The Effect of Exercise on Stem Cell Mobilization and Heart Function in Patients Undergoing Cardiac Rehabilitation

Summary: This study will look at the effect of a cardiac rehabilitation exercise program on release of stem cells from the bone marrow and on heart function. Stem cells are primitive cells produced and released by the bone marrow, circulate in the bloodstream and develop into white blood cells, red blood cells and platelets. Some stem cells may also develop into other kinds of cells, including those that make up heart muscle, especially if the heart has been damaged or is not getting sufficient blood. Stem cells called endothelial progenitor cells (EPCs) are thought to form new blood vessels that can carry blood to areas of the heart muscle that are oxygen-deprived because of clogged arteries. Previous experiments have shown that some EPCs can be forced out of the bone marrow by exercise. This study will examine whether repeated exercise and lifestyle changes increase the number of EPCs released into the bloodstream and if these cells improve heart and blood vessel function.~Patients 21 years of age and older with coronary artery disease may be eligible for this study. Candidates will be screened with a medical history and physical examination, including a cardiovascular evaluation, and blood tests. The participants will be enrolled in a 2- to 3-month cardiac rehabilitation program that includes 24 to 36 60-minute sessions of exercise, plus instruction on lifestyle changes related to diet, stress management, and relaxation techniques. In addition, participants will undergo the following tests and procedures:~Brachial reactivity study: This test measures how well the arteries widen. The patients rest for 30 minutes, and then an ultrasound device is placed over the artery just above the elbow. The device measures the size of the artery and blood flow through it before and after the patient is given a spray of nitroglycerin under the tongue.~Blood tests for EPC levels and genetic testing: These measure EPCs and determine whether certain genes that may regulate EPC function are turned on or off. Genes are made up of DNA, the molecules that lead to the production of proteins by cells. Some of these proteins may be important in releasing EPCs from the bone marrow to travel in the bloodstream to the heart and repair blood vessels and muscle cells.~Treadmill exercise testing: Patients exercise on a treadmill with continuous monitoring of the heartbeat and frequent measurements of oxygen saturation, using a finger clip device. The patient continues to exercise until moderate chest pain, shortness of breath, or fatigue develops.~Questionnaire: Patients fill out a 15-minute questionnaire about their general physical and mental health status at the first and last visits to the clinic.~Magnetic resonance imaging (MRI) of the heart: Patients who are eligible to undergo MRI have this test twice during the study, once before beginning the rehabilitation program and again after completing the program. The MRI shows heart function and blood flow in the heart. For this test, the patient lies on a stretcher inside a long narrow cylinder (the scanner). During the scan, the drug dipyridamole, which increases blood flow to the heart, is infused into a vein of the hand or arm. Another drug, gadolinium, is also infused to brighten the images produced.
Inclusion criteria: inclusion criteria:

 Adults older than 21 years.

 Coronary artery disease established by angiography.

 No myocardial infarction within 1 month.

 Left ventricular ejection fraction greater than 30%.

 No congestive heart failure symptoms within 2 months.

 No medical condition that might prohibit safe participation in cardiac rehabilitation.

 Subject understands protocol and provides written, informed consent in addition to willingness to comply with specified follow-up evaluations.

Exclusion criteria: :

 Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.

 Angina pectoris that is prolonged in duration (greater than 20 minutes), or does not respond to nitroglycerin (2 tablets).

 Subject physically unable to perform cardiac rehabilitation protocol due to neurologic or orthopedic conditions.

 Hypersensitivity to organic nitrates.

 Women of childbearing age unless recent pregnancy test is negative.

 Lactating women.

 Known hypersensitivity to dipyridamole or to gadolinium if patient eligible for MRI study.


How the Loss of Dopamine and Dopamine-Restoring Medicines Affect Movement Performance

Summary: This study has two purposes: 1) to understand the effect of a decline of dopamine in the brain during normal aging and in patients with Parkinson's disease, and 2) to investigate how medicines used to treat Parkinson's disease improve movement performance in patients.~Patients with Parkinson's disease have difficulty performing precise finger movements, mainly because of a dramatic decrease of a substance called dopamine in parts of the brain. Medicines such as levodopa, which help restore dopamine levels, can greatly improve function; however, little is known about how these drugs work. In normal aging, dopamine decreases slightly in certain parts of the brain, but the importance of this decline is poorly understood. This study may provide new information about Parkinson's disease and normal aging that might lead to better treatment strategies.~Patients with mild to moderate Parkinson's disease and healthy volunteers 21 years of age and older may be eligible for this study. All participants must be right-handed. All candidates will be screened with a medical history and physical and neurological examinations, including memory tests and mood examination.~Brain function will be studied using functional magnetic resonance imaging (fMRI) study and positron emission tomography (PET). Participants may be asked to stop using medications that can affect the central nervous system, such as sleeping pills or drugs for depression or anxiety, for 1 week before each study visit. Patients with Parkinson's disease may also be asked to stop using antiparkinsonian medications at least 12 hours before each visit. In addition, all participants will be asked to abstain from alcoholic beverages at least 24 hours before the fMRI and PET scans, and from nicotine and caffeine for at least 12 hours before the scans.~Participants will have fMRI, which uses a strong magnetic field and radio waves to create images of the brain. The subject lies on a table in a tunnel-like cylinder (the scanner) for 1 to 2 hours, lying still for 5 to 15 minutes at a time. He or she can communicate with the technician or researcher at all times during the test through an intercom system. Scans will be done while the subject is at rest and while he or she is performing finger movements. The movements involve pushing five buttons on a box-each button every 3 seconds on average in a specific order. Patients with Parkinson's disease will be studied off- and then on- medications that restore the levels of levodopa in the brain.~Some participants may be asked to undergo a PET scan on a separate visit. A PET scanner is a doughnut-shaped machine similar in appearance to a CT (computed tomography) scanner. PET scans detect radioactivity used to provide information on brain activity. Before the test begins, subjects are given a dose of carbidopa-a medicine that increases the amount of levodopa in the brain. A catheter (thin, plastic tube) is then inserted into an arm or wrist vein, and a radioactive form of levodopa called 18Fluorodopa is injected through the catheter. A moldable plastic mask with large openings for eyes, nose, and mouth is placed on the face to help keep the head still during scanning. The total scan time is 2 hours or less.
Inclusion criteria: inclusion criteria:

 We will only include PD patients with a stable clinical response to L-DOPA and DAergic agents.

 We will only recruit patients with early or mild-to-moderate PD (score on Hoehn & Yahr scale 148 less than 3).

 To obtain a homogeneous group, the PD cohort will comprise only non-demented, non-depressed, with parkinsonian symptoms and signs primarily akineto-rigid.

 If resting tremor is present, only patients with mild or moderate tremor (UPDRS tremor ratings 1 or 2 in the right upper limb) will be included in the study.

 Our group of healthy volunteers will include the following age range: 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and 70 years and over.

 Research subjects may be male or female and they must be right-handed.

 Pregnant women will not participate in the study.

 Research subjects will be asked to refrain from caffeine and nicotine for at least 12 hours and to abstain from alcohol at least 24 hours before the fMRI.

Exclusion criteria: :

 Subjects belonging to one of the following groups will be excluded from the study:

 Subjects with a familial history of PD.

 Patients with a marked resting tremor (score at the UPDRS scale above 3 in the right upper limb).

 Patients with a score at Hoehn & Yahr scale equal or above 3.

 Patients with progressive neurological disorders other than PD.

 Subjects with cognitive impairment (i.e., score on Mattis scale below 123/144).

 Subjects with significant mood disturbances (i.e., score on BDI scale above 10).

 Subjects with abnormal MRI findings at visual inspection (prominent normal variants such as mega cisterna or cavum septum pellucidum, signs of severe cortical or subcortical atrophy, brain tumors, vascular diseases, trauma or AVMs).

 Subjects with a history of significant medical disorders, or requiring chronic treatment with other drugs that cannot be stopped.

 Subjects with prior exposure to neuroleptic agents or drug use.

 Subjects with significant past and present history of hypertension, cardiovascular disease and diabetes mellitus.

 Subjects with severe orthopedic or rheumatologic pathology of the right upper limb.

 Subjects with past or present neuropsychiatric illness, head trauma with loss of consciousness, epilepsy, cerebro-vascular disease, past and present history of alcohol or substance abuse, including cigarettes, medical conditions that may alter cerebral functioning

 Subjects with cancer.

 Subjects who have pacemakers, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including heart valves and cochlear implants) or shrapnel fragments.

 Subjects incapable of giving an informed consent.

 Subjects with a positive pregnancy test.

 Subjects with pre-existing eyes condition.

 Subjects who are unable to tolerate being off of antiparkinsonian medications for 12 hours.

 Children will be excluded from the study because PD is infrequent before age 30.


Belimumab Assessment of Safety in SLE

Summary: The purpose of this study is to further enhance the existing knowledge regarding the side effects of belimumab when given with other lupus medicines to adults with active systemic lupus erythematosus (SLE). This study mainly focuses on collecting information on serious events that are not that common or may only be seen with long-term treatment. These events include death, serious infections and other infections of interest, cancers, serious mental health problems, including depression and suicide, and serious infusion and hypersensitivity reactions. This study is being done to help understand if treatment with belimumab increases the risk for these types of events. This study will also see if patients receiving belimumab with other lupus medicines can reduce their use of steroids, such as prednisone, over 1 year.
Inclusion criteria: Key inclusion criteria:

 Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria.

 Active SLE disease.

 Autoantibody-positive.

 On stable SLE treatment regimen which may include corticosteroids (for example, prednisone), antimalarial (for example, hydroxychloroquine) and/or immunosuppressants (for example, azathioprine, methotrexate, mycophenolate).

 Key
Exclusion criteria: :

 Pregnant or nursing.

 Have received treatment with any of the following: belimumab, either as a marketed product or as an investigational agent; any B cell targeted therapy (for example, rituximab) in the past year; or any biological agent (for example, adalimumab, etanercept, infliximab, or anakinra) in the past 90 days.

 Have received a live vaccine within the past 30 days.

 Have severe active lupus kidney disease.

 Have severe active central nervous system (CNS) lupus.

