Topiramate vs. Placebo in Preventing Weight Gain in Bipolar Disorder Treated With Olanzapine

Summary: The primary objective of this study is to examine the efficacy of topiramate in combination with olanzapine for the prevention of weight gain in youth with bipolar disorder. The secondary objective is to examine the tolerability of topiramate in combination with olanzapine for the prevention of weight gain in youth with bipolar disorder.
Inclusion criteria: inclusion criteria:

 Male or female patients, ages 10-18 years.

 Female patients of menarche must be using a medically accepted means of contraception (e.g. oral contraceptives, Depo-Provera, abstinence).

 Each patient's authorized legal guardian must understand the nature of the study and must provide written informed consent. Each patient must also give assent to study participation.

 Patients must have a diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) bipolar disorder, type I and currently display an acute manic or mixed episode as determined by K-SADS (Geller et al 2000).

 Patients must have a baseline (day 0) Young Mania Rating Scale score of at least 16.

 Subjects should be fluent in English.

Exclusion criteria: :

 Female patients who are either pregnant or lactating.

 Clinically significant or unstable hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical conditions.

 Any history of current or past diabetes that has been treated with pharmacological intervention.

 Neurological disorders including epilepsy, stroke, or severe head trauma.

 Clinically significant laboratory abnormalities (> 3 times upper limit of normal), on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, lipid profile, fasting glucose, urinalysis, or thyroid indices. Clinically abnormal ECG.

 Manic or mixed episode due to a general medical condition or substance-induced mania (DSM-IV-TR).

 Mental retardation (IQ <70).

 History of hypersensitivity to or intolerance of olanzapine or topiramate.

 Prior history of olanzapine or topiramate non-response or allergic reaction.

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

 Judged clinically to be at suicidal risk (defined as having active suicidal ideation, intent or plan, or a serious suicide attempt within 30 days, or a baseline Children's Depression Rating Scale suicide score of >3).

 Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections and day 0.

 Treatment with concurrent mood stabilizers or anticonvulsants, benzodiazepines (except as described below), psychostimulants, guanethidine, or guanadrel, or antidepressants.

 Schizophrenia or other psychotic disorders (including schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified) as defined in the DSM-IV.

 Major depressive disorder, dysthymic disorder, depressive disorder not otherwise specified.


The Effect of Caphosol® on the Development of Esophagitis in (N)SCLC Patients Treated With Concurrent Chemo/Radiotherapy

