III Diagnostic Criteria, where (f) is mandatory.

 i. Must include two or more of the following:

 Straining during at least 25% of defæcations

 Lumpy or hard stools in at least 25% of defæcations

 Sensation of incomplete evacuation for at least 25% of defæcations

 Sensation of anorectal obstruction / blockage for at least 25% of defaecations

 Manual manœuvers to facilitate at least 25% of defæcations (e.g., digital evacuation, support of the pelvic floor)

 Fewer than 3 defæcations per week ii. Loose stools are rarely present without the use of laxatives iii. Insufficient criteria for irritable bowel syndrome * Criteria fulfilled for the last 3 months, with symptom onset at least 6 months prior to diagnosis

 Subjects will continue on his/her normal diet,

 The subject agrees to complete the Patient Diary for two weeks prior to study entry and for the duration of the study.

Exclusion criteria: :

 Subjects will be excluded from the study if they meet any of the below criteria;

 Are less than 18 and greater than 80 years of age,

 Females are pregnant, lactating or wish to become pregnant during the study.

 Are hypersensitive to any of the components of the test product,

 Have a significant acute or chronic, unstable and untreated disease or any condition which contraindicates, in the investigators judgement, entry to the study,

 Subject has an obstructive or metabolic aetiology for constipation,

 Subject has a history of laxative abuse (greater than the daily dosage recommended on the label for any laxative),

 Subject has used a probiotic or prebiotic product or a dietary fibre supplement in the 4 weeks prior to the baseline visit,

 Subject has a history of drug and/or alcohol abuse at the time of enrolment

 Having a condition or have taken a medication that the investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results;

 Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial,

 Subjects may not be receiving treatment involving experimental drugs,

 If the subject has been in a recent experimental trial, these must have been completed not less than 90 days prior to this study.

 Have a malignant disease or any concomitant end-stage organ disease


Epidemiology of Chronic Bronchitis in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Summary: The purpose of this study was to investigate the prevalence of chronic bronchitis in patients suffering from moderate to very severe chronic obstructive pulmonary disease (COPD), and to assess the difference in exacerbation rates in patients suffering from moderate to very severe COPD with chronic bronchitis vs. a population of patients without chronic bronchitis.
Inclusion criteria: inclusion criteria:

 1. Written informed consent. 2. Age ≥ 40 years. 3. Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) ratio (post-bronchodilator) <70%. 4. FEV1 (post-bronchodilator) < 80% of predicted.

Exclusion criteria: :

 1. Moderate and severe exacerbations during the last 4 weeks. 2. Pregnancy. 3. Already participated in the study (allowed to participate only once).

['Chronic Obstructive Pulmonary Disease', 'Chronic Bronchitis']

Chronic Obstructive Pulmonary Disease
Chronic Bronchitis


Resolution Endoclips Vs Epinephrine Injection and Heater Probe

Summary: To compare the efficacy of a novel endoscopic clipping device(Resolution Clip™) and conventional epinephrine injection and heater probe thermocoagulation in control of peptic ulcer bleeding and prevention of recurrent bleeding
Inclusion criteria: inclusion criteria:

 Age >16 , can obtain written consent

 Ulcers that require endoscopic therapy with SRH: Forrest I a, Ib, II a and II b

Exclusion criteria: :

 Moribund patients with terminal malignancy

 Pregnancy

 Intercurrent ulcer complication that prevents treatment and surgery becomes mandatory such as bulbar stenosis and ulcer perforation

['Resolution clip (endo-clipping device)']


A Study of Inhalation of 20,000 EU CCRE in Normal Volunteers Compared to Allergic Asthmatic Individuals

Summary: This will be a single center, open label study comparing baseline characteristics of recovered sputum cells (collected on screening day) to those of cells recovered 6 hours after inhalational challenge with 20,000 EU Clinical Center Reference Endotoxin (CCRE, a component of air pollution)) within each group as well as cross group comparisons between individuals with allergic asthma (AA's)and normal volunteers (NV's). The primary objective of this study is to test the hypothesis that persons with allergic asthma will have an increased neutrophil response to challenge with 20,000 EU CCRE compared to normal volunteers. Secondary objectives include post CCRE comparison between AA's and NV's with regard to changes in airway cells and blood as well as changes in mucociliary clearance (MCC) in response to inhalation of 20,000 EU CCRE.
Inclusion criteria: inclusion criteria for healthy controls:

 Normal lung function, defined as (Knudson 1976/1984 predicted set):

 FVC of > 80 % of that predicted for gender, ethnicity, age and height FEV1 of > 80 % of that predicted for gender, ethnicity, age and height FEV1/FVC ratio of > .75

 Oxygen saturation of > 94 % and normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)

 Symptom Score no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score.

 Negative methacholine inhalation challenge as performed in the screening protocol. (Less than a 20% decrease in FEV1 at a maximum methacholine concentration of 10 mg/ml)

 --Negative pregnancy test for females

 Negative allergy skin test (AST)

 inclusion criteria for allergic asthmatics also include:

 History of episodic wheezing, chest tightness, or shortness of breath after age of 6 years consistent with asthma, or physician diagnosed asthma after age of 6 years.

 Positive methacholine test.

 FEV1 of at least 80% of predicted and FEV1/FVC ratio of at least .70 (without use of bronchodilating medications for 12 hours)

 Allergic sensitization to at least one of the following allergen preparations: (House Dust Mite f, House dust mite p, Cockroach, Tree mix, Grass Mix, Weed Mix, Mold Mix 1, Mold Mix 2, Rat, Mouse, Guinea Pig, Rabbit, Cat or Dog) confirmed by positive AST.

 Negative allergy skin test as performed in the screening protocol.

Exclusion criteria: :

 Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, or chronic thyroid disease.

 Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.

 Use of systemic steroid therapy within the preceding 12 months for an asthma exacerbation. All use of systemic steroids in the last year will be reviewed by a study physician.

 Use of inhaled steroids, cromolyn or leukotriene inhibitors (montelukast or zafirlukast) except for use of cromolyn exclusively prior to exercise.

 Use of daily theophylline within the past month.

 Use of tricyclics and MAO inhibitors

 Pregnancy or nursing a baby.

 Cigarette smoking > 1 pack per month.

 Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.

 Exacerbation of asthma more than 2x/week which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.

 Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).

 Viral upper respiratory tract infection within 2 weeks of challenge.

 Any acute infection requiring antibiotics within 2 weeks of challenge

 Receipt of LAIV (Live Attenuated Influenza Vaccine), also know as FluMist®, within the prior 14 days

['Clinical Center Reference Endotoxin (CCRE)', 'Clinical Center Reference Endotoxin (CCRE)']


A Study to Evaluate MK0476 and Fluticasone to Control Asthma in Patients With Mild Persistent Asthma (0476-910)

Summary: A study to evaluate MK0476 and Fluticasone to control asthma in patients with mild persistent asthma.
Inclusion criteria: inclusion criteria:

 Patient is male or female, 6-14 years of age with mild persistent asthma

 Patient has a history of the following symptoms: wheezing, chest tightness, cough, etc.

 Patient has asthma diagnosed by a doctor

Exclusion criteria: :

 Patient is hospitalized

 Patient has had major surgery or participated in another clinical trial in the last 4 weeks

 Patient has been on a breathing tube for asthma

['MK0476, montelukast sodium / Duration of Treatment: 1 Year', 'Comparator : fluticasone propionate / Duration of Treatment: 1 Year']


Anti-inflammatory H1 Antihistamines Allergic Rhinitis

Summary: The main purpose of the treatment of persistent allergic rhinitis is to improve symptoms and patients' quality of life and prevent the development of asthma. Therapeutic strategies also target a reduction of pro-inflammatory mediators released from activated cells, including mast cells and epithelial cells. The presence of allergic inflammation in nasal mucosa may increase the risk of asthma occurrence, especially in patients with persistent allergic rhinitis. H1 antihistamines are widely recommended in all types of allergic rhinitis, regardless of symptom severity or persistence. They control all of the symptoms, but to a lesser extent nasal congestion. New generation agents, such as levocetirizine and desloratadine, possess anti-inflammatory properties, reducing allergic inflammation.
Inclusion criteria: inclusion criteria:

 persistent allergic rhinitis

Exclusion criteria: :

 the presence of asthma or nasal polyps,

 acute and chronic upper respiratory infections,

 administration of intranasal or systemic corticosteroids or H1 antihistamines in the past 30 days.


A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder

Summary: This study employs functional magnetic resonance imaging to compare brain activation patterns during a depressive episode in patients diagnosed with bipolar disorder, major depressive disorder, and a group of healthy control subjects. Depressed patients will be treated with a combination of fluoxetine and olanzapine and undergo MRI scans before, during, and after pharmacotherapy.
Inclusion criteria: inclusion criteria: (All three groups)

 age 18-55 years

 satisfactory physical health

 education level and a degree of understanding to communicate effectively with the investigator c

 capable of providing informed consent

 female subjects of childbearing potential, a medically accepted means of contraception.

 Additional inclusion criteria for the patient groups include

 DSM-IV-TR criteria for a diagnosis of BD or MDD

 currently meeting criteria for an MDE and

 a Hamilton Depression Rating Scale 17 Item (HDRS-17) score of > 17

 blood indices within normal clinical ranges.