 Current or past positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

['Placebo plus standard therapy', 'Belimumab 10 mg/kg plus standard therapy', 'Standard therapy']


Long-term Immunogenicity of a HPV Vaccine in SLE

Summary: To study the 5-year immunogenicity against a quadrivalent HPV vaccine in patients with SLE and healthy controls.
Inclusion criteria: inclusion criteria:

 SLE patients

 Female patients aged 18-35 years

 Fulfilling the American College of Rheumatology (ACR) criteria for the classification of SLE

 Having participated in the investigators' original HPV study in 2010

 Able to give written informed consent

 Controls

 Women aged 18-35 years, matched those of SLE patients recruited

 No known chronic medical diseases

 Having participated in our HPV study in 2010
Exclusion criteria:


Bioequivalence Study of Zolpidem Tartrate Tablets and Ambien® Under Fasting Conditions

Summary: The purpose of this study is to compare the bioequivalence of a test formulation of zolpidem tartrate tablets to an equivalent oral dose of the commercially available reference drug product Ambien® (zolpidem tartrate tablets) in adult subjects under fasted conditions.
Inclusion criteria: inclusion criteria:

 Sex: Male or Female; similar proportions of each preferred

 Age: At least 18 years

 Weight: must be 15% of ideal weight for height and frame

 Subjects must be in good health and physical condition as determined by medical history

 Subjects must read and sign the Consent Form

Exclusion criteria: :

 History of treatment for alcoholism, substance abuse, or drug abuse within past 24 months.

 History of malignancy, stroke, diabetes, cardiac, renal or liver disease, or other serious illness.

 History of GERD, malabsorption syndrome, colon cancer, or chronic colitis, including Crohn's disease.

 History of treatment for asthma within the past five (5) years.

 History of mental depression.

 History of pulmonary disease.

 History of sleep apnea.

 Females who are pregnant or lactating.

 History of hypersensitivity to zolpidem tartrate, or any hypnotic or sedative.

 Treatment with any other investigational drug during the four weeks prior to the initial dosing of the study.

 Donation of blood within four weeks prior to the initial dosing of the study

 Smokers or subjects who use tobacco/nicotine products. Three months abstinence is required.

['Zolpidem Tartrate 10 mg tablet', 'Zolpidem Tartrate 10 mg tablet (Ambien®)']


A Comparative Study Between a Pre-hospital and an In-hospital Circulatory Support Strategy (ECMO) in Refractory Cardiac Arrest (APACAR2)

Summary: Cardiac arrest (CA) affects approximately 40,000 people in France. It is still a major cause of death in a young population. Management of CA is defined by international recommendations, detailed by learned societies in each country. It includes several links that are interconnected for its optimisation. Despite all these improvements, no progress, or little has been made in the survival of CA victims over the past few years in industrialised countries, and the survival rate in France is 3% to 5%.~Refractory cardiac arrest is defined as failure, after 30 minutes of specialised resuscitation. It used to be the standard to admit that there was no hope of spontaneous cardiac activity and satisfactory neurological recovery after this period, except in cases of CA with neuroprotection (intoxication, hypothermia).~External circulatory support such as extracorporeal membrane oxygenation (ECMO) makes it possible to replace the circulatory activity of the myocardium and the respiratory activity of the lungs.~In in-hospital cardiac arrest (CA) some teams use ECMO with an improvement in the survival rate of 20% in comparison to standard resuscitation. This use demonstrates the possibility of neurological recovery independent of the recovery of spontaneous cardiac activity which can be differed.~These results encouraged the use of ECMOs in cases of out-of-hospital refractory cardiac arrests. Patients who are victims of CA are resuscitated for 30 minutes on the spot where the CA occurs. They are then transferred to a specialised centre. The significant improvement in survival noted in in-hospital CAs was not observed in the French series of studies concerning out-of-hospital CAs. This survival is currently estimated at 4%. This difference can be partly explained by the difference in time between the beginning of cardiac massage and the implementation of circulatory support by ECMO (low flow period). This time period is directly correlated to survival.~To demonstrate the superiority of this strategy in terms of survival, investigators would like to conduct a randomised comparative study of two strategies: 1) installation of an ECMO between the 20th minute to the 30 minute of CA, directly at the site of the CA, by emergency physicians and/or specifically trained resuscitators 2) On-site resuscitation optimised with secondary transfer to the hospital for the implementation of support. The purpose is to increase by 5% to 20% the survival of victims of out-of-hospital refractory cardiac arrests with a good neurological prognosis.~Main objective:~The hypothesis is that pre-hospital ECMO will result in survival for 20% of the patients, considering that the percentage of survival with in-hospital ECMO is less than 5%.~Main judgement criterion:~Survival with good neurological outcome (CPC 1 or 2) on discharge from intensive care or at 6 months~Secondary judgement criteria:~Success rate of the implementation of ECMO ECMO implementation time Immediate complications: haemorrhage, infection Number of organ harvesting The quality of survivors' neurological status according to the CPC neurological classification at D 28, 2 months and 1 year Predictive indicators of the prognosis during cardiac arrest via cerebral and biological monitoring Methodology, type of study: This is a prospective randomised study of current care Sample size (SS, power, risk): A total number of 105 patients in each group will make it possible to demonstrate at the alpha risk of 5% and a power of 1-β=90%, a significant difference in favour of early pre-hospital ECMO compared to the current practice with in-hospital ECMO.
Inclusion criteria: inclusion criteria:

 Eligible patients have the following combination of criteria:

 Adults over 18 years of age and under 65 years of age

 And Refractory cardiac arrest (defined by the failure of professionals to resuscitate at the 20th minute of cardiac arrest with a minimum of 3 Automatic External Defibrillator (AED) or equivalent analyze

 And Beginning of external cardiac massage within the first 5 minutes after cardiac arrest (no flow < 5 min.) with shockable rhythm or the presence of signs of life during resuscitation (any rhythm): spontaneous movement, absence of mydriasis and/or pupillary response, spontaneous breathing movements

 And Medical cause of the cardiac arrest

 And End-Tidal CO2 (ETCO2) above 10 mm Hg at the time of inclusion

 And Absence of major co-morbidity. And Extra-corporeal Membrane Oxygenation (ECMO) team available and on-site before the 40th minute

Exclusion criteria: :

 Children under 18 years of age

 Adults over 65 years of age

 Period of more than 5 minutes without cardiac massage after collapsing

 Known co-morbidity that compromises the prognosis for short or medium-term survival

 Cardiac arrest during transportation times

['ECMO Insertion on pre hospital setting', 'In Hospital ECMO']

ECMO Insertion on pre hospital setting
In Hospital ECMO


Vocal Acoustic Biomarkers in Depression

Summary: This Phase II SBIR study will replicate pilot study methods establishing computer-automated methods for assessing depression severity using interactive voice response system technology and demonstrating feasibility of obtaining measures of depression severity and treatment response through vocal acoustic analysis of speech samples obtained over the telephone. The study will automate vocal acoustic analysis methods, evaluate applicability to other patient populations (non-English speakers, children/young adult, and geriatric), and further develop multivariate acoustic models to enhance biomarker sensitivity to treatment response and prediction of the response likelihood for individual patients.
Inclusion criteria: inclusion criteria:

 Age 18 - 80.

 Written informed consent.

 Current MDD according to the fourth version of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV)

 Recently started to receive or about to start receiving treatment for MDD

 Quick Inventory of Depressive Symptomatology - Clinician-Rated (QIDS-C) and QIDS-IVR scores equal or greater than 10 at baseline visit.

Exclusion criteria: :

 Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment.

 History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, patients with substance dependence disorders, other than alcohol, active within the last 12 months.

 History or current diagnosis of dementia.

 Diagnosis or history of hypothyroidism.


Sleep-disordered Breathing in Eisenmenger Syndrome

Summary: Sleep-disordered breathing (SDB) is a wellknown comorbidity in cardiovascular disease. Knowledge about SDB in adult congenital heart disease is limited.
Inclusion criteria: inclusion criteria:

 Eisenmenger Syndrome (definition: Pulmonary ≥ systemic vascular resistance with pulmonary-to-systemic shunt and cyanosis (periphery oxygen saturation < 92% at rest and/or < 87% during exercise).

 Stable for ≥ 3 months (no hospitalization, no change of medication, no deterioration).

Exclusion criteria: :

 Down's syndrome.

 Iron deficiency (definition: Ferritin < 12 µg/l and/or transferring saturation < 20%).

 Regular phlebotomy.

 Suspicion of risk of non-compliance.

['Eisenmenger Syndrome', 'Congenital Heart Disease', 'Sleep-disordered Breathing']

Eisenmenger Syndrome
Congenital Heart Disease
Sleep-disordered Breathing


Brief Tobacco Cessation Intervention

Summary: Traditional smoking cessation clinics and telephone quitlines are expensive and 'passive' as they require motivated smokers to visit the clinic or make a phone call to seek help. However, in most middle-resource countries, smoking cessation clinics are not well publicized. Most health care professionals (HCP) are not active in performing smoking cessation counselling to their patients. They are not aware of the available smoking cessation services or the benefits of such services and hence do not refer smokers to smoking cessation services. On the other hand, physicians play a critical role in reducing tobacco use by advising smoking patients to quit (Richmond, 1999). Physician's advice to quit smoking not only motivates smokers to quit but also increases their quitting confidence (Fiore et al., 2000; Ossip-Klein et al., 2000).~Brief smoking cessation interventions have been shown to be effective with strong evidence from randomized controlled trials (RCTs), however, it is no evidence to show that longer interventions are more effective than shorter interventions. If carried out in routine clinical practice by all physicians and other HCP, brief interventions can potentially benefit a great number of smokers and increase smoking cessation rate. Therefore, we propose to examine the effect of a brief smoking cessation counselling intervention (10-20 seconds AWARD model) among patients using a randomized controlled trail (RCT) design in Guangdong province, China~This project aims to evaluate the effect of physicians' brief smoking cessation intervention (AWARD model) in real busy clinic settings using a randomized controlled trial (RCT) design.
Inclusion criteria: inclusion criteria:

 Outpatients aged 18 years or above

 Smoke on at least 1 day in the past 30 days

 Chinese residents able to communicate in Chinese (Mandarin or Cantonese)

 Has a telephone

Exclusion criteria: :

 Smokers currently receiving smoking cessation interventions

 Smokers currently enrolled in other smoking cessation trials

 Smokers who need special care on quitting and are not suitable for AWARD intervention (determined by his/her doctor)

 Smokers with communication difficulties (physical or cognitive condition)

['The brief smoking cessation AWARD model', 'Placebo intervention']

The brief smoking cessation AWARD model
Placebo intervention


Exploring the Effectiveness of the 'Back of the Net' Intervention on Indices of Physical and Psychological Measures