Summary: Rationale: In the Netherlands 1770 people are being diagnosed with SCLC (Small Cell Lung Cancer) and 8764 patients are being diagnosed with NSCLC (Non Small Cell Lung Cancer) in 2011. This is approximately 15% and 75% of all new diagnosed lungcancers. Part of them will need a combination of chemo-radiationtherapy. A review of the incidence and severity of esophagitis in (N)SCLC patients receiving a combination of chemotherapy and once daily radiotherapy revealed overall esophagitis rates up to 58% experiencing esophagitis grade 2 and higher. As concurrent radiotherapy is moving to twice daily radiation (30 x 1,5 Gy in 3 weeks or 30-35 x 2 Gy in 3 weeks) it is expected that the incidence of esophagitis will rise, the clinical symptoms are likely to arise earlier and become more severe.~Mucositis of the upper tractus digestivus is a serious adverse event leading to pain, problems with swallowing and decreased food intake. It has a negative infect on QoL and can lead to prolonged hospital stay and delayed cancer treatment. Physicians seek improvements in treatment modalities to improve these daily patient toxicities.~Caphosol® is an advanced electrolyte solution indicated as an adjunct to standard oral care in treating oral mucositis caused by radiation or high dose chemotherapy. Positive effects of Caphosol® oral rinse 4 times daily in a study with head and neck chemoradiation patients were found on the presence of mucositis and on oral comfort.~It's supposed that the pathogenesis of chemo- or radiotherapy induced mucositis is the same for the whole tractus digestivus. The appearance does differ due to differences in cell proliferation.~Swallowing Caphosol® after oral rinse could have a positive effect on esophageal mucositis on time of onset, severity and duration.~Objective: Adding the use of Caphosol® (rinsing and swallowing four times a day) to the standard of care for esophagitis/mucositis, reduces the incidence, onset, duration and severity of esophagitis in (N)SCLC patients, comparing to the standard of care alone.~Study design: A multi-centre, open, randomized prospective phase II study. Study population: 108 patients 18 years or older with histologically proven (N)SCLC (all histological subtypes), treated with concurrent chemo- and radiotherapy are estimated to be included in this study (2:1 ratio inclusion; 72 patients with Caphosol® and 36 patients without Caphosol®; α=0.05, power 80%).~Intervention (if applicable): 108 patients eligible for this study will be monitored during their (N)SCLC chemo/radiotherapy treatment. One group of 72 patients will receive Caphosol®, 4 times a day - next to the standard of care. Caphosol® will start at day 1 of treatment and will be continued until 3 weeks after the last radiotherapy (RT).Another group of 36 patients will receive only the current standard of care for esophagitis. The patients will be randomly assigned to one of the groups.~Main study parameters/endpoints: The primary objective is to estimate the incidence, onset, duration and severity of esophagitis in (N)SCLC patients undergoing radiation therapy with chemotherapy who receive Caphosol®.~Secondary study parameters/outcome of the study (if applicable):~To correlate components of esophagitis data with clinical outcomes (pain, dysphagia, analgetic use, oral intake, weight loss, infection, need for hospitalization, QoL)~Discontinuation or delay of chemotherapy due to esophagitis. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risks are very small. The patient has to fill in a Esophagitis Daily Questionnaire and during regular visits QOL questionaires are performed.~Sputumswabs are collected on a weekly basis for determination of the microbiological flora of the mouth. During regular blood control max. 8 ml extra blood is taken for immunologic status research.~Caphosol® is a saturated calciumphosphate solution. The daily intake of calcium and phosphor when swallowing Caphosol® 4 times daily is far beyond the Acceptable Daily Intake (ADI)(< 5%). Compared to daily nutrients like milk (270 mg calcium per unit milk (225 ml)) or meat (200 mg phosphor per 100 g meat) the intake of calcium and phosphor due to Caphosol® is negligible and is considered safe.
Inclusion criteria: inclusion criteria:

 18 years or older

 Patients with histologically proven (N)SCLC (all histological subtypes), treated with concurrent chemo- and radiotherapy.

 Ability to understand the protocol and willing to provide written informed consent

Exclusion criteria: :

 Concurrent participation in a clinical trial in which the subject is taking or receiving any investigational agent that may affect the frequency, severity or duration of mucositis.

 Pre-existent esophagitis.

 Receiving investigational treatment for the prevention or treatment of mucositis.

 Prior irradiation to the lung or head and neck region.

['Small Cell Lung Cancer', 'Non Small Cell Lung Cancer']

Small Cell Lung Cancer
Non Small Cell Lung Cancer


Effectiveness and Safety of Minoxidil Foam Versus Placebo Foam for Androgenetic Alopecia

Summary: The current study aims to show efficacy of twice daily application of 5% Minoxidil Topical Foam (MTF) formulation compared to placebo in the temple region of male patients with androgenetic alopecia after 24 weeks as well as to gain long-term data on the efficacy and safety of 5% MTF in male subjects with AGA in temple and vertex region, over a period of 2 years. Objective and subjective efficacy measures will be compared to baseline. Moreover, all patients will get the equal treatment and measurements in the vertex region to enable comparison of the efficacy of 5% Minoxidil Topical Foam in the temples not only to baseline but also to vertex region. Additionally safety assessments will be performed throughout the whole study.
Inclusion criteria: inclusion criteria:

 Male, age 18 to 70 year old, in general good health

 Exhibits male AGA based on a discernable hair loss in temple and vertex region rating Hamilton-Norwood Scale III vertex to VI (See Appendix 1)