Exclusion criteria: : (All three groups)

 DSM-IV-TR criteria for substance abuse or dependence (except nicotine or caffeine) within the past 6 months

 comorbid neurological or other major psychiatric disorders as defined in the DSM-IV-TR;

 history of neurological trauma resulting in loss of consciousness;

 uncorrected hypothyroidism or hyperthyroidism, including elevated thyroid stimulating hormone (TSH);

 other unstable medical condition;

 female subjects who are pregnant or nursing;

 Additional

['Fluoxetine+Olanzapine', 'Olanzapine', 'Functional Magnetic Resonance Imaging']

Fluoxetine+Olanzapine
Olanzapine
Functional Magnetic Resonance Imaging


Lung Cancer Screening Study With Low-dose CT Scan and Blood Biomarker

Summary: Lung cancer is the number one cancer killer in the USA. Early stage lung cancer is asymptomatic. Most patients with lung cancer are usually symptomatic at diagnosis and already have advanced stage disease. Low dose CT screening (LDCT) for high risk individuals has recently been shown to decrease lung cancer mortality by 20%. However, 4 out of 5 lung cancer deaths are not prevented with LDCT screening alone.
Inclusion criteria: inclusion criteria:

 Smokers or former smokers

 At least 20 pack year history of smoking

 Ages 50 - 75

Exclusion criteria: :

 Had a CT scan of chest within last 24 months

 History of any cancer within 10 yrs (except skin cancer or cervical cancer)

 A serious illness that decreases life expectancy to less than 5 years

 Any current use of Oxygen

 Uncontrolled congestive heart failure or cardiac arrhythmia that would prevent surgery for a lung lesion

 Severe COPD or dyspnea that would prevent lung surgery or stereotactic body radiotherapy

['CT scan & Early CDT Lung test', 'CT scan & Early CDT Lung test']

CT scan & Early CDT Lung test
CT scan & Early CDT Lung test


Adaptive Treatment for Alcohol and Cocaine Dependence

Summary: Primary objective #1: Determine the relative effectiveness of MI-IOP and MI-PC in the full study sample with regard to treatment engagement over weeks 1-12 and cocaine/alcohol use over weeks 1-24.~Hypothesis 1: An intervention that explores several possible treatment options with the patient and provides the chosen option (e.g., MI-PC) will produce higher rates of treatment engagement than an intervention focused on engagement in IOP only (e.g., MI-IOP).~Hypothesis 2: An intervention that explores several possible treatment options with the patient and provides the chosen option (e.g., MI-PC) will produce better cocaine/alcohol use outcomes than an intervention focused on engagement in IOP only (MI-IOP).~Secondary analysis 1: Among the Non-engaged patients, determine rates of selection of each of the three options in MI-PC, retention rates within each option, and cocaine/alcohol use outcomes in each option.~Secondary analysis 2: Among the Engaged patients, determine rates of selection of each of the three options in MI-PC, retention rates within each option, and cocaine/alcohol use outcomes in each option.~Primary objective #2: Determine whether the relative effectiveness of MI-IOP and MI-PC varies as a function of engagement group, with regard to treatment engagement over weeks 1-12 and cocaine/alcohol use outcomes over weeks 1-24.~Hypothesis 1: The predicted main effect on retention favoring MI-PC over MI-IOP will be significantly larger among patients in the Non-engaged group than among those in the Engaged group.~Hypothesis 2: The predicted main effect on cocaine/alcohol use outcomes favoring MI-PC over MI-IOP will be significantly larger among patients in the Non-engaged group than among those in the Engaged group.
Inclusion criteria: inclusion criteria:

 meet DSM-IV criteria for lifetime cocaine or alcohol dependence and have used cocaine or alcohol in the prior 6 months;

 be > 18 years of age;

 be judged clinically appropriate for IOP (e.g., no current psychotic disorder or evidence of severe dementia, and no acute medical problem requiring inpatient treatment;

 have no regular IV heroin use during the past year;

 have access to a telephone;

 be willing to be randomized and participate in research; and

 no current participation in methadone or other forms of DA treatment, other than IOP. Finally, because of study follow-up requirements, subjects will

 be required to be metropolitan area residents, and

 be able to provide the name, verified telephone number, and address of at least two contacts who can provide locator information on the patient during follow-up. We will include patients with dependence on other substances, provided that they are cocaine dependent and meet other inclusion criteria.

Exclusion criteria: :

 have a current psychotic disorder (as assessed with the psychotic screen from the MINI) or evidence of dementia severe enough to prevent participation in outpatient treatment;

 have acute medical problem requiring immediate inpatient treatment; or

 are currently participating in methadone or other forms of DA treatment, other than IOP.

['Motivational Interviewing', 'Telephone counseling', 'Cognitive Behavioral Therapy (CBT) Counseling', 'medication management', 'Intensive OutPatient Therapy']


Sputum Pharmacokinetics of TB Drugs and Bacterial Drug Resistance

Summary: Background:~Many people around the world get tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infections. Sometimes medicine that treats these infections does not get to where the bacteria are in the lungs. Researchers want to find a way to tell if enough medicine is getting to where it is needed in the lungs. They will look at how much medicine is in your sputum (what you cough up) compared to how much is in your blood. They will also investigate a new test to quickly figure out what medicines are likely to treat TB effectively.~Objective:~To determine the relationship between the concentration of TB drugs in plasma and sputum over time.~Eligibility:~People ages 18 and older who have TB or NTM infection that is suspected to be drug resistant. They must be taking TB or NTM medicines.~Design:~Participants will be screened with medical history.~Participants will be in the study for 2 8 days.~Participants will give 3 or more sputum samples over at least 2 different days. They will cough sputum into a cup.~Participants will have blood drawn 4 times a day on 2 different days.
Inclusion criteria: inclusion criteria:

 At least 18 years of age

 Diagnosis of TB (and/or NTM for NIH clinical center subjects)

 Ongoing signs and/or symptoms of pulmonary TB (and/or NTM at the NIH CC)

 Suspected drug resistance (drug susceptible allowed at the NIH CC)

 Available to provide at least 3 sputa over 2 or more days

 Taking anti-tuberculosis medicines (or NTM meds at NIH CC) during the time sputa are provided

 Thought likely to be Mycobacterium culture positive (including NTM infected for the NIH CC) by enrolling physician

 GeneXpert MTB/RIF sputum TBpositive (China subjects only)

 Likely able to produce sputum samples while on study

 Willing to provide blood samples

 Willing to have samples stored

Exclusion criteria: :

 Acute liver or kidney disease

 Conditions which compromise the subject s ability to take or absorb oral drugs


Coffee Roasting and Glucose Tolerance

Summary: Chlorogenic acid (CGA) in coffee may lower the postprandial glucose response. CGA is destroyed by dark roasting. In a controlled crossover trial, 11 healthy fasted volunteers consumed 300 mL of either light (LIR) or dark (DAR) roasted coffee, or water, followed 30 min later by a 75-g oral glucose tolerance test (OGTT). Plasma glukose and insulin, appetite, and plasma and urine metabolic profiles will be analysed. The primary aim is to investigate whether roasting affects the postprandial glucose area under the curve (AUC).
Inclusion criteria: inclusion criteria:

 Body mass index (BMI) of 18.0-30.0 kg/m2 and with no known diseases

Exclusion criteria: :

 systemic infections,

 psychiatric or metabolic disorders,

 known food allergies or intolerances related to the products used in the study (e.g. dairy or gluten),

 ongoing or former drug abuse,

 high intake of alcohol (defined as a weekly intake of >7 units for women and > 14 units for men),

 pregnancy or ongoing planning of pregnancy,

 vegetarianism or veganism,

 participation in other scientific studies during the study period, and

 blood donation during - or in the month leading up to - the study period


A Study of Skin and Systemic Biomarkers In Patients With Active Cutaneous Lupus Erythematosus And In Healthy Volunteers

Summary: The purpose of this study is to obtain skin, blood, and urine samples from patients with active cutaneous lupus lesions and from healthy participants.
Inclusion criteria: inclusion criteria:

 Have Discoid Lupus Erythematosus (DLE) or Subacute Cutaneous Lupus Erythematosus (SCLE) with or without a diagnosis of Systemic Lupus Erythematosus (SLE)

 Active DLE or active SCLE confirmed by histological analysis (for participants with DLE or SCLE without SLE)

 Confirmed diagnosis of SLE using American College of Rheumatology criteria and has current or historical positive antinuclear antibodies (ANA) or anti double-stranded deoxyribonucleic acid (anti-dsDNA) (for participants with DLE or SCLE with SLE)

 An active skin lesion that can be biopsied (for participants with lupus erythematosus)

Exclusion criteria: :

 Known or thought to have a diagnosis of drug-induced lupus

 An active skin disease that is not a manifestation of lupus erythematosus

 Has an acute cutaneous lupus erythematosus rash only

 If taking anti-malarial therapy has not been on a stable dose for at least 8 weeks before Day 1

 Participants treated with greater than 10mg/day of prednisone therapy or equivalent in the last 4 weeks prior to Day 1

 Positive serology for human immunodeficiency virus antibody, hepatitis B virus, or hepatitis C virus

['Skin biopsy', 'Blood collection', 'Urine collection']

Skin biopsy
Blood collection
Urine collection

['Healthy', 'Lupus Erythematosus, Cutaneous', 'Lupus Erythematosus, Systemic', 'Lupus Erythematosus, Discoid']

Healthy
Lupus Erythematosus
Cutaneous
Lupus Erythematosus
Systemic
Lupus Erythematosus
Discoid


Lupus Immunosuppressive/Immunomodulatory Therapy or Stem Cell Transplant (LIST)

Summary: Systemic lupus erythematosus, also known as lupus or SLE, is a chronic, multisystem, autoimmune disease in which the body's internal system of defense attacks its own normal tissues. This abnormal autoimmune response can result in damage to many parts of the body, especially the skin, joints, lungs, heart, brain, intestines, and kidneys. Both genetic and environmental risk factors are involved in the development of lupus, but these are poorly understood.~SLE has an overall 10-year survival between 80 and 90%. However, we estimate that severe lupus not responding to the usual available treatments has a 50% mortality rate in 10 years. Kidney problems occur in 30% to 50% of lupus patients and may progress to kidney failure. Kidney disease due to lupus occurs more frequently in African-Americans and Hispanics. Lupus can affect many parts of the body and cause damage, but the severe form can result in death from kidney disease; cardiovascular disease, specifically atherosclerosis; central nervous system disease; and infections.~Currently, no single standard therapy for treatment of severe SLE exists. Usually physicians prescribe an aggressive regimen of one or a combination of immunosuppressive/immunomodulatory treatments. This approach to therapy for all forms of severe SLE derives largely from studies of lupus nephritis. Current treatment, although effective in many people, are not effective in all patients and are associated with drug-induced morbidity. The design of the control arm for this study reflects the current status of treatment of SLE in the academic setting. Investigators may choose from a list of commonly used and currently available immunosuppressive/immunomodulatory treatments to optimize the treatment of their patients, based on their past treatment history and response to those treatments. Study treatments may consist of corticosteroids, cyclophosphamide (CTX), azathioprine, methotrexate, cyclosporine, mycophenolate mofetil (MMF), plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and leflunomide. Treatment may be changed as frequently and as necessary within the first year of the study to control the manifestations of SLE in each patient. New therapies that become available during the course of this trial may be added to the list of approved medications for this study.~In response to the absence of a uniformly effective treatment for severe lupus, autologous hematopoietic stem cell transplantation (HSCT) has been proposed as a potential therapy. Hematopoietic stem cells are immature blood cells that can develop into all of the different blood and immune cells the body uses. Researchers believe that resetting the immune system may stop or slow down the progression of the disease. The main purpose of this study is to compare two ways of treating SLE: 1) high-dose immunosuppressive therapy (HDIT) followed by HSCT and 2) currently available immunosuppressive/immunomodulatory therapies.
Inclusion criteria: inclusion criteria:

 Male or female subjects between the ages of 18 and 60 years, inclusive

 Meet at least 4 of 11 American College of Rheumatology (ACR) Revised Classification Criteria for SLE

 Have at least one of the following conditions defining severe steroid refractory disease:

 a) Lupus nephritis - Subjects must have severe disease, defined as meeting criteria for BILAG renal category A, and be corticosteroid dependent while receiving at least 6 months of pulse CTX at doses of 500 to 1000 mg/m2 every 4 weeks or MMF at of 2 g/day or greater. If nephritis is to constitute the sole eligibility, a renal biopsy performed within 11 months of the date of screening must show ISN/RPS 2003 classification of lupus nephritis Class III or IV disease. A renal biopsy must demonstrate the potential of a reversible (non-fibrotic) component. b) Visceral organ involvement other than nephritis - Subjects must be without mesenteric vasculitis. The subject must be BILAG cardiovascular/respiratory category A, vasculitis category A, or neurologic category A, and be corticosteroid dependent while receiving at least 3 months of oral (2 to 3 mg/kg/day or greater) or IV CTX (500 mg/m2 or greater every 4 weeks). c) Cytopenias that are immune-mediated - Subjects must be BILAG hematologic category A and be corticosteroid dependent while receiving at least one of the following: azathioprine at 2 mg/kg/day or greater for at least 3 months, MMF at 2 g/day or greater for more than 3 months, CTX at 500 mg/m2 or greater intravenously every 4 weeks or 2 mg/kg/day orally for at least 3 months, cyclosporine at 3 mg/kg/day or greater for at least 3 months, or have had a splenectomy. d) Mucocutaneous disease - Subjects must meet BILAG mucocutaneous category A and be corticosteroid dependent while receiving at least 1 of the following: azathioprine at 2 mg/kg/day or greater for at least 3 months; methotrexate at 15 mg/week or greater for at least 3 months; CTX at 500 mg/m2 or greater intravenously every 4 weeks or 2 mg/kg/day or greater orally for at least 3 months, cyclosporine at 3 mg/kg/day or greater for at least 3 months, or MMF at doses 2 g/day or greater for at least 3 months. e) Arthritis/myositis - Subjects must meet BILAG musculoskeletal category A and be corticosteroid dependent while receiving at least one of the following: azathioprine at 2 mg/kg/day or greater for at least 3 months, methotrexate at 15 mg/week or greater for at least 3 months, CTX at 500 mg/m2 or greater intravenously every 4 weeks or 2 mg/kg/day or greater orally for at least 3 months, MMF at 2 g/day or greater for at least 3 months, or cyclosporine at 3 mg/kg/day or greater for at least 3 months.

 Have the ability and willingness to provide written informed consent. In case of lupus cerebritis, a person designated by the subject may give consent.

 Must be ANA positive

Exclusion criteria: :

 HIV positive status

 Any active systemic infection

 Hepatitis B surface antigen positive

 Hepatitis C PCR positive

 Use of immunosuppressive agents for other indications other than SLE

 Any comorbid illness that in the opinion of the investigator would jeopardize the ability of the subject to tolerate therapy

 For lupus nephritis: renal biopsy, performed within 11 months of the screening date, showing Class I, II, or V disease or Class III or IV disease in conjunction with total sclerosis of 50% or more of the glomeruli

 Ongoing cancer. Patients with localized basal cell or squamous skin cancer are not excluded.

 Pregnancy, unwillingness to use acceptable means of birth control, or unwilling to accept or comprehend irreversible sterility as a side effect of therapy

 Psychiatric illness or mental deficiency not due to active lupus cerebritis making compliance with treatment or informed consent impossible

 Hemoglobin adjusted diffusion capacity test (DLCO) less than 30% at screening

 Resting left ventricular ejection fraction (LVEF) 40% or less as evaluated by echocardiogram

 History of an allergic reaction or hypersensitivity to Escherichia coli recombinant proteins, CTX, or any part of the investigative or control therapy

 SGOT/SGPT greater than 2 x the upper limit of normal, unless due to active lupus

 ANC 1000 or greater if not due to active SLE

 Subdural hematoma or any active intracranial bleeding documented within 30 days of the screening visit

 Failure to be approved for participation in this study by the SCSLE Protocol Eligibility Review Committee

 Positive tuberculin skin test

 Presence of mesenteric vasculitis

['Leukapheresis', 'Non-myeloablative high dose immunosuppressive therapy conditioning (HDIT)', 'Autologous CD34+HPC transplantation (HSCT)', 'Plasmapheresis', 'Rabbit anti-thymocyte globulin', 'Methylprednisolone', 'Growth colony stimulating factor (G-CSF)', 'Corticosteroids', 'Mycophenolate mofetil', 'Azathioprine', 'Intravenous immunoglobulin', 'Methotrexate', 'Rituximab', 'Leflunomide']


Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism

Summary: The purpose of this study is to investigate if selenium supplementation to the standard treatment with anti-thyroid drugs in patients with Graves' hyperthyroidism, will lead to a fewer people with anti-thyroid treatment failure and faster remission, in terms of better quality of life during the first year of treatment and more patients staying in remission.
Inclusion criteria: inclusion criteria:

 Age 18 years or older.

 Active Graves' hyperthyroidism (suppressed TSH (< 0.1) and positive TRAb) measured within the last two months prior to the inclusion date.

 Written informed consent

Exclusion criteria: :

 Major co-morbidity, making the participants unlikely to continuously receive trial intervention in the intervention period.

 Previous treatment with radioactive iodine.

 Current ATD treatment having been received for more than two months.

 Treatment with immunomodulatory drugs, such as cyclosporine A, methotrexate, cyclophosphamide.

 Allergy towards the components in the selenium and placebo pills.

 Pregnant or breast-feeding women.

 Intake of selenium supplementation above 70 µg per day (70 µg corresponds to the amount in a multivitamin tablet).

 Unable to read and understand Danish.

 Lack of informed consent


Immuno-modulation in Amyotrophic Lateral Sclerosis- a Phase II Study of Safety and Activity of Low Dose Interleukin-2

Summary: The primary objective is to evaluate in ALS patients the regulatory T cell early response to two low-doses of IL-2 at 1 and 2 MIU per day after one course of 5 consecutive days comparatively to placebo.
Inclusion criteria: inclusion criteria:

 The patient has been correctly informed

 The patient must have given his/her informed and signed consent.

 The patient must be insured or beneficiary of a health insurance plan.

 The patient is at least 18 years old and less than 75 years old

 Probable, or laboratory-supported probable or definite ALS as defined by El Escorial Revised ALS diagnostic criteria (according to Airlie House Conference 1988)

 Stable on riluzole treatment for more than 3 months with liver function test results < 2ULN

 Disease duration ≤ 5 years

 Vital capacity ≥ 70% of normal

 Ability to swallow without the requirement for nasogastric or PEG feeding

 Agreement for patient to use an adequate method of contraception throughout the study and for 2 weeks after post study visit

 The patient is available and willing to participate in seven study visits occurring at the CHU within the next six months

Exclusion criteria: :

 The patient is participating in another interventional study

 Within the past three months, the patient has participated in another interventional

 The patient is in an exclusion period determined by a previous study

 The patient is under judicial protection

 The patient is an adult under guardianship

 The patient refuses to sign the consent

 It is impossible to correctly inform the patient

 Other life threatening disease

 Presence of contra-indicated concomitant treatments or with potential neuroprotective benefit (see section 11.2 of the protocol)

 Presence of tracheostomy or non-invasive ventilation

 Use of Percutaneous endoscopic gastrostomy (PEG) or nasogastric tube

 Presence of clinical infection (treated or untreated)

 Positive serology for CMV, EBV (confirmed by viral load), or HIV

 Vaccination within 8 weeks prior to first experimental dosing

 Other disease precluding functional assessments

 Cancer within the past 5 years (except stable non-metastatic basal cell skin carcinoma or in situ carcinoma of the cervix)

 Severe cardiac or pulmonary disease

 Documented auto-immune disorders except asymptomatic Hashimoto thyroiditis

 Women of child bearing age without contraception or pregnant or breast feeding

 Any clinically significant laboratory abnormality (excepting cholesterol, triglyceride and glucose)

['Placebo', '1.0 MIU IL-2 per day', '2.0 MIU IL-2 per day']

Placebo
1.0 MIU IL-2 per day
2.0 MIU IL-2 per day


Effect of Remifentanil on the Recovery Profile After Prolonged Head and Neck Surgery

Summary: Opioid tolerance in the perioperative period is inevitable especially with ultra-short acting agents such as remifentanil. Existing evidence had shown that opioid induced hyperalgesia due to neuroplastic changes in the central as well as peripheral nervous system leads to sensitization of pro-nociceptive pathways. However there has been a controversy of occurrence of such tolerance following the use of remifentanil and the quality of recovery as compared to conventional opioids. The investigators evaluated the occurrence of opioid tolerance and other significant adverse effects with remifentanil in subjects undergoing head and neck surgeries. The investigators studied ASA physical status I and II adult subjects undergoing elective head and neck procedures, under general anesthesia with minimum expected duration of 2 hours. The remifentanil infusion was used in one group and intermittent boluses of morphine or fentanyl administered in another group. They were evaluated for immediate post-operative pain by using numerical rating scale (NRS), the opioid consumption, post-operative nausea, vomiting, other significant adverse effects of remifentanil and the time to discharge from PACU.
Inclusion criteria: inclusion criteria:

 Patients with ASA I to II, scheduled for elective head and neck surgery with minimum expected duration of 2 hours, requiring general anesthesia

Exclusion criteria: :

 previous history of either drug or alcohol abuse those who have been using opioids for long term mental disorder with difficult to understand pain scoring system ASA physical status of III and above surgical procedure warranting elective postoperative ventilation

['Remifentanil', 'choice of intra-operative opioids were left to the discretion of anesthesiologist']


Efficacy of Artesunate-amodiaquine (AS-AQ) in Children With Malaria and Severe Acute Malnutrition, Madaoua, Niger 2010

Summary: The purpose of the study is to determine whether the artesunate-amodiaquine combination is effective in treating uncomplicated Plasmodium falciparum malaria in children with severe acute malnutrition.~Infection with Plasmodium falciparum malaria remains a significant cause of morbidity and mortality in malnourished children. Malnutrition is known to have a modulating effect on the incidence of malaria infections, its severity and effectiveness of treatments. However, little data exists on antimalarial drug efficacy in malnourished children. Artesunate-amodiaquine combination is the first line treatment used in Médecins Sans Frontières programmes in Niger. The assumption of current efficacy of artesunate-amodiaquine is based on non malnourished children. The aim of this study is to measure the clinical and parasitological efficacy in severely malnourished children.~The study is consistent with the standard WHO protocol for monitoring antimalarial drug efficacy (WHO: Methods for surveillance of antimalarial drug efficacy. Geneva; 2009), except for one inclusion criterion. Severe acute malnutrition is an inclusion criteria, instead of being an exclusion criteria. The study will encompass a pharmacokinetic part that will provide important information on the absorption of the drug.
Inclusion criteria: inclusion criteria:

 Age between 6 and 59 months

 Weight ≥5kg

 P. falciparum monoinfection confirmed on a thick blood film

 Parasitic density between 1,000 and 200,000 asexual forms/uL of blood

 Measured axillary temperature ≥37.5°C or history of fever during the previous 24 hours

 Severe malnutrition (defined as a weight/height ratio less than -3 z-scores)

 High probability of compliance with follow-up visits (home is within two hours of walk from the outpatient department, no near-term travel plans, etc..)

 Consent of a parent or guardian who is at least 18 years of age.

Exclusion criteria: :

 Signs of a critical illness as defined by the WHO (WHO (2000) Severe falciparum malaria; Clinical features of severe falciparum malaria in children. Royal Society of Tropical Medicine and Hygiene, 94 (supplement 1), 5-11).

 Signs of severe or complicated malaria as defined by the WHO (WHO (2000) Severe falciparum malaria; Clinical features of severe falciparum malaria in children. Royal Society of Tropical Medicine and Hygiene, 94 (supplement 1), 5-11).

 Severe anaemia (haemoglobin <5 g/dL)

 Known history of hypersensitivity to any of the study medications,

 Symmetric oedema in the feet,

 Concomitant febrile illness not originating from malaria, which could alter the outcome of the study (measles, acute lower respiratory tract infection, otitis media, tonsillitis, abscesses, severe diarrhea with dehydration, etc.),

 History of a full treatment course with the study drug in the past 28 days.

['Malaria, Falciparum', 'Malnutrition', 'Child']


Advanced Oesophageal Cancer Study to Compare Quality of Life and Palliation of Dysphagia.

Summary: To compare the treatment of gullet cancer with radiotherapy alone and assess the advantage and toxicity of adding chemotherapy. The hypothesis to be tested is as follows: That the addition of chemotherapy to a short course of radiation treatment improves the proportion of patients who achieve relief of dysphagia and improves quality of life compared to radiation alone in patients with advanced oesophageal cancer.
Inclusion criteria: inclusion criteria:

 Biopsy proven Carcinoma of the oesophagus.

 Not a candidate for radical/curative treatment due to the advanced nature of the disease, presence of metastases, or intercurrent illness. (It should be noted that, patients with mediastinal nodes and no more distant disease maybe suitable for radical treatment).

 Symptomatic patients with dysphagia scores of ≥ 1 i.e. able to eat only some solids (see Mellow Scale appendix 1)

 Performance status ECOG ≤ 2

 Patients must begin treatment within 2 weeks of randomization.

 Patient is at least 18 years old.

 Adequate haematological function to undergo chemotherapy. Peripheral blood - Neutrophils > 1.5 x 10^9/L - Platelets > 100 x 10^9/L

 Adequate renal function, Creatinine - Calculated clearance ≥ 50 ml/min

 Patients capable of childbearing are using adequate contraception.

 Written informed consent of patient.

Exclusion criteria: :

 Previous mega-voltage external beam Radiotherapy or brachy-therapy delivered to the region of the chest.

 Synchronous active malignancies.

 Pregnant or lactating patients.

 Patients unfit for any treatment component.

 Tracheo-oesophageal fistula.

 Stents in situ.

 Previous chemotherapy for Oesophageal Cancer

 CT scan of thorax and abdomen more than 8 weeks prior to randomization

 Full Blood Count, Biochemistry (including creatinine) and creatinine clearance more than 2 weeks prior to randomization


Far Infrared Radiation Treatment for Bipolar Condition

Summary: A preliminary study to determine the possibility of using far infrared radiation for the treatment of the Bipolar Condition
Inclusion criteria: inclusion criteria:

 Persons with Bipolar Condition, Depression, Anxiety, Stress and Insomnia

Exclusion criteria: :

 Persons with severe mental illness that are confined to mental hospitals etc. as defined by the USA Diagnostic and Statistical Manual of Mental Disorders (DSM) are excluded from this clinical trial.


A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma

Summary: The primary objective of this study is to determine the response rate, duration of response,progression-free survival and overall survival of subjects with advanced melanoma treated with TH-302.
Inclusion criteria: inclusion criteria:

 At least 18 years of age

 Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's Regional Ethics Board/Independent Ethics Committee (REB/IEC)

 Histologically documented cutaneous or mucosal malignant melanoma, which is recurrent or metastatic and is not curable by surgical or other means.

 Adequate tumour tissue (greater than 0.5cm3 preferred, 3 X core biopsy acceptable) available and agreement from subjects that this tissue from their primary and/or metastatic tumour be made available for assessment of potential biomarkers.

 Ability and availability to complete all prescribed biomarker studies (Screening and after Cycle 2).

 Recovered to Grade 1 from reversible toxicities of prior therapy

 Presence of clinically and/or radiologically documented disease. At least one site of disease (which will not be removed during the course of the study) must be uni-dimensionally measurable as per RECIST 1.1 or clinically quantifiable (such as in the case of skin disease)

 ECOG performance status of 0 - 1.

 Prior treatment with any number of immunotherapies (e.g., IL2, ipilimumab), targeted therapies (e.g., vemurafenib) are permitted but no more than one 1 prior chemotherapy

 Acceptable liver function

 Acceptable renal function

 Acceptable hematologic status (without growth factor support for neutropenia or transfusion dependency):

 Normal 12-lead ECG (clinically insignificant abnormalities permitted)

 Female subjects of childbearing age must have a negative urine HCG test unless prior hysterectomy or menopause (defined as age above 55 and twelve months without menstrual activity). Female subjects should not become pregnant or breast-feed while on this study. Sexually active male and female subjects should use effective birth control.

Exclusion criteria: :

 Anticancer treatment with radiation therapy, targeted therapies, chemotherapy, immunotherapy, hormones or other antitumour therapies within 28 days prior to first dose of TH-302.

 Subjects who have received any other investigational drug or agent within 28 days of first dose of TH-302

 Current use of drugs with known cardiotoxicity

 Significant cardiac dysfunction:

 Seizure disorders requiring anticonvulsant therapy

 Progressing brain metastases (unless previously treated and stable disease for a period of greater than or equal to 3 months on repeat MRI following definitive treatment).

 History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for greater than 2 years

 Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation less than 90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause hypoxia of normal tissue.

 Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, without complete recovery

 Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

 Prior therapy with an hypoxic cytotoxin

 Known infection with HIV or active infection with hepatitis B or hepatitis C

 History of allergic reaction to a structural compound or biological agent similar to TH-302

 Pregnancy or breast-feeding

 Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

 Unwillingness or inability to comply with the study protocol for any reason.


A Clinical Trial to Prevent the Complications of Insulin Resistance (Including Type-2 Diabetes)

Summary: The goal of this study is to aggressively treat insulin resistance and its clinical manifestations when they first appear in childhood, and to prevent the subsequent progression towards impaired glucose tolerance and type-2 diabetes. In the process of this clinical trial, we will learn more about the early manifestations of insulin resistance, its treatment, and its relationship to obesity and type-2 diabetes through parallel in-vivo and in-vitro studies.
Inclusion criteria: inclusion criteria:

 Obese patients (wt > 95th percentile for age, for adults increased BMI > 27) greater than 5 years of age

 And/or presence of complications of insulin resistance such as acanthosis nigricans, dyslipidemia, elevated blood pressure, hyperandrogenism

 Siblings and parents of patients with insulin resistance. Siblings and parents will be included only in the case of documented insulin resistance in the index subject. Insulin resistance will be documented by OGTT and/or IVGTT.

 Family history of type II diabetes.

Exclusion criteria: :

 Critically ill patients, patients will congestive heart failure, renal or liver insufficiency

 Inability to give consent.