Summary: To date very little research has focused on the mental health of young men. The main aim of the proposed research is to explore the effectiveness of a combined exercise and internet-based cognitive behavioral therapy (CBT) intervention (called Back of the Net) on indices of suicide risk in young men. A second aim is to explore the relationship between physical self-concept, self esteem, body fat composition, body circumference and changes in depression as a result of an exercise intervention. It is hypothesised that the combined exercise and internet-delivered CBT intervention will have greater benefits for indices of suicide risk compared to an exercise-only intervention, an internet-delivered CBT-only intervention and a control condition.
Inclusion criteria: inclusion criteria:

 Healthy males aged 18-40 years

 Available twice a week for 10 weeks and willing to participate in moderate intensity exercise for 50 minutes at each session

 Not regularly physically active (i.e., engages in a structured exercise session once or less per week)

 Willing to participate in the internet-based CBT intervention once per week for 10 weeks

Exclusion criteria: :

 Current illness or history of clinical conditions that prevents participation in exercise

 Currently alcohol/drug abusing

 Major cognitive or psychiatric impairments

 Currently receiving medication for major psychiatric disorders, including depression

['Exercise', 'Online Cognitive Behavioural Therapy']

Exercise
Online Cognitive Behavioural Therapy

['Self Concept', 'Body Fat Composition', 'Depression', 'Perceived Social Support']

Self Concept
Body Fat Composition
Depression
Perceived Social Support


PACIFIC: Providing Adults Collaborative Interventions For Ideal Changes

Summary: The objective of this proposed study is to collect initial efficacy data on ROC and ROC + BWL compared to an active comparator (AC) and to BWL.
Inclusion criteria: All participants will be between the ages of 18-65 meeting criteria for overweight, with a BMI between 25 and 45.

 Participants will provide written informed consent for study participation.

 Participants will possess English language skills at the 5th grade reading level.

 Participants will be free of major medical conditions such as a recent history of coronary heart disease; recent history of myocardial infarction; recent symptoms of angina, diabetes, recent stroke, orthopedic problems that would limit activity during the following twelve months; or any other serious medical condition that would make physical activity unsafe.

 Participants will not have bulimia or anorexia, significant cognitive impairment, a known psychotic disorder, or unstable psychiatric illness (e.g., recent psychiatric hospitalization, acute suicidal ideation) as derived from their intake interview and questionnaires.

 Participants will not be moving out of the San Diego area for the duration of their study enrollment (24 months).

 Participants will not be pregnant, planning to get pregnant in the 2 year study period or lactating.

 Participants will not be taking medication for weight loss or that may impair physical activity tolerance or performance.

 Participants with medical or psychological problems, or taking medications that could make adherence with the study protocol difficult or dangerous will not be included.

 Participants cannot have a history of bariatric surgery

 Participants cannot currently be enrolled in an organized weight control program.
Exclusion criteria:

['Regulation of Cues (ROC)', 'Behavioral Weight Loss (BWL)', 'BWL + ROC', 'Nutrition Education, Stress Management and Social Support']

Regulation of Cues (ROC)
Behavioral Weight Loss (BWL)
BWL + ROC
Nutrition Education
Stress Management and Social Support


Continuous Transcutaneous Electrical Stimulation in Sleep Apnoea

Summary: The aim of this randomized, double-blinded, sham-controlled cross-over trial is to demonstrate the effectiveness of continuous transcutaneous electrical stimulation of the pharyngeal dilator muscles to reduce sleep-disordered breathing.
Inclusion criteria: inclusion criteria:

 males and females, age >18years and <75years, body-mass index (BMI) >18 and <40kg/m2, non-smokers, sleep apnoea with an ODI ≥15/h or sleep apnoea with an ODI ≥5/h plus an Epworth sleepiness score >10.

Exclusion criteria: :

 morbid obesity (BMI>40kg/m2) or cachexia (BMI<18kg/m2), obesity-hypoventilation syndrome (total sleep time with oxygen saturation (SpO2) less than 90% of more than 10% of the night), active smokers or smoking history of >20pack years, acute or critical illness, acute psychosis or chronic mental disorder affecting capacity, previous home-mechanical non-invasive ventilation and metal implants in the upper part of the body (this excludes dental implants).

['Transcutaneous electrical stimulation', 'Sham stimulation']

Transcutaneous electrical stimulation
Sham stimulation


Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy

Summary: The aim of this study is to evaluate the effects of subantimicrobial dose doxycycline (50 mg/d), administered for 12 weeks, on patients with mild Thyroid-Associated Ophthalmopathy (TAO).
Inclusion criteria: inclusion criteria:

 Clinical diagnosis of Thyroid-associated ophthalmopathy

 Mild TAO

 Normal serum free thyroxine and free triiodothyronine concentrations

 No previous specific therapy for TAO, except for local measures

 Written informed consent is obtained

Exclusion criteria: :

 Pregnant females as determined by positive (serum or urine) hCG test at screening or prior to dosing, or lactating females

 Uncontrolled diabetes or hypertension

 History of mental / psychiatric disorder

 Hepatic dysfunction (Alb, AST, ALT and Alkaline phosphates levels must be within normal range for eligibility)

 Renal impairment (Urea and Creatinine levels must be within normal range)

 Tetracycline allergy or intolerance

['Graves Ophthalmopathy', 'Graves Disease', 'Thyroid-associated Ophthalmopathy', 'Thyroid Diseases', 'Endocrine System Diseases', 'Eye Diseases, Hereditary', 'Hyperthyroidism', 'Autoimmune Diseases', 'Immune System Diseases']

Graves Ophthalmopathy
Graves Disease
Thyroid-associated Ophthalmopathy
Thyroid Diseases
Endocrine System Diseases
Eye Diseases
Hereditary
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases


Analysis of Balance in the Aging Process

Summary: Introduction: While growing older, it is possible to notice a decrease in the functional and physiological reserves in the organism which impairs the the abilities in the elderly in doing some tasks. A simple balance becomes a challenge.~Objective: To evaluate the functional balance in the aging process.~Methods: The group was formed by 48 people from 10 to 85 years old. The evaluation instruments are the Berg Balance Scale (BBS), the Performance Oriented Mobility Assessment (POMA), the Unipodal Support Test, the Functional Reach Test and the Romberg's Test.
Inclusion criteria: inclusion criteria:

 Absence of the basic pathology that interferes directly in the balance

Exclusion criteria: :

 Neurological changes

 Cognitive impairment

 Orthopedic injury

 Use of orthoses for lower limb

 Obesity

 Exercise frequently (more than twice a week)

 The bearer of any commitment to stay in their standing position


Retrospective Study Evaluating The Current Utilization Of Desvenlafaxine Succinate Sustained-Release (Pristiq) Among Psychiatrists And Primary Care Physicians In The Treatment Of Patients With Major Depressive Disorder

Summary: The goal of this observational study is to learn about how Pristiq is currently being used in general practice and how psychiatrists and primary care physicians currently perceive Pristiq in terms of efficacy, tolerability, and adherence compared to other treatments for major depressive disorder (MDD).
Inclusion criteria: inclusion criteria:

 Patients must be adult, diagnosed with major depressive disorder and treated with pharmacotherapy.

 Physicians must be either a psychiatrist or a primary care physician, a prescriber of Pristiq, have at least 3 charts representing the 4 identified patient types, have been in clinical practice between 4 and 35 years, primarily office based (50%+), not participated in a research study relating to antidepressants or antidepressant therapy within the past month, not a consultant or have a professional relationship with a pharmaceutical company other than for clinical trials or speaking engagements, and not be employed by of affiliated with an advertising agency, market research company, or pharmaceutical company.

Exclusion criteria: :

 Patients who have not been treated for depression.

['Pristiq first-line treatment charts', 'Pristiq second-line treatment charts', 'SNRI or SSRI first-line treatment charts', 'SNRI or SSRI second-line treatment charts']


Validation of Digital Chest-X-ray (CXR) to Assess Lung Recruitment in ARDS

Summary: Lung recruitability is essential for optimal Positive end-expiratory pressure (PEEP) selection in ARDS patients. It is defined as the potential for the non aerated or poorly aerated lung mass to become aerated due to the increase in airway pressure. PEEP contributes to lung recruitment mostly by maintaining some amount of the end-inspiratory recruitment at the end of expiration. PEEP also stabilizes patency of the small airways and minimizes the repeated opening and closing of them during the breathing cycle, which is implicated in a further lung inflammation. The gold-standard method for assessing lung recruitability is lung CT scan. For economic and feasibility this technique cannot be used in routine. Therefore, techniques that can be used at the bedside to measure lung recruitability are very well known. The measurement of recruited lung volume (Vrec) by using pressure-volume curve generated by the ventilator is another reference method to approach lung recruitment. It can be done at the bedside. Chest-X-Ray (CXR) is an interesting option as done in routine in this setting. Furthermore, it allows quantifying aeration thanks numerical image processing and a regional approach. In a preliminary one-center study we found a significant negative correlation between the amount of Vrec and the reduction in lung density measured by digital CXR between 5 and 15 cm H2O PEEP. In present study we would like to extend this previous result on a larger number of patients in a multicenter investigation.
Inclusion criteria: inclusion criteria:

 intubation and mechanical ventilation in the ICU

 Ramsay score 6 under sedation and analgesia

 ICU respirator implemented with pressure-volume curve device

 age equal to or greater than 18 years

 ARDS defined from the Berlin criteria

 absence of pneumothorax on the CXR before the study

 Absence of pleural effusion greater than 500 ml estimated from ultrasonography.

 no child-bearing woman

 written inform consent signed by the next of kin

Exclusion criteria: :

 Pneumothorax

 Pleural effusion greater than 500 ml estimated from ultrasonography

 Thoracic surgery in the last 3 months

 Contra-indication to CXR

 contra-indication to PEEP of 15 cm H2O

 contra-indication to PEEP of 15 or PEEP 15 mandated

 pressure-volume curve not feasible

 refusal to participate

 language barrier of the next of kin

 child-bearing woman

 person under legal protection

['Acute Respiratory Distress Syndrome (ARDS)']


Epidemiologic Study to Evaluate the Proportion of Cardiovascular Disease Risk Factors in Korean Hypertensive Patients

Summary: The purpose of this study is investigating the proportion of Cardiovascular disease risk factors of hypertensive patients.
Inclusion criteria: inclusion criteria:

 Essential hypertensive patient no less than 18 yeas old

 Patient who gave informed consent form

Exclusion criteria: :

 Patient was diagnosed as secondary hypertension

 Patient who have white-coat hypertension


Immunogenicity and Safety of a Monovalent Glycoprotein-Conjugated (Diptheria Toxin -CRM197) Hib Vaccine in 13-59 Months Old Healthy Children

Summary: This study will evaluate the safety and immunogenicity of single dose of two commercially available vaccines used to prevent Haemophilus influenzae type b infections in children 13-59 months of age.
Inclusion criteria: inclusion criteria:

 Infants 13-59 months of age.