 Subjects who give their consent to the study after thorough explanation and who personally signed and dated the informed consent document indicating that the subject, has been informed of all pertinent aspects of the trial

 Willing to maintain the same hairstyle, hair length and hair color throughout the study

 Subjects who are willing and able to comply with scheduled visits, treatment plan, mini-tattoo and other trial procedures

 Accepting the Information form plus accepting and signing the Informed Consent form

Exclusion criteria: :

 Known to be hypersensitive to minoxidil, hair dye (p-phenylenediamine), tattoo ink, fragrances, hair gel or any vehicle components

 Current or 4 weeks dated back use of medical shampoos or solutions which include Ketoconazole or the like (e. g. Terzolin®) in the target region interfering with the CTM or examination method

 Current or 3 months dated back use of topical treatment in the target regions taken for more then 2 consecutive weeks interfering with the CTM (topical corticosteroids, aminexil, minoxidil, estrogens)

 Current or 3 months dated back use of systemic treatment (drugs or dietary supplement) taken for more than 2 consecutive weeks interfering with the CTM or examination method (beta blocker, cimetidine, diazoxide, isotretionin, corticosteroids, vitamin A intake above 10000 IU per day)

 Current or 12 months dated back use of Finasteride (Propecia®, FinaHair®, etc.), Dutasteride or a similar product

 Within past 12 months undergoing chemotherapy or receiving cytotoxic agents as well as radiation and/or laser/surgical therapy of the scalp

 Current or prior enrollment in any other investigational medication (drug) study within the 4 weeks prior to study initiation

 Presence of hair transplants, hair weaves or non-breathable wigs and hair bonding

 Current or 2 months dated back severe diet or presenting a history of eating disorder

 Any dermatological disorders of the scalp in the target region with the possibility of interfering with the CTM or examination method, such as fungal or bacterial infections, seborrheic dermatitis, psoriasis, eczema, folliculitis, scars or scalp atrophy

 Untreated persisting hypertension

 Active hair loss or history within the past 3 months including diffuse telogen effluvium, alopecia areata, scarring alopecia

 Other severe, acute or chronic medical condition that may lead to hair loss or interfere with the interpretation of trial results (e. g. untreated hypothyroidism)

 Individuals who are institutionalized by court or regulatory order

['Minoxidil', 'vehicle of 5% Minoxidil topical foam']

Minoxidil
vehicle of 5% Minoxidil topical foam


A Clinical Evaluation of Absorb™ Bioresorbable Vascular Scaffold (Absorb™ BVS) System in Chinese Population ~ ABSORB CHINA Randomized Controlled Trial (RCT)

Summary: To evaluate the safety and efficacy of the Absorb BVS System compared to the XIENCE V Everolimus Eluting Coronary Stent System (EECSS) in the treatment of subjects with ischemic heart disease caused by up to two de novo native coronary artery lesions in separate epicardial vessels.
Inclusion criteria: inclusion criteria:

 Subject must be at least 18 years of age at the time of signing the informed consent form.

 Subject or a legally authorized representative must provide written Informed Consent prior to any study related procedure.

 Subject must have evidence of myocardial ischemia (e.g., stable angina, unstable angina, post-infarct angina or silent ischemia) suitable for elective percutaneous coronary intervention (PCI). Subjects with stable angina or silent ischemia and < 70% diameter stenosis must have objective sign of ischemia as determined by one of the following, echocardiogram, nuclear scan, ambulatory ECG or stress ECG. In the absence of noninvasive ischemia, fractional flow reserve (FFR) must be done and indicative of ischemia.

 Subject must be an acceptable candidate for coronary artery bypass graft (CABG) surgery.

 Female subject of childbearing potential does not plan pregnancy for up to 1 year following the index procedure. For a female subject of childbearing potential, a pregnancy test must be performed with negative results known within 14 days (≤14 days) prior to the index procedure per site standard test.

 Female subject is not breast-feeding at the time of the screening visit and will not be breast-feeding for up to 1 year following the index procedure.