 History of poor compliance with physician's recommendations

['Metformin', 'skin biopsy', 'diet and exercise', 'pioglitazone', 'rosiglitazone']

Metformin
skin biopsy
diet and exercise
pioglitazone
rosiglitazone

['Insulin Resistance', 'Diabetes Mellitus']


Pancreatic Insufficiency Secondary to Tobacco Exposure

Summary: Pancreatic insufficiency is a condition in which there is a decrease in the production and release of enzymes made in the pancreas, which causes nutrient malabsorption. There are many chronic diseases that can lead to pancreatic insufficiency. In the early stages of this disease, a patient may not experience any symptoms, and the prevalence of pancreatic insufficiency may be underestimated. Smoking has long been recognized as a cause of disease in many organs in the body. Cigarette smoke causes inflammation and damages tissue, including the pancreas. Studies have shown that smoking is an independent risk factor for pancreatic cancer and chronic pancreatitis. It has also been shown that the more a person smokes, the worse his disease will be. Additionally, there are studies that show that smokers have nutritional deficiencies. There are observational and retrospective studies that suggest that pancreatic insufficiency may also be caused by smoking. However, this has not been established, and the relationship has not been examined in a controlled manner. This study examines the relationship between smoking and pancreatic insufficiency in patients who do not have other pancreatic diseases.
Inclusion criteria: inclusion criteria:

 Male or female at least 30 years of age

 Able to read, understand, and sign informed consent

 Patients with a negligible smoking history (defined as no smoking for the past 7 years, and a total smoking history ≤ 5 pack-years) OR patients with AT LEAST a 20 pack-year smoking history

Exclusion criteria: :

 Patients with a prior diagnosis of pancreatic insufficiency

 Patients who have a current or remote history of acute or chronic pancreatitis or any other primary pancreatic disease or malignancy

 Patients who have had pancreatic surgery

 Patients with a diagnosis of small bowel malabsorption or Celiac disease

 Patients with any other significant systemic disease that is deemed by the investigator as possibly interfering with the conduct or interpretation of the study


Study of Neurological Complication After Radiotherapy for High Grade Glioblastoma

Summary: The survival time and the number of long time survivors after radiotherapy in brain cancer patients have increased for the last decades. Therefore the topic of late-delayed neurotoxic effects of this therapy gains more and more importance. Among these side effects, the main and most frequent one is the leukoencephalopathy, a diffused and progressive damage of the white matter characterized by myelin loss, loss of axons and vascular lesions. The incidence rate assessment, as well as the occurrence time, is based on retrospective studies with low numbers of patients, but seems to reach 30 to 50 % of the patients according to the follow-up. The risk seems to be increased during the first two years after the radiotherapy, but persists for decades.~To gain further insight in the radiation-induced leukoencephalopathy, the objective of this project is to study the onset and evolution of leukoencephalopathy in a 3-year prospective cohort of patients having undergone cerebral radiotherapy for glioma (stage 3-4), using specific cognitive tests, Magnetic Resonance Imagery (MRI) scans of the brain and predictive bio-markers of cognitive impairments.
Inclusion criteria: inclusion criteria:

 - diagnosis of glioma (stage 3 to 4)

 both genders

 age > 18 years

 treatment by radiotherapy and chemotherapy

 clinical monitoring post radiotherapy in Neurology Department, Pitié-Salpêtrière University Hospital and in the radiotherapy department of the Paul Strauss Institute.

Exclusion criteria: :

 - other neurological tumors and brain metastases

 psychiatric severe illness, including severe depression


RCT of the 4mm vs. the 8mm Collimator for GKR of Brain Micrometastases

Summary: Gamma Knife Radiosurgery (GKR) is a well-established treatment modality for brain metastasis (Chiou 2013; Salvetti, Nagaraja et al. 2013). Large multicentre series have been published on patients with single and multiple cerebral metastases, treated with GKR over a period of 30 years (Karlsson, Hanssens et al. 2009). Multiple institutions have reported a consistently high local tumour control rate of 80%-90% following GKR (Chang, Lee et al. 2000; Da Silva, Nagayama et al. 2009; Salvetti, Nagaraja et al. 2013).~There is controversy over the use of GKR and/or Whole Brain Radiotherapy (WBRT) in patients with multiple metastases. WBRT provides a lower rate of distant recurrences, whereas GKR achieves good local control of treated lesions without the deleterious side effects of radiotherapy (Lippitz, Lindquist et al. 2014). This discussion is mainly focused on the risk of distant recurrences, which is lower if WBRT is given. There is evidence showing that Radiosurgery (RS) based on high contrast/resolution stereotactic MRI decreases the incidence and lengthens the time to distant recurrences (Hanssens, Karlsson et al. 2011). As a result, the current tendency is to treat all the lesions visible in high contrast/resolution images the day of Gamma Knife; which is followed by regular MRI follow ups and subsequent GKR for distant recurrences in order to avoid/delay WBRT.~It has been estimated that more than a half of distant recurrences will grow from tumour cells that were already in the brain (as micrometastases) when radiosurgery is delivered, but not much has been studied on the optimal prescription and radiation delivery method for these lesions. There is controversy over which collimator should be used when treating micro-metastases (BmM). These lesions can either be treated with the 4mm collimator at an isodose between the 40% and 90%, or the 8mm collimator at an isodose above 90%. The 8 mm collimator is thought to offer better Local Control Rate (LCR) with the advantage of faster delivered treatments, while the 4 mm collimator is considered to be safer, given its steep dose fall-off. It is the aim of this study to find out which of the 4 mm or 8 mm collimators can achieve the higher LCR with less complications. A large number of lesions will be randomised to either the 4 or the 8 mm collimator and the patients followed up to evaluate clinical efficacy.
Inclusion criteria: inclusion criteria:

 Adult patients with brain metastasis from any primary tumour receiving GKR.

 All intracranial micro-metastases including lesions located in the cerebral hemispheres, thalamus, basal ganglia and cerebellum and excluding lesions located in the brain stem below the level of the superior colliculi.

 Target volume < 0.14 cc3 and maximum diameter < 7 mm.

 The subject consents to participate in the study.

Exclusion criteria: :

 Inability to consent

 Younger than 18 years of age.

 Lesions in the brainstem (below the level of the superior colliculi) are better treated with the 4 mm collimator and they will be excluded from the study.

 Patients with more than 25 brain lesions suitable for randomisation will be excluded from the study.

 Co-morbidity or previous treatment such as surgery, chemotherapy or WBRT is not to be considered as

['GKR with a single shot of the 8 mm collimator', 'GKR with a single shot of the 4 mm collimator']


Prevention of Gastric Ulcer Bleeding by Using Computer-alert in General Practice

Summary: The purpose of this study is to investigate if a computerised decision-support tool used in general practice, can reduce the frequency of peptic ulcer bleeding related to the use of NSAIDs (Non-Steroidal-antiinflammatory-drug) and ASA( Acetylsalicylic acid) .~On the basis of The Danish general medical database it is possible to develope a computerised decision-support tool, which enables the general practitioner (GP) in a pop-up window to get information on each patients risk-factors, when prescribing NSAID and aspirin to a patient at risk. This will give the general practitioner the oppurtunity to choose a different type of preparation or prescribe ulcer-preventive medicine at the same time.~The decision-support tool will be tested in a randomized trial among general practitioners. The aim is to reduce the occurence of peptic ulcer bleeding. The expected outcome is a reduction in half of the total numbers of peptic ulcers.
Inclusion criteria: inclusion criteria:

 General practitioners in the Region of Southern Denmark which are linked to Danish General Medical Database for minimum 6 months

Exclusion criteria: :

 -

['Computer-alert', 'A computer alerts which pops up when the GP presribes NSAID/ASA to a patient with risk-factors', 'Computer-alert']


A Behavioral Therapy for Insomnia Co-existing With COPD

Summary: Difficulty falling asleep, staying asleep or poor quality sleep (insomnia) is common in people with chronic obstructive pulmonary disease. Insomnia is related to greater mortality, with four times the risk of mortality for sleep times < 300 minutes. Insomnia is also related to greater morbidity, with 75% greater health care costs than people without insomnia. However, insomnia medications are used with caution in COPD due to potential adverse effects. Common features of COPD such as dyspnea, chronic inflammation, anxiety and depression also affect insomnia and can interfere with therapy outcomes. While cognitive behavioral therapy for insomnia (CBT-I), a therapy that provides guidance on changing unhelpful sleep-related beliefs and behavior, is effective for people with primary insomnia and people with other chronic illnesses, the efficacy and mechanisms of action of such a therapy are yet unclear in people with both insomnia and COPD. The objective in this application is to rigorously test efficacy of two components of insomnia therapy - CBT-I and COPD education (COPD-ED) - in people with coexisting insomnia and COPD, and to identify mechanisms responsible for therapy outcomes. The central hypothesis is that both CBT-I and COPD-ED will have positive, lasting effects on objectively and subjectively measured insomnia and fatigue. The rationale for the proposed study is that once the efficacy and mechanisms of CBT-I and COPD-ED are known, new and innovative approaches for insomnia coexisting with COPD can be developed, thereby leading to longer, higher quality and more productive lives for people with COPD, and reduced societal cost due to the effects of insomnia. The investigators plan to test our central hypothesis by completing a randomized controlled comparison of CBT-I, COPD-ED and non-COPD, non-sleep health education attention control (AC) using a highly efficient 4-group design. Arm 1 comprises 6 weekly sessions of CBT-I+AC; Arm 2=6 sessions of COPD-ED+AC; Arm 3=CBT-I+COPD-ED; and Arm 4=AC. This design will allow completion of the following Specific Aims: 1. Determine the efficacy of individual treatment components, CBT-I and COPD-ED, on insomnia and fatigue. 2. Define mechanistic contributors to the outcomes after CBT-I and COPD-ED. The research proposed in this application is innovative because it represents a new and substantive departure from the usual insomnia therapy, namely by testing traditional CBT-I with education to enhance outcomes.
Inclusion criteria: inclusion criteria:

 mild to very severe COPD.

 age ≥ 45 years of age with no other major healthproblems.

 clinically stable at the time of enrollment into the study.

 insomnia.

Exclusion criteria: :

 evidence of restrictive lung disease or asthma.

 pulse oximetry reading of < 90% at rest or < 85% at night for > 5 min.

 evidence of a major sleep disorder other than insomnia.

 hypnotic use.

 acute respiratory infection within the previous 2 months.

 presence of a potentially debilitating disease such as cancer, congestive heart failure, kidney disease, liver failure or cirrhosis; evidence of alcohol or drug abuse, musculoskeletal or degenerative nerve disease.

 a self-reported current diagnosis of major depression or psychiatric disease or a Hospital Anxiety and Depression Scale (HADS) depression score of > 11.

 currently participating in pulmonary rehabilitation.