Exclusion criteria: :

 Prior Hib vaccine administration.

 History of serious reaction(s) following vaccination.

 Any vaccination within 7 days of study vaccination.

 Known or suspected immune impairment.

 Premature (before 37th week of gestation) or birth weight less than 2500g

 For additional entry criteria please refer to the protocol.

['Monovalent glyco-conjugated vaccine against Haemophilus influenzae type b (Hib)', 'Tetanus toxoid polysaccharide-conjugated vaccine against Haemophilus influenzae type b (Hib)']

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


Safety and Immunogenicity of Peru-15 Vaccine When Given With Measles Vaccine in Healthy Indian and Bangladeshi Infants

Summary: The purpose of this study is to confirm the safety and immunogenicity of Peru-15 vaccine in infants when given simultaneously with measles vaccine.
Inclusion criteria: inclusion criteria:

 Healthy male and female infants aged 9 - 12 months will be recruited from Vellore, India and Dhaka, Bangladesh.

 All subjects must satisfy the following criteria at study entry:

 Male or female infants aged 9 - 12 months whose parents or primary caretaker have given the written informed consent prior to study entry

 Will comply with the requirements of the protocol (i.e. available for follow-up visits and specimen collection).

 Healthy subjects as determined by:

 Medical history

 Physical examination

 Clinical judgment of the investigator

Exclusion criteria: :

 Parents or primary caregiver are unwilling or unable to give written informed consent to participate in the study

 Ongoing serious chronic disease

 Immunocompromising condition or therapy

 Abdominal pain or cramps, loss of appetite, nausea, general ill-feeling or vomiting in the past 24 hours

 Intake of any anti-diarrheal medicine in the past week

 Acute disease one week prior to enrollment, with or without fever. Temperature ≥38ºC (oral) or axillary temperature ≥ 37.5ºC warrants deferral of the vaccination pending recovery of the subject

 Receipt of antibiotics in the past 2 weeks

 Receipt of live or killed enteric vaccine in the last 4 weeks

 Diarrhea (3 or more loose stools within a 24-hour period) 6 weeks prior to enrollment

 One or two episodes of diarrhea lasting for more than 2 weeks in the past 6 months

 One or two episodes of abdominal pain lasting for more than 2 weeks in the past 6 months

 Receipt of killed oral cholera vaccine

 Have previously received a dose of a measles-containing vaccine (MCV)

 Have previously presented with a disease potentially related to measles

 Receipt of blood, blood products or a parenteral immunoglobulin preparation in the previous 3 months

 History of anaphylaxis, any serious vaccine reaction, allergy to eggs, egg products or to any measles vaccine component

 any condition which in the opinion of the investigator, might interfere with the evaluation of the study objectives

['Cholera', 'Diarrhea', 'Vibrio Infections']


A Dose Escalation Study of Intranasal Neuropeptide Y in Post Traumatic Stress Disorder (PTSD)

Summary: This study is designed to investigate the safety of intranasal administration of NPY using a dose escalation, randomized, double-blinded, placebo-controlled crossover design in a medication-free, symptomatic PTSD group.
Inclusion criteria: inclusion criteria:

 Men and women, age 18-60.

 Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document. We determine whether they have a sufficient understanding of the study procedures and risks by asking them to explain what's involved in the study and to give examples of study risks and benefits.

 Participants must fulfill DSM-IV criteria for current PTSD, based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and on the Clinician-Administered PTSD Scale (CAPS).

 CAPS score must be at least 40 (moderate PTSD severity) at screening.

Exclusion criteria: :

 Current, primary Axis I disorders other than PTSD.

 History or current bipolar disorder or primary psychotic disorders (e.g. schizophrenia, schizoaffective disorder).

 Current diagnosis of anorexia nervosa or bulimia nervosa.

 Women who are pregnant or are breast-feeding.

 Drug or alcohol abuse or dependence within the preceding 3 months.

 poorly controlled hypertension (manifest by SBP > 140 and/or DBP > 90); HR < 60 or > 100 at rest at the time of screening and confirmed immediately prior to randomization

 Evidence of coronary artery disease as evidenced by history, abnormal ECG, typical symptoms

 History of arrhythmia, cardiac surgery, or family history of sudden death

 Hepatic dysfunction as defined by AST and ALT > 2x URL, or alkaline phosphatase and bilirubin > 1.5 x URL within X days prior to randomization

 Chronic renal disease as defined by serum creatinine > 1.9

 Any other serious or unstable clinically significant abnormal findings of laboratory parameters, physical examination, or ECG as determined by the PI.

 Any other serious or unstable condition that would put the subjects at undue risk as determined by the PI or additional safety monitor.

 Serious and imminent suicidal or homicidal risk.

 Psychotropic medication that will not be tapered off at least 7 days prior to screening; withdrawal symptoms must be absent at the time of screening

 History of nasal disorders or sinonasal surgery, or significant nasal abnormalities based on nasal exam.

 Received investigational intervention within 30 days prior to randomization


ReoPro and Retavase to Restore Brain Blood Flow After Stroke

Summary: This study will evaluate the safety and effectiveness of two types of blood thinners, abciximab (ReoPro) and reteplase (Retavase) for restoring normal brain blood flow after ischemic stroke (stroke resulting from a blood clot in the brain).~The only therapy approved by the Food and Drug Administration to treat ischemic stroke is the clot buster drug rt-PA. This treatment, however, is effective only if begun within 3 hours of onset of the stroke and most patients do not get to the hospital early enough to benefit from it. There is thus a pressing need to develop effective stroke treatments that can be initiated more than 3 hours after onset.~Patients between 18 and 80 years of age who have experienced a mild or moderate acute stroke between 3 and 24 hours before starting study drugs may be eligible for this study. Candidates will be screened with a physical examination, blood tests and a magnetic resonance imaging (MRI) scan (if an MRI was not done during the stroke evaluation).~All participants will receive ReoPro. Some will also receive Retavase, which may boost the effectiveness of ReoPro. Retavase is administered in a single dose through a needle in the vein over 2 minutes. ReoPro is infused into the vein over 12 hours. Patients will be monitored with physical examinations, blood tests, computed tomography (CT) scans, and three or four MRI scans of the brain to evaluate both the response to treatment and side effects of the drugs. An MRI scan will be done 24 hours, 5 days and 30 days after starting the study medication, and possibly during screening for this study.~CT involves the use of specialized x-rays to obtain images of the brain. The patient lies still in the scanner for a short time while the X-ray images are formed. MRI uses a strong magnetic field and radio waves to demonstrate structural and chemical changes in tissue. MRI is more sensitive than x-ray in evaluating acute stroke. The patient lies on a table in a metal cylinder (the scanner) while the pictures are being taken. During part of the MRI, a medicine called gadolinium contrast is injected in a vein. This medicine brightens the images, creating better pictures of the blood flow.
Inclusion criteria: inclusion criteria:

 Patients may be enrolled in the study only if they meet all of the following criteria:

 Diagnosis of acute ischemic stroke with onset between 3 and 24 hours prior to planned start of study drugs. Acute ischemic stroke is defined as a measurable neurological deficit of sudden onset, presumed secondary to focal cerebral ischemia, and not otherwise attributable to ICH or another disease process. Stroke onset will be defined as the time the patient was last known to be without the new clinical deficit. Patients whose deficits have worsened in the last 24 hours are not eligible if their first symptoms started more than 24 hours before. If the stroke started during sleep, stroke onset will be recorded as the time the patient was last known to be intact. A careful history is important to determine when the patient was last without the presenting deficits.

 Disabling neurological deficit attributable to the acute stroke at the start of study drugs.

 NIHSS less than or equal to 16.

 Evidence on PWI MRI of a perfusion defect corresponding to the acute stroke syndrome of at least 2cm in diameter in both long and short axis in any slice. The PWI will be assessed by relative mean transit time (MTT) images. The MRI evaluation must involve echo planar diffusion weighted imaging, MRA, and MRI perfusion. A normal appearing MRA with an appropriate perfusion defect is eligible. An apparent stenosis or occlusion on MRA with normal appearing perfusion distally will not be eligible. Poor quality or uninterpretable MRA will not make patient ineligible. Patients who have a normal DWI are eligible.

 Age 18 - 80 years, inclusive.

Exclusion criteria: :

 Patients will be excluded from the study for any of the following reasons:

 General:

 Current participation in another study with an investigational drug or device within, prior participation in the present study, or planned participation in another therapeutic trial, prior to the final assessment in this trial.

 Time interval since stroke onset of less than 24 hours impossible to determine with high degree of confidence.

 Symptoms suggestive of subarachnoid hemorrhage, even if CT or MRI scan is negative for hemorrhage.

 Evidence of acute myocardial infarction defined as having at least two of the following three features: 1.) Chest pain suggestive of cardiac ischemia; 2.) EKG findings of ST elevation of greater than 0.2 mV in 2 contiguous leads, new onset left bundle branch block, ST segment depression, or T-wave inversion; 3.) Elevated troponin I

 Contraindication to MRI scan.

 Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.

 Patients who would refuse blood transfusions if medically indicated.

 Stroke Related:

 Neurological deficit that has led to stupor or coma (NIHSS level of consciousness score greater than or equal to 2).

 High clinical suspicion of septic embolus.

 Minor stroke with non-disabling deficit or rapidly improving neurological symptoms.

 Baseline NIHSS greater than 16.

 MRI/CT Related:

 Evidence of acute or chronic ICH by head CT or MRI.

 Evidence of microbleed on gradient echo MRI (GRE).

 CT or MRI evidence of non-vascular cause for the neurological symptoms.

 Signs of mass effect causing shift of midline structures.

 Incomplete or uninterpretable DWI and PWI.

 DWI abnormality larger than approximately one third of the territory of the middle cerebral artery territory by qualitative assessment.

 Satellite DWI hyperintensity with corresponding hyperintensity on T2 weighted image or FLAIR in a vascular territory different than the index stroke (this is evidence of a new ischemic lesion possibly greater than 24 hours in duration).

 Safety Related:

 Persistent hypertension with systolic BP greater than 185 mmHg or diastolic BP greater than 110 mmHg (mean of 3 consecutive arm cuff readings over 20-30 minutes), not controlled by antihypertensive therapy or requiring nitroprusside for control.