 Subject agrees to not participate in any other investigational clinical studies for a period of 1 year following the index procedure.

Exclusion criteria: :

 Any surgery requiring general anesthesia or discontinuation of aspirin and/or P2Y12 inhibitor is planned within 12 months after the index procedure.

 Subject has a known hypersensitivity or contraindication to device material (cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers) and its degradants (everolimus, poly (L-lactide), poly (DL-lactide), lactide, lactic acid). Subject has a known contrast sensitivity that cannot be adequately pre-medicated.

 Subject has a known allergic reaction, hypersensitivity or contraindication to:

 Aspirin; or

 All P2Y12 inhibitors (including clopidogrel and ticlopidine, and prasugrel and ticagrelor when they become available); or

 Heparin and bivalirudin.

 Subject had an acute myocardial infarction (AMI) within 7 days of the index procedure and both creatine kinase (CK) and creatine kinase myocardial-band isoenzyme (CK-MB) have not returned to within normal limits at the time of index procedure.

 Subject is currently experiencing clinical symptoms consistent with new onset AMI, such as nitrate-unresponsive prolonged chest pain with ischemic ECG changes.

 Subject has a cardiac arrhythmia as identified at the time of screening which at least one of the following criteria is met:

 Subject requires coumadin or any other agent for chronic oral anticoagulation.

 Subject likely to become hemodynamically unstable due to their arrhythmia.

 Subject has poor survival prognosis due to their arrhythmia.

 Subject has a known left ventricular ejection fraction (LVEF) < 30% assessed by any quantitative method. LVEF may be obtained within 6 months prior to the procedure for subjects with stable coronary artery disease (CAD). For subjects presenting with acute coronary syndrome (ACS), LVEF must be assessed during the index hospitalization (which may include during the index procedure by contrast left ventriculography) but prior to randomization in order to confirm the subject's eligibility.

 Subject has received CABG at any time in the past.

 Subject has undergone prior PCI within the target vessel during the last 12 months or undergone prior PCI within the non-target vessel within 30 days before the index procedure.

 Subject requires future staged PCI either in target or non-target vessels.

 Subject has received any solid organ transplants or is on a waiting list for any solid organ transplants.

 At the time of screening, the subject has a malignancy that is not in remission.

 Subject is receiving immunosuppressant therapy or has known immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.). Note: corticosteroids are not included as immunosuppressant therapy.

 Subject has previously received or is scheduled to receive radiotherapy to coronary artery (vascular brachytherapy), or chest/mediastinum.

 Subject is receiving or will receive chronic anticoagulation therapy (e.g., coumadin or any other anticoagulation agents).

 Subject has a platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3.

 Subject has a known or documented hepatic disorder as defined as cirrhosis or Child-Pugh ≥ Class B.

 Subject has known renal insufficiency as defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 or dialysis at the time of screening.

 Subject is high risk of bleeding; has a history of bleeding diathesis or coagulopathy; has had a significant gastro-intestinal or significant urinary bleed within the past six months; will refuse blood transfusions.

 Subject has had a cerebrovascular accident or transient ischemic neurological attack (TIA) within the past six months or any prior intracranial bleed, any permanent neurologic defect, or any known intracranial pathology (e.g., aneurysm, arteriovenous malformation, etc.).

 Subject has extensive peripheral vascular disease that precludes safe 6 French sheath insertion. Note: femoral arterial disease does not exclude the subject if radial or brachial access can be used.

 Subject has life expectancy < 2 years for any non-cardiac cause or cardiac cause.

 Subject is in the opinion of the Investigator or designee, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.

 Subject is currently participating in another clinical trial that has not yet completed its primary endpoint or protocol-required medications or invasive procedures.

 Angiographic inclusion criteria

 Assessment of angiographic eligibility is per visual assessment by an investigator both for qualitative and quantitative variables. On-line QCA is recommended to be used for appropriately sizing of the vessel. If on-line QCA cannot be used, visual estimation is required.