['Cognitive Behavioral Therapy for Insomnia', 'COPD Education', 'Attention Control']

['Insomnia', 'COPD', 'Chronic Obstructive Pulmonary Disease', 'Fatigue']

Insomnia
COPD
Chronic Obstructive Pulmonary Disease
Fatigue


Open Label Ganciclovir Therapy for Sight- or Life-Threatening Cytomegalovirus Disease in the Immunocompromised Patient

Summary: To make intravenous (IV) ganciclovir available to immunocompromised patients with life-threatening or sight-threatening Cytomegalovirus (CMV) infection, where the symptoms of the disease are too severe to allow admission to a controlled clinical study of ganciclovir therapy. To determine the safety and tolerance of 2 - 3 weeks induction course of ganciclovir IV followed by a maintenance course of ganciclovir IV for an indefinite duration. To tabulate the patient's clinical response.
Inclusion criteria:
Exclusion criteria:

 Co-existing Condition:

 Patients with the following are excluded:

 Cytomegalovirus (CMV) disease who meet the criteria for a treatment IND protocol, or other clinical studies, including controlled clinical studies of anticytomegalovirus therapy in peripheral CMV retinitis in patients with AIDS.

 Mild to moderate CMV infections who fail to meet the severity criteria. CMV syndrome (i.e., cytopenia, increased liver enzymes, fever, viremia, viruria) is not considered immediately life-threatening.

 Transplant patients in whom trial reduction of immunosuppressive drug treatment is feasible.

 Children with congenital or neonatal CMV where there is not a documented primary or acquired immunodeficiency.

 Hypersensitivity to acyclovir or ganciclovir.

 Receiving antimetabolite treatment that cannot be discontinued.

 Concurrent Medication:

 Excluded:

 Antimetabolites.

 Alkylating agents.

 Nucleoside analogs (topical ophthalmics are permitted).

 Interferon.

 Foscarnet.

 Cytokines.

 Patients with the following are excluded:

 Cytomegalovirus (CMV) infection who meet the criteria for a treatment IND protocol, or other clinical studies, including controlled clinical studies of anticytomegalovirus therapy in peripheral CMV retinitis in patients with AIDS.

 Mild to moderate CMV infections who fail to meet the severity criteria. CMV syndrome (i.e., cytopenia, increased liver enzymes, fever, viremia, viruria) is not considered immediately life-threatening.

 Transplant patients in whom trial reduction of immunosuppressive drug treatment is feasible.

 Children with congenital or neonatal CMV where there is not a documented primary or acquired immunodeficiency.

 Hypersensitivity to acyclovir or ganciclovir.

 Receiving antimetabolite treatment that cannot be discontinued.

 Patients must qualify as follows:

 Previously enrolled in compassionate use study (ICM 1257/1257A) or have terminated from another Syntex ganciclovir study.

 Diagnosis of AIDS and life-threatening Cytomegalovirus (CMV) infection.

 Diagnosis of other immunodeficiencies other than AIDS, with life-threatening or sight-threatening CMV disease.

['Cytomegalovirus Infections', 'Cytomegalovirus Retinitis', 'HIV Infections']

Cytomegalovirus Infections
Cytomegalovirus Retinitis
HIV Infections


Chikungunya Virus Vaccine Trial in Healthy Adults

Summary: Background:~- Chikungunya virus (CHIKV) is transmitted by mosquitoes. It can cause fever, headache, muscle pain, fatigue, and joint pain. The disease usually does not cause death. But the joint pain, which may be directly related to the infecting virus, may be severe and last for several months. CHIKV outbreaks are most common in Africa, India, and Asia. A new experimental vaccine for CHIKV has been developed, and researchers are testing it in healthy adults. Participants cannot develop CHIKV from this vaccine.~Objectives:~- To test the safety and effectiveness of a Chikungunya virus vaccine.~Eligibility:~- Healthy individuals between 18 and 50 years of age.~Design:~This study, including vaccine doses and followup tests, will last about 44 weeks. Participants will have three vaccination visits, six followup clinic visits, and three telephone contacts during this study. Vaccination visits will take about 4 hours. Most other clinic visits will usually take 2 hours. The telephone contacts will take about 15 minutes.~Participants will be screened with a physical exam and medical history. Blood samples will also be collected.~Participants will be assigned to one of three dose groups. Information about doses will be provided before the start of the vaccinations.~Vaccine injections will be given at the start of the study, at 4 weeks, and at 20 weeks. Participants will be asked to keep an eye on the injection site for 7 days and to notify researchers if there are any side effects.~Participants will be monitored throughout the study with blood samples and clinic visits.
Inclusion criteria: inclusion criteria:

 A participant must meet all of the following criteria:

 18 to 50 years old

 Available for clinical follow-up through Week 44

 Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process

 Complete an Assessment of Understanding prior to enrollment and verbalize understanding of all questions answered incorrectly

 Able and willing to complete the informed consent process

 Willing to donate blood for sample storage to be used for future research

 In good general health, with a BMI less than or equal to 40, without clinically significant medical history, and has satisfactorily completed screening

 Physical examination and laboratory results without clinically significant findings within the 56 days prior to enrollment

 Laboratory Criteria within 56 days prior to enrollment:

 Hemoglobin greater than or equal to11.5 g/dL for women; greater than or equal to13.5 g/dL for men

 WBC: 3,000-12,000 cells/mm(3).

 Differential either within institutional normal range or accompanied by physician approval

 Total lymphocyte count: greater than or equal to 800 cells/mm(3)

 Platelets = 125,000-500,000/mm(3)

 Alanine aminotransferase (ALT) less than or equal to 1.25 times upper limit of normal range

 Serum creatinine less than or equal to1x upper limit of normal (less than or equal to1.3 mg/dL for females; less than or equal to1.4 mg/dL for males).

 Negative FDA-approved HIV blood test

 Female-Specific Criteria

 Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential

 A woman of childbearing potential must agree to use an effective means of birth control from at least 21 days prior to enrollment through 12 weeks after last study vaccination

Exclusion criteria: :

 A participant will be excluded if one or more of the following conditions apply:

 Female-Specific Criteria

 Woman who is breast-feeding or planning to become pregnant during the time projected for individual study participation

 Systemic immunosuppressive medications or cytotoxic medications within 12 weeks prior to enrollment [with the exceptions that a short course of corticosteroids (less than or equal to10 days duration or a single injection) for a self-limited condition at least 2 weeks prior to enrollment will not exclude study participation]

 Blood products within 16 weeks prior to enrollment

 Immunoglobulin within 8 weeks prior to enrollment

 Prior vaccinations with an investigational CHIKV vaccine

 Investigational research agents within 4 weeks prior to enrollment

 Live attenuated vaccines within 4 weeks prior to enrollment

 Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 2 weeks prior to enrollment

 Current anti-TB prophylaxis or therapy

 Subject has a history of any of the following clinically significant conditions:

 A history of confirmed or suspected CHIKV infection

 A history of immune-mediated or clinically significant arthritis

 Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator

 Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema

 Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that is expected to require the use of oral or intravenous corticosteroids

 Diabetes mellitus (type I or II), with the exception of gestational diabetes

 Idiopathic urticaria within the past year

 Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws

 Malignancy that is active, or treated malignancy for which there is not reasonable assurance of sustained cure, or malignancy that is likely to recur during the period of the study

 Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years

 Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen

 Psychiatric condition that may preclude compliance with the protocol; past or present psychoses; disorder requiring lithium; or within five years prior to enrollment, a history of suicide plan or attempt

 Any medical condition (such as thyroid disease or hypertension that are not well controlled by medication, or viral hepatitis) that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

['Viral Vaccines', 'Chikungunya Fever', 'Chikungunya Virus Infection']

Viral Vaccines
Chikungunya Fever
Chikungunya Virus Infection


The Use of Virtual Reality for the Gait Training of Elderly Fallers

Summary: The study aims to investigate the efficacy of gait training using virtual reality to decrease the risk of falls in elderly idiopathic fallers. The investigator hypothesize that training with virtual reality would increase the ability to perform in the real world environment and decrease the risk of falls in elderly adults.
Inclusion criteria: inclusion criteria:

 between the ages of 65-85

 independent in activities of daily living

 able to walk without assistance for at least 10 minutes

 cognitively intact (Mini Mental State Exam ≥24)

 reported 2 or more falls within 6 months prior to the beginning of the study

Exclusion criteria: :

 any neurological, orthopedic or any other impairment likely to impact gait.

 severe visual impairments

 major depression as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria

['gait training', 'gait training 2', 'exercise group']

gait training
gait training 2
exercise group


Pilot Study of Cognitive Behavioral Therapy for Anxiety and Bipolar I Disorder

Summary: The specific goal of this research study is to investigate the feasibility, acceptability, and preliminary efficacy of a transdiagnostic, cognitive-behavioral therapy developed specifically to target common core processes across mood and anxiety disorders [Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP)], for the treatment of patients with bipolar I disorder (BD-I) and comorbid anxiety. The study will compare treatment-as-usual with pharmacotherapy (TAU) plus 18 one-hour sessions of treatment with the UP to TAU alone. Patients in both treatment conditions will be followed over a 12-month period and will be assessed monthly to track changes in mood, anxiety and emotion-related symptoms; functional impairment; and relapse rates. Data on the acceptability of the treatment will be gathered concurrently through monthly patient self-reported ratings of treatment satisfaction, and by tracking rates of acceptance for randomization into the study, number of completed sessions, and dropout rates. The study will examine: 1) whether combined cognitive behavioral treatment (UP) for BD-I and comorbid anxiety disorders is an acceptable and feasible approach to treatment; 2) whether treatment with the UP for BD-I and comorbid anxiety disorders as an adjunct to pharmacotherapy treatment-as-usual (TAU) leads to greater symptom reduction and reduced functional impairment than pharmacotherapy alone, 3) whether treatment for BD-I and comorbid anxiety disorders with the UP improves relapse rates over a 6-month follow-up relative to TAU; and 4) whether reduction in symptoms, relapse rates, and functional impairment are mediated by changes in emotion regulation skills. The broader aim of this study is to address the need for improved treatments for bipolar disorder.
Inclusion criteria: inclusion criteria:

 Men and women age 18-65

 DSM-IV diagnosis of bipolar I disorder and at least one of three additional anxiety disorders:

 generalized anxiety disorder, panic disorder, or social phobia.