 Anticipated need for major surgery within 72 hours after start of study drugs, e.g., carotid endarterectomy, hip fracture repair.

 Any intracranial surgery, serious head trauma (any head injury that required hospitalization), within the past 3 months.

 Stroke within the past 3 months.

 History of ICH at any time in the past.

 Major trauma at the time of stroke, e.g., hip fracture.

 Blood glucose greater than 200 mg/dl.

 Presence or history of intracranial neoplasm (except small meningiomas) or arteriovenous malformation.

 Intracranial aneurysm, unless surgically treated greater than 3 months.

 Major hemorrhage in past 21 days.

 Major surgery, serious trauma, lumbar puncture, arterial puncture at a non-compressible site, or biopsy of a parenchymal organ in last 14 days. Major surgical procedures include but are not limited to the following: major thoracic or abdominopelvic surgery, neurosurgery, major limb surgery, carotid endarterectomy or other vascular surgery, and organ transplant. For non-listed procedures, the operating surgeon should be consulted to assess the risk.

 Presumed or documented history of vasculitis.

 Known systemic bleeding disorder, e.g., von Willebrand's disease, hemophilia, others.

 Platelet count less than 100,000 cells/microL.

 Congenital or acquired coagulopathy (e.g. secondary to anticoagulants causing either of the following:

 Activated partial thromboplastin time (aPPT) prolongation greater than 2 seconds above the upper limit of normal for local laboratory, except if due to isolated factor XII deficiency. Protamine sulfate reversal of heparin effect does not alleviate this criterion.

 INR greater than or equal to 1.4. Patients receiving warfarin prior to entry are eligible provided INR is less than 1.4 and warfarin can be safely discontinued for at least 48 hours.

 Potentially Interfering with Outcome Assessment:

 Life expectancy less than 3 months.

 Other serious illness, e.g., severe hepatic, cardiac, or renal failure; acute myocardial infarction; or a complex disease that may confound treatment assessment.

 Serum creatinine, AST or ALT greater than 3 times the upper limit of normal for the local laboratory.

 Drug Related:

 Treatment of the qualifying stroke with any thrombolytic or GPIIbIIIa inhibitor outside of this protocol.

 Any administration of a thrombolytic drug in the prior 7 days.

 Treatment of the qualifying stroke with intravenous heparin unless aPTT prolongation is no greater than 2 seconds above the upper limit of normal for local laboratory prior to study drug initiation.

 Treatment of the qualifying stroke with a low molecular weight heparinoid.

 Previous administration of abciximab, if known.

 Known allergy to murine proteins.

 Anticoagulation (evidenced by PT, PTT, or platelet count) caused by herbal therapy.

['Abciximab (ReoPro) and Reteplase (Retavase)']


Assessment of the Effects of Atorvastatin Therapy on Myocardial Deformation Characteristics, in Patients With STEMI

Summary: The primary goal~• To assess the effect of atorvastatin in patients treated since the first 24-96 hours of the disease on the parameters of global and regional myocardial deformation in the infarcted area and the structural and functional properties of arteries at day 7, at 12, 24, 36 and 48 weeks of treatment;~The secondary goals. To evaluate the effect of treatment:~on the parameters of the global and regional myocardial deformation in the intact area on day 7, on 12, 24, 36 and 48 weeks of treatment;~on the parameters of the global and regional myocardial deformation depending on the degree of coronary blood flow restoration by thrombolysis in myocardial infarction (TIMI)~on systolic and diastolic left ventricular function in the presence of initial impairments, or absence of the negative dynamics of these parameters in case of normal baseline values;~on the clinical diagnostic criteria for the development or progression of heart failure;~the dynamics of the duration and extent of myocardial ischemia according to the daily ECG monitoring on day 7, at 12, 24, 36 and 48 weeks of treatment;~the appearance of new prognostically significant cardiac arrhythmias~on the pulse wave velocity~the thickness of the intima-media complex (IMT); 200 patients are planned to be include in a randomized, single-center, open, prospective, controlled clinical trial, the enrollment will be held at the Department of Therapy of Medical Institute of Penza State University.~Definition of the study group:~The patients with STEMI (myocardial infarction with ST-segment elevation) will be included in the study~Group 1 STEMI - 100 patients receiving atorvastatin 80 mg / day for 48 weeks;~Group 2 STEMI - 100 patients receiving atorvastatin 20 mg / day for 48 weeks Planned number of patients: Pre-Screening - 300 subjects; screening and randomization - 200 subjects.~Patients will be randomized by random number generation to include in the group 1 or 2. All included patients will be on the standard basis therapy of the coronary artery disease, according to the national recommendation.
Inclusion criteria: inclusion criteria:

 Signed Informed Consent Form

 Patients having physical and mental ability to participate in the study

 Patients of both sexes aged 35 to 65 years

 Presence of documented ST-elevation myocardial infarction confirmed by ECG, as well as troponin I and CK-MB levels.

 Presence of hemodynamically relevant stenosis of one artery (i.e., the infarct-related artery) confirmed by coronary angiography (CAG), with the occlusion of other arteries not exceeding 30%.

Exclusion criteria: :

 A history of repeat or recurrent myocardial infarction;

 A history of chronic heart failure (CHF) III-IV by New-York Heart Association (NYHA);

 Presence of left ventricular hypertrophy confirmed by echocardiography;

 QRS complex exceeding 1.0;

 Ejection fraction less than 40%;

 Presence of hemodynamically relevant stenosis exceeding 30% in several coronary arteries confirmed by CAG;

 Type 1 diabetes mellitus;

 Type 2 diabetes mellitus requiring pharmacotherapeutic correction with insulin;

 Any severe concurrent disease;

 A history of acute cerebrovascular accident (ACVA) within the 6 month period preceding the study;

 Active hepatic disease or liver enzyme elevation of unclear etiology more than 3 times higher than the upper limit of normal;

 Hepatic failure or bilirubin elevation more than 1.5 times higher than the upper limit of normal;

 Uncontrolled arterial hypertension (AH), with systolic blood pressure (SBP) exceeding 180 mm Hg and diastolic blood pressure (DBP) exceeding 110 mm Hg;

 A history of heart rhythm and/or cardiac conduction disorder;

 Inborn and/or acquired heart defects;

 A history of aortic aneurysm;

 Current existence of severe anemia (Hb < 100 g/L);

 Chronic renal disease (creatinine clearance < 30 mL/min);

 Uncorrected thyroid dysfunction, with hyper- or hypothyroidism;

 Intolerance of statins;

 Alcohol abuse and drug use;

 Participation in other clinical studies within the last two months.


Evaluating a Small Change Approach to Preventing Long Term Weight Gain in Overweight and Obese Adults

Summary: Obesity is a major risk factor for disease and a public health problem. Recent information suggests that while it is possible for most overweight adults to lose a substantial amount of weight, maintaining the weight loss for any extended time (2 to 3 years) is very difficult. This is because trying to maintain big changes in exercise and/or eating behaviour is very difficult in today's environment that makes sustain big changes in behaviour (Example: eat allot less or exercise allot more) very hard. In fact at this time health professionals are unsure of how best to help overweight adults maintain big behavioral changes for long periods of time. In response, we propose that making smaller changes in eating and exercise habits every day may be possible in today's environment and if so, small weight changes may be possible to maintain for long periods of time. This study is designed to assess whether making small changes in eating and exercise behavior will be associated with sustained weight loss over three (3) years. The results of the study may have important implications for development of public health messages and clinical guidelines for prevention and treatment of obesity through small changes in both exercise and eating habits.
Inclusion criteria: inclusion criteria:

 Men and women between 25 and 65 years of age.

 Overweight or Class I or Class II BMI.

 Walk without assistance.

 Commit to a schedule of assessment visits

Exclusion criteria: :

 Physical impairment which would make the intervention very difficult, or unsafe according to the patient's physician including history of myocardial infarction, stroke, coronary bypass surgery or angioplasty in the last 6 months; peripheral artery disease, unstable angina or ischemia.

 Enrolled within past year in a formal weight loss program

 Reported losing greater than 5% of current body weight in the previous 6 months,

 Smoking

 Plans to move from the area,

 Participating in another research study.

 Clinically judged to be unsuitable for participation or adherence as determined by the participants physician

 Inability or unwillingness to provide informed consent.

['Control group', 'Lifestyle counselling']

['Obesity', 'Prevention of Weight Gain']


Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy

Summary: This is a trial to determine whether giving a patient a tailored dose of voriconazole is safe and effective.
Inclusion criteria: inclusion criteria:

 Any adult ≥18 years old

 Patients where a new course of voriconazole is indicated for suspected or confirmed invasive aspergillosis or other serious fungal infections that is deemed by the treating physician to be susceptible to voriconazole

 Patients must have venous access to permit the administration of voriconazole and enable the procurement of multiple plasma samples to measure voriconazole concentrations.

 Estimated creatinine clearance ≥ 50 mL/min

 Able to give written informed consent

 Considered fit to receive the trial treatment

 Able to remain in the hospital for at least 5 days or until they complete their trial treatment

 Female patients must satisfy the investigator that they are not pregnant, or are not of childbearing potential, or are using adequate contraception

 Men must also use adequate contraception

Exclusion criteria: :

 Patients with an estimated creatinine clearance < 50 mL/minute (this precludes the use of intravenous voriconazole)

 Patients receiving any form of renal replacement therapy i.e. haemodialysis or haemofiltration

 Patients with hepatic insufficiency

 Female patients that are pregnant, breast feeding or planning pregnancy during the study

 Past history of intolerance to voriconazole

 Age <18

 Evidence of a clinically relevant fungal isolate that is resistant to voriconazole

 QT prolongation on ECG

 Use of other medications that contraindicate the use of voriconazole

 Patients receiving any other medications that are contraindicated with the use of voriconazole i.e. terfenadine, long acting barbiturates, ergot alkaloids, etc. (Refer to SMPC). Only patients on rifampicin, rifabutin, phenytoin, and carbamazepine would have voriconazole precluded. Voriconazole influences with the pharmacokinetics of many additional agents- (see SMPC)- most importantly anti-rejection compounds- cyclosporine, tacrolimus]

 Uncontrolled cardiac, respiratory or other disease or any serious medical or psychiatric disorder that would preclude trial therapy or informed consent.