 One or two de novo target lesions:

 If there is one target lesion, a second non-target lesion may be treated but the non-target lesion must be present in a different epicardial vessel, and must be treated first with a successful, uncomplicated result prior to randomization of the target lesion.

 If two target lesions are present, they must be present in different epicardial vessels and both satisfy the angiographic eligibility criteria.

 The definition of epicardial vessels means the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA) and their branches. Thus, for example, the subject must not have lesions requiring treatment in both the LAD and a diagonal branch.

 Target lesion must be located in a native coronary artery with a visually estimated or quantitatively assessed %DS of ≥ 50% and < 100% with a thrombolysis in myocardial infarction (TIMI) flow of ≥ 1 and one of the following: stenosis ≥ 70%, an abnormal functional test (e.g., fractional flow reserve, stress test), unstable angina or post-infarct angina.

 Target lesion must have a Dmax (by on-line QCA) or reference vessel diameter (RVD) (by visual estimation) ≥ 2.50 mm and ≤ 3.75 mm (on-line QCA assessment is recommended).

 Target lesion must have a lesion length ≤ 24 mm based on either visual estimation or on-line QCA.

 Angiographic

['Coronary Artery Disease', 'Coronary Artery Stenosis', 'Coronary Disease', 'Coronary Stenosis']

Coronary Artery Disease
Coronary Artery Stenosis
Coronary Disease
Coronary Stenosis


Use of Implanted Microstimulators for Decreasing Spasticity and Improving Motion Following Spinal Cord Injury

Summary: The primary aims of this study are to determine the safety of the RFM System (Alfred Mann Foundation, Santa Clarita, CA) in a patient with incomplete SCI and the effect of the RFM system on lower limb strength and spasticity. The secondary aim is to analyze any improvement in the participant's mobility.
Inclusion criteria: inclusion criteria:

 an incomplete C6 ASIA C (Central Cord) spinal cord injury

 lower motor function impaired and suffers from significant spasticity (Ashworth scale 4)

 able to ambulate approximately 10-20 feet with a rolling walker and minimal assistance

 has sufficient endurance to complete at least two 20-minute therapy sessions per day

 cognitive abilities are intact

Exclusion criteria: :

 psychiatric diagnosis

 medical contraindications

 history of bleeding disorders

 allergy to anesthesia

 acute or progressive disease

 active implantable device

['Spinal Cord Injury at C5-C7 Level With Incomplete Lesion']


Fecal Microbiota Therapy for Recurrent Clostridium Difficile Colitis

Summary: This study was developed in response to the July, 2013 FDA draft guidance regarding FMT for CDI. The weight of the evidence in the literature suggests that FMT is the most effective treatment for ambulatory outpatients affected by recurrent CDI who fail conventional therapy.~The anticipated benefits to research patients enrolled in this study include resolution of chronic diarrhea, return of bowel habits and nutritional status to normal, and resolution of chronic recurrent CDI.~FMT involves the endoscopic instillation of freshly obtained stool with millions of live bacteria into the recipient's colon by endoscopic lavage. With any endoscopic procedure, there is a risk of perforated viscous. This is very rare, but the risk is increased with severe CDI. The risk of acquisition of communicable enteric or blood borne pathogen appears to be negligible.
Inclusion criteria: inclusion criteria:

 Patients > 18 years of age

 The patient has been treated with appropriate antimicrobial therapy for CDI.

 The patient has documented relapse/recurrence of infection as demonstrated by positive stool culture, or cytotoxin assay, or PCR toxin assay.

 Since this study does not involve treatments that have potential teratogenicity, and in general avoidance of antimicrobial treatment during pregnancy is advised (metronidazole is pregnancy category C), women of child-bearing age may be included in the study.