 HAM-D-17 score <16 (i.e. depressive symptoms)

 YMRS score < 12 (i.e. no or very low manic symptoms)

 Current, stabilized (> 3 months) pharmacotherapy treatment under the care of a psychiatrist consisting of optimized, stable maintenance pharmacotherapy at maximum tolerated dosages according to Texas Implementation of Medication Algorithm.

Exclusion criteria: :

 Active suicidality (HAM-D-17 suicide item #3 score > 3) in the past 2 months. Potential participants scoring 3 or higher on the HAM-D-17 suicide item will be immediately evaluated by the PI and Sponsor and referred to a higher level of care if clinically indicated.

 DSM-IV bipolar I disorder subtype rapid cycling

 DSM-IV manic or mixed episode in the past 2 months

 DSM-IV major depressive episode in the past 2 months

 Psychotropic medication not in accordance with the revised Texas Implementation of Medication Algorithm

 Current Pregnancy

 Medical illness or non-psychiatric medical treatment that would likely interfere with study participation.

 Neurologic disorder, previous ECT, or history of head trauma (i.e. known structural brain lesion)

 Current or past history of selected DSM-IV Axis I disorders other than bipolar disorder including: organic mental disorder, substance abuse within the past 12 months and/or history of substance abuse for > 1 year; current substance dependence (including alcohol), as assessed by the Structured Clinical Interview for DSM-IV-TR, Substance Use Disorders (Section E); schizophrenia, delusional disorder, psychotic disorders not otherwise specified, obsessive compulsive disorder and posttraumatic stress disorder (due to low prevalence of

 6.5% each).

 Concurrent psychotherapy other than cognitive-behavioral therapy as provided in this study (to rule out other uncontrolled effects of concurrent psychotherapies)

 Presence of metallic implants that would interfere with safety during fMRI scanning (i.e. cardiac pacemaker, metal plates, etc.)

 Claustrophobia

['Bipolar Disorder', 'Anxiety Disorders']


Fracture of Distal Radius and Ulna Healed With Shortening of One Bone. Clinical Significance at Skeletal Maturity

Summary: The fractures of distal forearm are the most common trauma in children. Sometimes one of the bones becomes shortened as a result of fracture fragments overlap. When some amount of shortening exists, concern regarding relationship of distal radio-ulnar joint (DRUJ) arises. The common opinion is expressed in one of the textbooks and is represented by one sentence, which usually one bone shortening is well tolerated, probably does not cause a problem, and does not have clinical significance. However, pathology of ulna plus or minus variants is well described and may cause ulno-carpal abutting syndrome or radiocarpal pain. This concern may lead to more aggressive approach in treatment of a fracture, with attempts to make an equal bone length. We did not find in the literature study that investigates this problem. We postulate that obvious shortening of one bone may cause an inequality of DRUJ and can be clinically significant.
Inclusion criteria: inclusion criteria:

 Children that had had Ulna or Radius X-rays

 Signing Informed consent.

Exclusion criteria: :

 - Unwillingness to sign informed consent.


A Comparison of Two Types of Injected Nutritional Supplements in Patients With AIDS and Pneumocystis Carinii Pneumonia (PCP)

Summary: The objectives of this study are:~To establish whether there is a difference in clinical effectiveness of Liposyn II 20 percent as compared with Liposyn III 2 percent in AIDS patients with Pneumocystis carinii pneumonia (PCP). To compare the effects of the two lipid emulsions on immunologic function in AIDS patients. To compare the effect of the two lipid emulsions on HIV load in AIDS patients as measured by reverse transcriptase (RT) in culture. To determine whether a decrease in HIV infectivity is greater in patients given a parenteral feeding regimen containing Liposyn II 20 percent or Liposyn III 2 percent.
Inclusion criteria: inclusion criteria

 Concurrent Medication:

 Allowed:

 All drugs used for the standard treatment of Pneumocystis carinii pneumonia (PCP).

 Other drugs for treatment of other AIDS conditions if they have been started more than 3 months prior to study entry.

 Patients must have:

 Diagnosis of AIDS.

 Weight loss > 10 percent of premorbid body weight.

 First or second episode of acute Pneumocystis carinii pneumonia (PCP).

Exclusion criteria:

 Co-existing Condition:

 Patients with the following conditions or symptoms are excluded:

 Do Not Resuscitate (DNR) status.

 Biliary stasis.

 Patients with the following are excluded:

 Do Not Resuscitate (DNR) status.

 Biliary stasis.

 Prior Medication:

 Excluded within 3 months of study entry:

 Immunomodulators.

 Antiviral new DT


Contrast Enhanced Ultrasound For The Evaluation Of Focal Liver Lesions

Summary: The aim of the study is to assess the value of contrast enhanced ultrasound in the evaluation of de novo focal liver lesions in clinical practice, in a prospective multi-center design.
Inclusion criteria: inclusion criteria:

 patients diagnosed with de novo FLL at standard ultrasound

 age > 18 years, male and female gender

 informed consent for the contrast enhanced study

Exclusion criteria: :

 patients with contraindication for contrast enhanced study: subjects with acute cardiac infarction, with class III/IV cardiac insufficiency, with rhythm disorders and pregnant women

 Patients diagnosed with simple cysts at standard ultrasound (biliary of hydatid)

 Patients with known FLL, for example after percutaneous treatment, in which the contrast study is used for the follow up of the patient.

['Focal Nodular Hyperplasia of Liver', 'Toxic Liver Disease With Focal Nodular Hyperplasia', 'Liver Metastases']


Evaluation of the High Dose Vitamin D3 Supplementation Effect and Influence of Polymorphism VDR Gene on Oxidative Stress and Inflammatory Process in Elderly

Summary: A vitamin D3 high dose would act as an antioxidant and anti-inflammatory improving markers of oxidative stress and inflammation in the elderly. Seniors exhibiting polymorphism in the VDR gene would become non-responsive to supplementation.
Inclusion criteria: inclusion criteria:

 Aged 60 years; diagnosis of failure / vitamin D, preserved cognitive status, disability accepting participate and are not included in any of the
Exclusion criteria:


Immunogenicity and Safety of a Booster Dose of Monovalent Glycoprotein-Conjugated (Diptheria Toxin -CRM197) Hib Vaccine in 365-569 Days Old Healthy Infants

Summary: This study will evaluate the safety and immunogenicity of booster dose of two commercially available vaccines used to prevent Haemophilus influenzae type b infections in children 365-569 days of age
Inclusion criteria: inclusion criteria:

 Infants 365-569 days of age.

Exclusion criteria: :

 Subjects who already received a booster dose of Hib vaccine.

 History of serious reaction(s) following vaccination.

 Any vaccination within 7 days of study vaccination.

 Known or suspected immune impairment.

['Haemophilus influenzae type b (Hib) vaccine']

['Haemophilus Influenzae Type b (Hib) Infection']


Efficacy Study of Quetiapine Plus Topiramate for Reducing Cannabis Consumption and Bipolar Mania

Summary: The objectives of this study are to determine whether this treatment may be useful for reducing cannabis consumption; reducing symptoms of bipolar mania; and weight mitigation therapy for individuals on psychopharmacotherapy.
Inclusion criteria: Inclusion/
Exclusion criteria:  inclusion criteria: To be included, all subjects must…

 have an authorized parent/legal guardian who understands the nature of the study and who provides written informed consent if the study subject is younger than 18 years of age. Additionally, each subject must provide assent to the study;

 be fluent in English;

 be 12 to 21 years of age, inclusive;

 be using a medically accepted means of contraception (i.e., oral contraceptives and barrier methods (diaphragm or condom), medroxyprogesterone acetate injectable suspension, abstinence) if female and of menarche. Oral contraceptives alone are not acceptable means of contraception because concomitant use of topiramate and low estrogen oral contraceptive pills may lead to oral contraceptive failure;

 have a diagnosis of bipolar I disorder in a current manic or mixed episode, in addition to a cannabis use disorder (which includes abuse or dependence) within 28 days prior to screening, as determined by the WASH-U-KSADS;

 have an initial YMRS total score of >16 at screening and baselines;

 use cannabis a minimum of twice per week on average during the 28 days prior to screening.

['Quetiapine and placebo', 'Quetiapine and Topiramate']

Quetiapine and placebo
Quetiapine and Topiramate

['Bipolar Disorder', 'Cannabis-Related Disorder']

Bipolar Disorder
Cannabis-Related Disorder


Melatonin for Sleep in Children With Autism

Summary: The purpose of this study is to determine if liquid supplemental melatonin is an effective treatment for children with autism who have sleep problems related to insomnia (difficulty falling asleep).
Inclusion criteria: inclusion criteria:

 Children with autism ages 4-10 years.

 Diagnosis of autism based on Autism Diagnostic Observation Schedule (ADOS).

 Time to fall asleep of 30 minutes or longer by parent report at least 3 nights/week in the last 3 months.

 Children may take seasonal allergy medications.

 Children may take the following medications for the same dose at least 3 months: Citalopram (Celexa), Escitalopram (Lexapro), Amphetamine-dextroamphetamine (Adderall), Atomoxetine (Strattera), Methylphenidate(Ritalin), Dextroamphetamine(Dexedrine), Risperidone (Risperdal.

Exclusion criteria: :

 Children taking medications other than those in the inclusion criteria.

 Children with primary sleep disorder other than insomnia (such as sleep-disordered breathing).

 Children with non-febrile unprovoked epileptic seizure within the last two years.

 Children with liver disease or high fat diets, as melatonin metabolism may be affected in these children.

 Children who are visually impaired (partially or completely blind) as light suppresses melatonin synthesis and these children may have altered diurnal melatonin rhythms.

 Children with known genetic syndromes co-morbid with autism including fragile X, Down syndrome, neurofibromatosis, or tuberous sclerosis.

 Children who have outside normal limits on blood work for complete blood count, liver and renal function and hormone levels of ACTH, cortisol, LH, FSH, prolactin, testosterone and estradiol.