 Hypersensitivity to Voriconazole, its excipients or other triazoles

['Immunocompromised Patient', 'Aspergillosis', 'Fusarium']

Immunocompromised Patient
Aspergillosis
Fusarium


Community Acquired Pneumonia: Outcome, Quality of Life and Immune Status

Summary: Community acquired pneumonia (CAP) is an important health problem with significant morbidity, mortality and cost. The most identified pathogen in CAP is Streptococcus pneumoniae. This was also the causative agent most frequently found in the Ovidius and Triple-P study, two consecutive clinical trials initiated by the St. Antonius Hospital Nieuwegein. Diagnosis of pneumococcal pneumonia can be based on positive blood cultures, sputum cultures, urine antigen testing or a serotype specific antibody response. When pneumococcal pneumonia is diagnosed by a positive culture, a matching serotype specific antibody response is expected. However not all patients in the Ovidius and Triple-P study with a culture proven pneumococcal pneumonia showed an antibody response against the infecting pneumococcal serotype. Patients who survived pneumococcal pneumonia are considered as a high-risk population for pneumococcal disease in the future. Possibly these patients have an impaired immune response against S. pneumoniae. In this study, pneumococcal vaccination of patients with S. pneumoniae CAP in the past enables investigating their immune response after vaccination compared to patients with CAP due another causative agent. Furthermore this study provides information to determine if there is a difference in vaccination response between pneumococcal pneumonia patients who had a culture matching serotype specific antibody response and between pneumococcal pneumonia patients who failed to elicit this response previously. Possibly these latter patients had a temporarily low titre due to the infection but another explanation is that there might be a structurally impaired immune response against S. pneumoniae or certain serotypes.
Inclusion criteria: inclusion criteria:

 Patients who participated in the Ovidius or Triple-P study (2004-2009).

 Diagnosis in these studies with pneumococcal pneumonia or pneumonia due another identified organism.

 Age ≥ 18 years.

 Signing of informed consent.

Exclusion criteria: :

 Diagnosis of pneumonia without an identified causative organism.

 Fever at time of vaccination.

 Previous/known allergic reaction to any of the components of the vaccine given.

 Mentally incompetent.

 Previous pneumococcal conjugate vaccination.

 Pneumococcal polysaccharide vaccination within 6 months prior to inclusion.

 Clinical pneumonia within 1 month prior to inclusion.

['Pneumonia', 'Streptococcus Pneumoniae', 'Immune Response']

Pneumonia
Streptococcus Pneumoniae
Immune Response


LDL-Cholesterol Lowering Effect of KB2115 as Add on to Statin

Summary: Thyroid hormones are known to reduce cholesterol levels through regulation of a number of key enzymes involved in synthesis, degradation, and lipid transport. However, the currently marketed thyroid agonists are non-selective, and cannot be used for the treatment of hypercholesterolemia due to extrahepatic consequences of hyperthyroidism, especially on heart, bone, and muscle.~To take advantage of thyroid hormone effect on lipid metabolism for the treatment of hypercholesterolemia, it is necessary to develop a selective thyroid receptor agonist that can induce hyperthyroidism in the liver, while an euthyroid state is preserved in the extrahepatic tissue. KB2115 is a thyroid agonist developed to be liver selective.~The purpose of the study is to assess the efficacy and safety of KB2115 as add on therapy to low and middle doses of statin following 12 weeks of exposure compared to placebo. The aim of the study is to assess efficacy (LDL-cholesterol lowering effects) and safety of KB2115 at doses between 25 and 100 µg and to define a clinically relevant dose or dose range for future studies.
Inclusion criteria: inclusion criteria:

 Signed informed consent

 Males or females aged 18 to 75 years. Female patients must be non-fertile. To be considered as non-fertile, females must fulfil the following:

 Non-nursing and non-pregnant 12 months prior to enrolment

 Not of child bearing potential ie, either documented irreversible surgically sterile (bilateral oophorectomy or hysterectomy is acceptable, but not tubal ligation) or post-menopausal. Post-menopausal is defined as serum follicle-stimulating hormone (FSH) levels in the post-menopausal range combined with amenorrhea for more than 1 year in a woman above 50 years of age, or amenorrhea for more than 2 years below 50 years of age

 Patients with hypercholesterolemia treated with stable doses of the below listed lipid lowering medication for at least 3 months prior to randomization

 Atorvastatin not more than 20 mg/day or

 Simvastatin not more than 40 mg/day

 LDL-cholesterol > 3.0 mmol/L (Week -1)

 Subject able and willing to comply with all study requirements

 At randomization, diet as instructed by the investigator during the last 4 weeks prior to randomization and willingness to follow these instructions throughout the study

Exclusion criteria: :

 Cholesterol lowering agents other than the defined statins

 History of somatic or psychiatric disease/condition, which may interfere with the objectives of the study as judged by the investigator

 Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product as judged by the investigator

 Chronic (> 3 months) pain condition requiring daily medication with pain killers

 Glycosylated haemoglobin (HbA1c) > 7.0%

 Diabetes requiring medication other than metformin

 Clinically abnormal physical findings and laboratory values as judged by the investigator and abnormal resting ECG, eg, QTc interval > 450 msec

 Body Mass Index of ≥ 40 kg/m2

 Resent history (< 3 month) of stroke or transient ischemic attacks

 History of seizure disorder, except febrile convulsions

 A current diagnosis of cancer, unless in remission

 Blood pressure (BP) of > 160/95 mm Hg

 History of cardiac arrhythmia, such as intermittent supraventricular tachyarrhythmia and atrial fibrillation

 Unstable angina pectoris, myocardial infarction or coronary bypass graft surgery or percutaneous coronary intervention < 6 month before randomization

 Congestive heart failure New York Heart Association Class > 2

 Unstable or severe angina pectoris or peripheral artery disease

 Known thyroid disease or thyroid biomarkers (TSH, T3, free T3, T4, free T4) outside reference range for normal at enrolment and at baseline

 Positive urine pregnancy test in women at enrolment

 Use of thyroid replacement therapy and hormone replacement therapy (including contraceptive pills) for last 3 months before randomization


Strength Training in Duchenne Muscular Dystrophy

Summary: Duchenne muscular dystrophy (DMD) is a debilitating neuromuscular disease that causes muscle breakdown, weakness, and eventual death. Over the last 40 years parents have received little guidance on the potential of exercise as a therapeutic strategy to maintain muscle function. It is well known that high intensity exercise and eccentric contractions can result in muscle damage in dystrophic muscle, yet the absence of muscle loading will conversely result in muscle wasting. Recent research in rodent models and milder forms of muscular dystrophy supports earlier studies that resistance exercise may have beneficial effects for maintenance of muscle mass in dystrophic muscle. However, careful and systematic investigation into the safety and feasibility of resistance exercise is needed to consider its implementation in boys with DMD.~The goal of this project is to assess the safety and feasibility of a home based mild to moderate-intensity strengthening exercise program in boys with Duchenne muscular dystrophy (DMD). Evidence from milder forms of muscular dystrophy and mouse models of DMD suggests that strengthening exercise may be beneficial for these children, but this area has not been adequately explored using human subjects. The results of this study should provide information to assist in the development of scientifically based recommendations concerning optimal exercise parameters for patients with DMD.
Inclusion criteria: inclusion criteria:

 Diagnosis of DMD confirmed by

 clinical history with features before the age of five

 physical examination

 elevated serum creatine kinase level

 absence of dystrophin expression, as determined by immunostain or Western blot (<2%) and/or DNA confirmation of dystrophin mutation.

 Age 7 to 10.5 years: a lower age limit of 7 years was selected, since in our experience children younger than 7 years are likely unable to cooperate and comply with all of the exercise measures as needed. An upper age limit of 10.5 years has been set as boys with DMD tend to reach a rapid progression into a late ambulatory phase soon after this age.

 Ambulatory at the time of the first visit, defined as the ability to walk for at least 100 m without an external assistive device and able to climb four stairs.

 Currently using corticosteroids (prednisone or deflazacort) as prescribed by a physician.

Exclusion criteria: :

 Contraindication to an MR examination (e.g. aneurysm clip, severe claustrophobia, magnetic implants)

 Presence of a condition in control subjects or a secondary condition in boys with DMD that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)

 Secondary condition leading to developmental delay or impaired motor control (e.g. cerebral palsy)

 Secondary condition that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)

 Unstable medical condition (e.g. uncontrolled seizure disorder)

 Behavioral problems causing an inability to cooperate during testing

['Aim 2 Exercise group', 'Aim 1 Exercise Dosing', 'Aim 2 Control group']

Aim 2 Exercise group
Aim 1 Exercise Dosing
Aim 2 Control group


The Effect of a Father Inclusive Psychoeducation Program on Postnatal Depression

Summary: Study hypothesis: Childbearing couples who receive the father inclusive psychoeducation program will have: (a) a lower level of depressive symptoms, (b) a higher level of marital relationship, and (c) a higher level of quality of life at 6 weeks, 6 months and one year postpartum than those who receive the usual perinatal care.
Inclusion criteria: inclusion criteria:

 aged 18 or above;

 first-time parents;

 able to speak and read the Chinese language; and

 Hong Kong residents.

Exclusion criteria: :

 couples with past or family psychiatric history


The Laparoscopic Appendicitis Score; a Multicenter Validation Study

Summary: SUMMARY~Rationale: A diagnostic laparoscopy is a frequently used method to confirm the diagnosis appendicitis. However until recently evidence-based laparoscopic criteria for determining appendicitis were not defined. If there is any doubt about the presence of appendicitis the appendix is usually removed. In a single centre prospective pilot study on 134 patients the investigators were able to define the Laparoscopic APPendicitis (LAPP) score. In the current study the investigators will validate the LAPP score in order to decrease the negative appendectomy rate by 50%. Eventually the score should lead to a decrease in morbidity.~Objective: To decrease the negative appendectomy rate by 50%.~Study design: A multicenter prospective validation study~Study population: All patients, ≥18 years, operated with a diagnostic laparoscopy for the clinical suspicion appendicitis. Sample size calculation, performed by a statistician/ epidemiologist of the Trial Coordination Centre, showed the need to analyse 778 patients.~Intervention (if applicable): Patients operated on appendicitis in 2008 and 2009 (n=843), were retrospectively analysed for negative appendectomies. This cohort will serve as the control group. In this control group no intervention was given, as the LAPP score was not yet defined.~In the 778 prospective analysed patients, the LAPP score will be used during a diagnostic laparoscopy. With the LAPP score the investigators intend to halve the number of negative appendectomies.~Main study parameters/endpoints: A decrease in the negative appendectomy rate from 9% to 5%. This decrease should not lead to an increase in missed appendicitis (occurring within 30 days), defined as requiring a surgical re-intervention or as an appendicitis or appendicular infiltrate on an ultrasound or CT-scan.~Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk of implementation of the LAPP score is minimal. In theory, the use of the LAPP score might lead to an increase risk in missed appendicitis. This might lead to an increase in morbidity.
Inclusion criteria: inclusion criteria:

 Patients operated for the clinical suspicion of acute appendicitis that will undergo a diagnostic laparoscopy.