 Tanner staging beyond level 1 at any time point in the study.

 Children whose assessment score does not place them on the autism spectrum.

['supplemental liquid melatonin', 'flavored liquid or liquid supplemental melatonin']


Off- Loading Shoe to Improve Healing and Prevention of Recurrence of Neuropathic Diabetic Plantar Foot Ulcers

Summary: It's a pilot prospective opened multicentric randomised study. We measure the efficiency and the safety of a new concept of off-loading shoe (SANIDIAB) compared with an old one (BAROUK) to treat chronic diabetic foot ulcer which involved a high risks of amputation 64 diabetic patients with a plantar neuropathic ulcer of the fore foot without infection, osteomyelitis or angiopathy, will be included. 32 patients will be treated with SANIDIAB shoe and 32 with BAROUK shoe
Inclusion criteria: inclusion criteria :

 More of 18 years old man or woman

 Type 1 or 2 Diabetes mellitus

 A new plantar ulcer of the fore foot or the toes

 GRADE 1A or 2 A of the University of Texas Classification

 Neuropathy assessed by absence of sensation in 10g monofilament test

Exclusion criteria:

 Severe angiopathy (Grade 3 of the PEDIS classification)

 Osteomyelitis or cellulitis of the foot

 Transmetatarsal amputation

 Other study in course

 Immunosuppressive drugs, antibiotic therapy,

 Hepatic insufficiency

 No possibility to follow the patients every 14 days

 No state health insurance

 Pregnancy

['Diabetes Mellitus', 'Diabetic Neuropathic Foot Ulcer']

Diabetes Mellitus
Diabetic Neuropathic Foot Ulcer


Early Detection of Anaemia During the Maternity

Summary: Estimate the efficiency of a strategy of premature screening of the maternal anaemia during the first quarter of pregnancy versus the usual strategy of screening of the anaemia during the sixth month.
Inclusion criteria: inclusion criteria:

 Every patient followed at the HME at the beginnig of the pregnancy

Exclusion criteria: :

 pregnency women who don't speak french

 pregnancy women affected by béta thalassemia

 pregnancy woman having had a périconceptionnel treatment against the anaemia


Comparison of Resin Salve and Octenidine in Patients With Neuropathic Diabetic Foot Ulcers

Summary: Prevalence of diabetic foot ulcers are reported to be 15% in patients who suffer from diabetes and ulcerations are present in 84% of all diabetes-related amputations. Peripheral neuropathy leading to unperceived trauma seems to be the major cause of diabetic foot ulcers with 45-60% of ulcers to be considered merely neuropathic and 45% of mixed, neuropathic and ischemic etiology. Ulceration of lower limb is one of the most common complications related with diabetes and one of the major causes for hospitalization of diabetic patients. The most significant contributors to diabetic lower limb ulceration are neuropathy, deformity, uncontrolled elevated plantar pressure, poor glycemic status, peripheral vascular disease, male gender and duration of diabetes. Treatment of lower limb ulcers imposes an enormous burden on health care resources worldwide, and at least 33% of all expenses are spent to treat diabetic ulcers manifested as a complication of diabetes.~Although at least 170 topical wound care products are available, evidence of the superiority of one over another is tenuous, well-designed randomized, controlled trials are rare, and the number of case-control or observational studies is limited. In recent years, salve prepared from Norway spruce (Picea abies) resin has successfully been used in medical context to treat both acute and chronic wounds and ulcers of various origins. The objective of this prospective, randomized and controlled clinical trial is to investigate healing rate and healing time of neuropathic diabetic foot ulcer in patients, who are suffering from infected fore- or mid-foot ulceration (PEDIS-classification ≥ Grade II; 19) originated from Type I or II diabetes, and in patients whose diabetic ulcerations are candidates for topical treatment with resin (Study treatment) or octenidine (Control treatment). In addition, factors contributing with delayed healing of ulceration, antimicrobial properties, safety and cost-effectiveness of the resin salve treatment and control treatment will be analyzed.
Inclusion criteria: inclusion criteria:

 an adult patient (18-80 years) suffering from infected neuropathic fore- or mid-foot ulceration originated from type I or II diabetes (PEDIS-classification ≥ Grade II).

Exclusion criteria: :

 a patient whose life expectancy is less than 6 months

 an ulceration of ischemic or neuroischemic origin

 presence of systemic inflammatory response signs

 heel ulceration

 presence of osteomyelitis

 pregnancy

 known hypersensitivity to any of the ingredient including in the study or control treatment products

 a patient who is unable to give informed consent

 a patient who has an advanced malignant disease.

['Resin salve treatment', 'Octenidine treatment']

Resin salve treatment
Octenidine treatment

['Diabetes Mellitus', 'Diabetes Complications', 'Diabetic Neuropathies', 'Wound Infection']

Diabetes Mellitus
Diabetes Complications
Diabetic Neuropathies
Wound Infection


Inhalation Profiling of Idiopathic Pulmonary Fibrosis (IPF) Patients

Summary: This is a clinical study to characterise the lung function, airway morphometry, pharyngometry and inhalation profiles in patients with mild to severe Idiopathic Pulmonary Fibrosis (IPF) over a period of up to 6 months. Inhalation profiles will be recorded from patients with IPF as they inhale during tidal breathing, and following two sets of instructions (maximal effort and 'long, steady and deep' inhalation), across a range of airflow resistances that reflect those of typical inhalers used to deliver medication to the lungs. Mouth and throat dimensions will be measured using an acoustic reflectance Pharyngometer. Measurements of lung function will be made using conventional sprirometry, plethysmography and diffusion, whilst Low Dose High Resolution Computed Tomography (HRCT) will be used to scan the airways at two lung volumes; functional residual capacity (FRC) and total lung capacity (TLC). Data from HRCT will be used to reconstruct airway morphometry, and model inhaled particle deposition within the lung. Overall, the study allows a further understanding of the IPF patient population, using the data to assist in the development of new inhaled products for this disease. Following up the patients with additional HRCT scans at 3 and 6 months will enable the sensitivity of CT based criteria of disease progression to be compared with lung function criteria. No investigational product will be used in this study.
Inclusion criteria: inclusion criteria:

 Males/females aged 40 years and over, at the time of signing the informed consent.

 A female patient is eligible to participate if she is of: Non child-bearing potential, where females are post-menopausal, defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milliinternational units per milliliter (MlU/mL) and estradiol < 40 picograms per mililiter (pg/mL) (<147 pmol/L) is confirmatory. Peri-menopausal or pre-menopausal, and have a negative pregnancy test as determined by serum or urine human chorionic gonadotropin (hCG) test, confirmed at screening, and then at each subsequent clinic visit before the CT scanning is conducted.

 BMI within the range 18 - 32 kilogram per meter^2 (kg/m^2) (inclusive).

 Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

 Patients will have a diagnosis of IPF as determined by a responsible and experienced Respiratory physician and based on established criteria defined by the American Thoracic Society/European Respiratory Society: American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias.

 Patient's lung function measurements of Forced vital capacity (FVC) and Diffusing capacity of the Lung for Carbon Monoxide (DLCO) at screening must fall within the category below to be included in this study: FVC >=40 % predicted and DLCO >=30 % predicted.

Exclusion criteria: :

 Patients with a current Idiopathic Pulmonary Fibrosis (IPF) exacerbation.

 Patients with a known underlying cause of pulmonary fibrosis.

 Patients that have both IPF and Chronic obstructive pulmonary disease (COPD) that requires therapy with more than an intermittent bronchodilator or a long acting muscarinic antagonist, or where the Forced Expiratory Volume in One Second (FEV1)/ Forced vital capacity (FVC) ratio is <0.65.

 Patients with an upper or lower respiratory tract infection within four weeks of Visit 1.

 Patients with a recognised co-existing respiratory disorder other than usual interstitial pneumonia (UIP) (e.g. significant COPD, asthma, sarcoid, lung carcinoma) that in the opinion of the investigator would confound the study outcomes.

 Patients with poorly controlled left ventricular heart failure.

 Serious or uncontrolled medical, surgical or psychiatric disease that in the opinion of the investigator would compromise patient safety or confound the study data (e.g. congestive cardiac failure [CCF], asthma, angina, neurological disease, liver dysfunction and blood dyscrasia).

 Patients found to have clinically significant anaemia until adequately treated.

 Patients that have a history of alcohol abuse.

 Patients who are currently taking Pirfenidone for IPF or who have received Pirfenidone within the previous 30 days prior to Visit 1.

 Patients with previous exposure to ionising radiation > 5 millieSievert (mSv) in the 3 years prior to enrolment (not including ionising radiation used for therapeutic or diagnostic purposes or for purposes that involve patient benefit).

 Patients who have a history of claustrophobia.

 As a result of the medical history, physical examination or screening investigations, the physician responsible considers the patient unfit for the study.

 The patient is unable or unwilling to perform study assessments and procedures correctly.

 The patient has received an investigational drug for IPF within 30 days of the start of the study.

 A requirement for long-term oxygen therapy (LTOT) as defined by the prescription of oxygen to be used for greater than or equal to 12 hours of therapy per day. Note - short burst oxygen therapy is permitted.

 Patient is kept under regulatory or judicial order in an institution.

 Patient is mentally or legally incapacitated.

['Assessment of Idiopathic Pulmonary Fibrosis over a period of up to 6 months']


Olanzapine Versus Lithium in the Treatment of Acute Depression in Patients With Bipolar II or Bipolar Not Otherwise Specified(OL Study)

Summary: Determine the efficacy and tolerability of olanzapine for treatment of acute depression in patients with bipolar II or bipolar disorder NOS compared with lithium.
Inclusion criteria: inclusion criteria:

 major depressive episode in type2 bipolar disorder or bipolar disorder NOS.(MADRS more than 20 point)

 18years to 65years

 subjects who sign the informed consent document

Exclusion criteria: :

 don't have Diabetes and abnormal metabolism of sugar

 not noticed as bipolar disorder

 have an organic brain disease

 pregnant or breastfeeding women

 don't have heart disease

 have actively suicidal thought(Suicidal ideation score of MADRS is 6)

 who are judged by the investigator to should be excluded from the study