 Age ≥ 18 years.

 Written informed consent

Exclusion criteria: :

 Diagnostic laparoscopy and planned appendectomy for an appendectomy a froid.

 Primarily chosen for an open appendectomy.

 Not able to give informed consent (for example language barrier or legally incapable).

 Refused informed consent.


Severe Post Partum Haemorrhage (PPH): A Randomized Trial on Transversal Intervention in 6 French Perinatal Networks

Summary: Hypothesis A multifaceted intervention program aimed at increasing the responsiveness of care givers, the adequacy of care provided, and the efficacy of organisation of care, in presence of abnormal blood loss in the immediate post partum has more impact on the incidence of severe PPH and on the costs of care than the current methods of dissemination of clinical practice guidelines.~Intervention Intervention group. The intervention includes three components: (1) outreach visits with local presentation of evidence-based clinical practice guidelines for management of PPH, and discussion of their applicability in the context of local organisation; (2) during these educational visits, reminders - check list, PPH emergency case containing appropriate materials - to be used in case of PPH, will be proposed; (3) finally, cases of severe PPH will be reviewed during peer review sessions organized in each participating unit, to help identifying weaknesses in care provided, and needs for improvement.~Control group. The proposed guidelines for management of PPH will be disseminated through the participating perinatal networks; then each unit will be free to implement them at its own convenience.~Randomisation procedure The trial follows a cluster randomised trial design. Randomisation of maternity units will be stratified by region, status (public versus private) and size (annual number of deliveries). The stratified design will guarantee the comparability of the two arms of the trial at baseline.~Outcome measures The primary outcome is the incidence of severe PPH (number of severe PPH to number of deliveries). A severe PPH is defined as a PPH that was associated with one or more of the following: peripartum haemoglobin drop greater than 4g/dl, blood transfusion, arterial embolisation, surgical procedures such as hysterectomy or arterial ligation, transfer of the mother to intensive care unit, maternal death.~Secondary outcomes include the cost of care and the cost/efficacy ratio, and the incidence of adverse effects of uterotonic drugs.
Inclusion criteria: inclusion criteria:

 For maternity units All maternity units belonging to one of the six perinatal networks of the study are eligible.

 For women All women delivering at a gestational age greater than 22 weeks, in one of the participating maternity unit during the study period, will be eligible.

Exclusion criteria: :

 -


COMPAS (Clinical Otitis Media & Pneumonia Study): Pneumonia & Acute Otitis Media (AOM ) Efficacy Study of the Pneumococcal Conjugate Vaccine

Summary: This is a study in a large number of healthy children less than 3 years old to measure the efficacy of GlaxoSmithKline (GSK) Biologicals' 10-valent pneumococcal conjugate candidate vaccine (Synflorix vaccine, or GSK1024850A) to prevent cases of pneumonia (lung infection) likely caused by bacteria (Streptococcus pneumoniae and Haemophilus influenzae) or cases of otitis media (ear infection) in children under 3 years old.
Inclusion criteria: inclusion criteria:

 A male or female between, and including, 6 and 16 weeks of age at the time of the first vaccination. Pre-term born infants can be included in the study starting from 8 weeks of chronological age at the time of first vaccination and up to 16 weeks of chronological age

 Subjects should be living in the area covered by the surveillance system for community acquired pneumonia (CAP), invasive disease and acute otitis media (AOM) •Written informed consent obtained from the parent or guardian of the subject.

 Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study), that would contraindicate the initiation of routine immunizations outside a clinical trial context.

 Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol

Exclusion criteria: :

 Use of any investigational or non-registered drug or planned use during the study period.

 Use or planned use of any investigational or non-registered vaccine other than the study vaccine(s).

 Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type b, hepatitis A and/or Streptococcus. pneumoniae . Locally recommended EPI vaccines to be given at birth are allowed, but should be administered at least one month before the first dose of the study vaccine .Other locally recommended vaccines are always allowed, even if concomitantly administered with the study vaccines. •Previous or planned vaccination with a registered pneumococcal vaccine such as Prevnar is not allowed. If Prevnar immunization needs to be initiated, due to the presence of a high risk disease for pneumococcal infections for which the Prevnar vaccine is made locally available, the subject can not be enrolled in the study and should be referred to the specific Prevnar immunization program.

 History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.

 History of any neurologic disorders or seizures.

 Acute disease at the time of enrolment

 For Colombia: infants with low birth weight ( less than (<) 2.500 grams)

['Pneumococcal conjugate vaccine GSK1024850A', 'Havrix', 'Engerix-B', 'Infanrix hexa', "GSK Biologicals' DTPa-IPV/Hib vaccine"]


Randomized Controlled Trial of Doxycycline to Prevent Acquisition of Mycoplasma Pneumoniae in an Outbreak Setting

Summary: This study was designed to determine whether taking daily doxycycline during an outbreak of Mycoplasma pneumoniae could prevent a person from getting infected and interrupt ongoing disease transmission during an outbreak. Doxycycline is a treatment for Mycoplasma pneumoniae, but it is not certain that the drug could prevent disease if used prophylactically.
Inclusion criteria: inclusion criteria:

 - Working at hospital facility where outbreak of Mycoplasma pneumoniae occured

Exclusion criteria: :

 - Pregnant, on antiseizure medications, allergic to macrolide antibiotics


Clinical Trial of Hyperbaric Oxygen Treatment in Trigeminal Neuralgia Patients

Summary: The purpose of this study is to determine whether the hyperbaric oxygen treatment reduces pain and improve the life quality in trigeminal neuralgia patients.
Inclusion criteria: inclusion criteria:

 Age 18-70

 Primary TN patient (MRI examination support diagnosis)

 Suffering from this pain for at least 3 months

 VAS﹥40mm

 Patient can assess pain intensity correctly

Exclusion criteria: :

 Undergone surgery for TN(including nerve injections) within the last year

 Oral medicine change within the last week

 With other diseases of nervous system

['Hyperbaric oxygen, Mock hyperbaric chamber']

Hyperbaric oxygen
Mock hyperbaric chamber


Phase I Study of Alpha-Melanocyte Stimulating Hormone in Patients With Acute Renal Failure

Summary: OBJECTIVES: I. Determine the maximum tolerated dose and safety of alpha-melanocyte stimulating hormone (alpha-MSH) in patients with acute renal failure.~II. Determine the safety and pharmacokinetics of alpha-MSH in patients at high risk of acute renal failure after renal transplantation.~III. Determine the safety and pharmacokinetics of alpha-MSH in patients with established ischemic acute renal failure.~IV. Determine the effect of alpha-MSH on interleukin-10 pharmacokinetics.
Inclusion criteria: PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 Group 1: Patients on chronic hemodialysis

 Group 2: Patients at high risk of developing acute renal failure (ARF) after cadaveric renal transplantation Received high risk allograft Cadaveric kidneys with greater than 24 hours of cold ischemia time Donor had rising creatinine before organ procurement Donor over 60 years

 Group 3: Patients with ischemic ARF due to hypotension, surgery, or trauma ARF severity index 20-60% Creatinine clearance 12-14 mL/min Rising creatinine of at least 0.5 mg/dL per day for 2 days without evidence of recovery despite standard supportive care No drug or contrast induced renal failure No oliguric renal failure (creatinine clearance 3-4 mL/min) No prior chronic renal failure Baseline creatinine greater than 2.5 mg/dL (males) or 2.0 mg/dL (females) No ARF due to bacterial or fungal sepsis, nephrotoxins, acute tubulointerstitial nephritis, cyclosporine toxicity, bilateral renal vascular disease, or systemic diseases (hepatorenal syndrome, glomerulonephritis, renal vasculitis, etc.)

 --Prior/Concurrent Therapy--

 Group 1: No recent immunosuppressive therapy Group 2 and 3: No prior renal transplantation No prior alpha-MSH Group 3: No prior dialysis for this episode of ARF No anticipated need for dialysis for at least 24 hours At least 12 hours since prior diuretics, mannitol, or dopamine At least 14 days since prior immunosuppressive drugs

 --Patient Characteristics--

 No recent infection No known reaction to Terumo T175 dialyzer Not a prisoner Not pregnant or nursing No allergy to drugs used in study Not mentally impaired Group 3: No severe nonrenal medical condition that would interfere with the study (e.g., terminal cancer)
Exclusion criteria:


Does Azithromycin Cause QT Prolongation in Hospitalized Patients With Severe Community Acquired Pneumonia?

Summary: The macrolide group of antibiotics can cause QT prolongation, and endanger the patient with life threatening arrythmias. QT prolongation caused by Azythromycin, a relatively new macrolide, is extremely rare, and was not reported in clinical trials. Our hypothesis is that patients hospitalized with severe community acquired pneumonia, usually with multiple comorbid conditions will have a higher rate of QT prolongation, compared to the clinical trials published
Inclusion criteria: inclusion criteria:

 Severe community acquired pneumonia

 treated with azithromycin

 age over 18 years

Exclusion criteria: :

 Azithromycin initiated before hospitalization

 technically undecipherable ECG

 Permanent pacemaker


Postoperative Sleep Disturbances After Zolpidem Treatment in Fast-track Hip and Knee Replacement

Summary: Sleep after surgery has been found to be very distrubed immediately after major surgery. This is also seen after fast-track hip and knee replacement with length of stay of less than 3 days. Disturbed sleep has many adverse effects i.e. fatigue, possible hyperalgesia and decline in cognitive abilities.
Inclusion criteria: inclusion criteria:

 Total hip or knee replacement in fast-track setup

 Age 60 years or above

 ASA class 1-3

Exclusion criteria: :

 Anesthesia within the pas 30 days

 Daily use of alcohol > 21 units / week

 Use of anxiolytics or hypnotics within the past 30 days

 Inability to read and understand Danish

 Marked reduction of sight or hearing

 Parkinson's disease or other neurological disaese causing function deficits

 Inability to cooperate to sleep monitoring

 allergy to the drug tested

['Sleep Duration on the First Night After Surgery']


Comparative Effectiveness of Symbicort vs. Advair Among COPD Patients

Summary: This study is intended to evaluate treatment effectiveness of BFC compared to FSC in COPD patients new to ICS/LABA combination therapy.
Inclusion criteria: inclusion criteria:

 Continuous health plan enrollment for 12 months before and after index Rx, at least one prescription for BFC or FSC during intake period, naive to ICS/LABA therapies in year prior to first prescription claim, COPD diagnosis, aged 40 or over at time of first prescription.

Exclusion criteria: :

 ICS/LABA combination during pre-index period, patients with a claim for BFC and FSC on the same day, patients diagnosed with cancer, patients with long-term OCS medication use during pre-index period.


The Influence of Vitamin D on Atypical Antipsychotic-induced Weight Gain

Summary: Schizophrenia and bipolar disorders are major public health problems. The second generation anti-psychotic drugs have efficacy for both positive and negative symptoms and a favorable risk profile as far as movement disorders. However, these drugs are associated with clinically significant weight gain and metabolic effects. The underlying mechanisms of these side effects are unclear, however in our preliminary studies with schizophrenic patients on atypical anti-psychotic drugs, we found that weight gain and vitamin D deficiency was present in about 50% of this population. Given the considerable heterogeneity among the patients on atypical anti-psychotics and potential for weight gain in vitamin D-deficient states, we propose that patients with schizophrenia who gain weight on atypical antipsychotic medications are vitamin D-deficient. This hypothesis will be tested in patients with schizophrenia receiving second-generation anti-psychotic drugs for a minimum duration of 4 months. Specific Aim: We predict that the patients with schizophrenia, who gain weight with antipsychotic treatment, are vitamin D-deficient compared to the patients who do not gain weight. We will examine circulating levels of serum 25(OH)D, mRNA transcripts and protein expression of vitamin D receptor (VDR) and the enzymes, CYP24A and CYP27B, in the white blood cells of the subjects and correlate with BMI and the blood levels of leptin and adiponectin.
Inclusion criteria: inclusion criteria:

 • Men and women with a DSM-IV clinical diagnosis of Schizophrenia, Schizoaffective or Bipolar disorder

 21 to 65 years of age; male and female

 A willingness and ability to provide signed informed consent

 The subject should have been on quetiapine 100 mg or more for more than 12 weeks.

Exclusion criteria: :

 Pregnant women

 Subjects considered at high suicide risk based on the MINI Suicidality Module (> 17 points)

 Unstable general medical condition or serious illness (e.g. death or hospitalization is anticipated within one year), poor kidney function or liver function (defined as laboratory values ≥ three times the upper limit of the normal), and seizure disorders except for childhood seizure disorders

 Concurrent therapy with certain psychotropics is permitted, provided that the medication and dose have been stable for the past 90 days

 Patients on concomitant treatment with clozapine and olanzapine are not permitted.

 Patients on immunosuppressant medications or any orexigenic or anorexigenic drug

 Patients on concomitant treatment with amphetamines and/ or methylphenidate

 History of hypothyroidism or thyroxine therapy

 Patients with a known condition or undergoing therapeutic measures that affects weight, including but not limited to: eating disorder, type I diabetes, hyperthyroidism, thyroxine therapy, Topamax therapy, and infectious diseases, such as HIV, hepatitis B, and hepatitis C

 Active supplementation of vitamin D within the last 3 months

['Schizophrenia', 'Metabolic Syndrome', 'Vitamin D Deficiency']

Schizophrenia
Metabolic Syndrome
Vitamin D Deficiency


Clinical and Economical Interest of Endovascular Cooling in the Management of Cardiac Arrest (ICEREA Study)

Summary: According to international guidelines, mild therapeutic hypothermia is recommended for resuscitated patients after cardiac arrest due to ventricular fibrillation. Whether external or internal cooling is superior in terms of prognosis or security remains unknown. The aim of this study is to evaluate in a randomized trial the clinical and economical interests of the endovascular cooling versus the conventional external cooling for the management of hypothermia after cardiac arrest.
Inclusion criteria: inclusion criteria:

 Age between 18 and 79 years old

 Out-of-hospital cardiac arrest (OH-CA) due to a presumed cardiac etiology

 Delay between OH-CA and return of spontaneous circulation (ROSC) < 60 minutes

 Delay between ROSC and starting cooling < 240 minutes

 Patient not obeying verbal command after ROSC and prior to starting cooling

 Availability of the CoolGard device (ALSIUS product)

Exclusion criteria: :

 Do not reanimate order or terminal disease before inclusion

 Known pregnancy

 Clinical hemorrhagic syndrome or known coagulopathy

 Contra-indication to device usage (such as femoral venous access impossible)

 Hypothermia at admission < 30°C

 Etiology of OH-CA thought to be extra-cardiac (trauma, bleeding or anoxia)

 In hospital cardiac arrest

 Refractory shock (need for extra-corporeal life support)


Dose-Finding Study of CS19 Expressing ETEC Challenge Strains

Summary: This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. If an 80% attack rate (AR) for predefined diarrheal disease is achieved without high output diarrhea, the same inoculum will be given to 5 - 10 more subjects for confirmation of AR. If an 80% AR is not achieved, AR and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with DS26-1 as necessary. If the WS0115A strain causes high output diarrhea, the dose will be adjusted down and further dose characterization continued. An iterative process will be used to select the optimal strain and dose with each step reviewed and approved by the medical monitor.
Inclusion criteria: inclusion criteria:

 Male or female between 18 and 45 years of age, inclusive.

 General good health, without significant medical illness, abnormal physical examination findings or clinical laboratory abnormalities as determined by principal investigator (PI) or PI in consultation with the medical monitor and Sponsor.

 Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written examination (pass grade ≥ 70%)

 Willing to participate after informed consent obtained.

 Available for entire inpatient portion of study and all outpatient study visits.

 Negative serum pregnancy test at screening (initial visit and day -7 to - 3) and a negative urine pregnancy test on the day of admission to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Alternatively, abstinence alone is acceptable. Female subjects who are unable to bear children must provide supporting documentation (e.g., prior tubal ligation or hysterectomy).

Exclusion criteria: :

 Presence of a significant medical condition, (e.g., psychiatric conditions or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.

 Immunosuppressive illness or IgA deficiency (below the normal limits)

 Positive serology results for HIV, HBsAg, or HCV antibodies.

 Significant abnormalities in screening laboratory hematology, serum chemistry, urinalysis, as determined by PI or PI in consultation with the medical monitor and Sponsor.

 Allergy to fluoroquinolones, cotrimoxazole, or ampicillin/penicillin (excluded if allergic to two of three).

 Fewer than 3 stools per week or more than 3 stools per day as the usual frequency; loose or liquid stools other than on an occasional basis.

 History of diarrhea in the 2 weeks prior to planned inpatient phase.

 Regular use of laxatives or any agent that increases gastric pH (regular defined as at least weekly).

 Use of antibiotics during the 7 days before bacterial dosing or proton pump inhibitors, H2 blockers, or antacids within 48 hours of dosing.

 Travel to countries where ETEC or cholera infection is endemic (most of the developing world) within two years prior to dosing.

 History of vaccination for or ingestion of ETEC, cholera, or LT toxin.

 Stool culture (collected no more than 1 week prior to admission) positive for ETEC or other bacterial enteric pathogens (Salmonella, Shigella and Campylobacter).

 Use of any investigational product within 30 days preceding the receipt of the challenge inoculum, or planned use during the active study period.

 Use of any medication known to affect the immune function (e.g., corticosteroids) within 30 days preceding receipt of the challenge inoculum or planned use during the active study period. (Topical and intra-articular steroids will not exclude subjects). MANAGEMENT


Lanreotide Autogel in the Treatment of Symptomatic Polycystic Liver Disease

Summary: An open-label, Phase II clinical study to evaluate the efficacy and safety of lanreotide autogel 90mg every 4 weeks in the treatment of symptomatic polycystic liver disease, including a dose escalation at month 6 to lanreotide autogel 120mg for non responders.
Inclusion criteria: inclusion criteria:

 Liver volume ≥ 4 liter

 ≥ 20 liver cysts

 Symptomatic patients defined as at least 2 out of 5 of the following symptoms related to mass effect irrespective of the intensity:

 Abdominal distention perceived as uncomfortable

 Frequent abdominal pain

 Early satiety

 Nausea (with the inclusion of dyspeptic complaints)

 Dyspnea

 Diagnosed with ADPKD or ADPLD

 Male and female patients of 18 years and older

 Written informed consent

Exclusion criteria: :

 Creatinine clearance < 20 ml/min

 Patient who underwent a kidney transplant and received variable doses of immunosuppressive therapy and/or present signs of rejection in the past year

 Hormonal replacement therapy

 Hormonal contraception

 Pregnant or lactating

 Presenting with an uncontrolled disease (other than ADPKD/ADPLD)

 Planned to undergo any surgery of the liver during study participation

 Planned to undergo any surgery of the KIDNEY during study participation (ADPKD patients only)

 Patients with known allergies to somatostatin or its analogues or any of its components

 Patients who received somatostatin analogues in the 6 months preceding study inclusion


Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease

Summary: Main purpose of the study:~To comparatively assess the diagnostic performance of non invasive anatomical and functional imaging modalities to detect significant obstructive coronary artery disease as demonstrated at invasive coronary angiography and functional evaluation of coronary lesions (fractional flow reserve).
Inclusion criteria: inclusion criteria:

 Patients with intermediate (>20%, <90%) risk of IHD based on age,gender,symptoms and exercise stress test results

Exclusion criteria: :

 Age < 30 Yrs or > 75 yrs

 Pregnancy (suspected or ascertained)

 LV Dysfunction (LVEF < 35% by Echo or other method)

 Low (< =20%) or high (>=90%) probability of CAD

 Acute Coronary Syndrome

 Prolonged (> 20 minutes) chest pain

 De novo or accelerated angina

 Hemodynamic or electrical instability

 Recent ST-T segment or T wave changes of ischemic nature

 Acute myocardial infarction with or without ST segment elevation

 Elevated serum cardiac markers of necrosis

 Known diagnosis of CAD

 Previously known myocardial infarction

 Previous PCI

 Previous CABG

 Persistent atrial fibrillation or advanced AV Block

 Asthma or chronic treatment with aminophylline

 Recent (<6 months) cerebral ischemic attack

 Known significant carotid stenosis or vascular aneurisms

 Asthma or chronic treatment with aminophylline

 Active cancer

 Severe hypertension. Patients cannot withdraw therapy for 12 hours.

 Congenital heart disease

 Significant valvular disease

 Cardiomyopathy (e.g. DCM, HCM, ARVC, Amyloidosis)

 Inability to provide an informed consent