Exclusion criteria: :

 - Patients will be excluded from study participation if one of the following categories of


Evaluation of Levemir® for the Treatment of Type 1 and 2 Diabetes

Summary: This study is conducted in Europe. The aim of this observational study is to evaluate the incidence of serious adverse drug reactions while using Levemir® under normal clinical practice conditions.
Inclusion criteria: inclusion criteria:

 Type 1 diabetes

 Type 2 diabetes

 Candidates of use of a basal insulin as part of their diabetes regimen

Exclusion criteria: :

 Unwilling to adhere to therapy or follow up

 Pregnancy

['Diabetes', 'Diabetes Mellitus, Type 1', 'Diabetes Mellitus, Type 2']

Diabetes
Diabetes Mellitus
Type 1
Diabetes Mellitus
Type 2


Adolescent Vaccination in the Medical Home: Established and Innovative Strategies

Summary: In this project, the investigators will develop, implement, and evaluate an adolescent vaccination quality improvement program, with the program designed to encourage adolescents to visit their usual primary care provider to receive vaccinations and other recommended preventive health services. This study will be conducted in different types of primary care settings, such as public, private, and managed care clinics serving adolescent patients of diverse backgrounds, and will provide important information to help guide future public health efforts to achieve high rates of immunization in adolescents.
Inclusion criteria: inclusion criteria:

 Age 11-17 years old

 Active patient (visit in last 2 years) of clinics in study

 Need one or more vaccines or well-care visit

Exclusion criteria: :

 Up to date on vaccines and well-care

['Text Message Reminder/Recall', 'Parent Preference']

Text Message Reminder/Recall
Parent Preference

:

 Up to date on vaccines and well-care


Objective Diagnostic Markers and Personalized Intervention in MDD Patients

Summary: Major depressive disorder (MDD) is one of the most common psychiatric disorders, with high recurrence rate, suicide rate and disability rate. It's reported that the global burden caused by MDD will be up to the second rank among all the disease burdens by 2020. China is also confronted with the daunting challenges against MDD. It's assessed that the monthly incidence of MDD is 6.1%, non-hospitalizing rate reaches up to 92% and the non-treatment rate is approximate 95%. However, to date, the pathogenesis of MDD is obscure and the current therapies don't work well. Therefore, it's urgent and critical to elucidate the pathogenesis of MDD, to develop early diagnostic criteria and effective intervention in MDD. Considering the diversity of weights on genetic factor and environmental factor in MDD, in this project, the investigators aim firstly to explore the effect of genetic-environmental interactionon the pathogeny of MDD for classifying MDD into genetic type, environmental type and others based on a case-control study. We next conduct the neurobiological, neurocognitive and psycho-behavioral assessments among MDD, schizophrenia and healthy groups to screen the salient endophenotypes for establishing the diagnostic models of MDD . The investigators further analyse the changes of these indicators after 8 weeks'medication to select the potential predictors for therapeutic evaluations and interventional options in MDD patients. Finally, the investigators continue a 2-year follow-up study to test and verify the predictors of prognosis in MDD patients.
Inclusion criteria: For MDD group:

 inclusion criteria:

 Age between 18-55, male or female;

 The diagnosis of MDD consistent with DSM-IV (M.I.N.I)

 First-episode or relapsed;

 Certain ability of reading and writing to complete the questionnaire survey and psychological assessment.

 All participants provide written confirmation of informed consent prior to engaging the study protocol.

Exclusion criteria: :

 Current psychopathology or a history of neurologic conditions, including alcohol/substances dependence, the diagnosis of cognition impairment;

 Severe somatic diseases, such as severe cardio-cerebral vascular diseases, respiratory diseases, liver diseases, kidney diseases, or malignant tumors;

 Not signed the informed consent;

 Been engaging other studies.

 For Healthy control group

 inclusion criteria:

 age between 18 and 55 years at the time of enrollment;

 providing written confirmation of informed consent prior to engaging the study.


Study of SilverHawk®/TurboHawk® in Lower Extremity Vessels (DEFINITIVE™ LE)

Summary: The purpose of the study is to evaluate the intermediate and long-term effectiveness of stand-alone atherectomy treatment of peripheral arterial disease in the legs.
Inclusion criteria: inclusion criteria

 Has a Rutherford Clinical Category Score of 1 - 6.

 Has evidence of ≥ 50% stenosis or occlusion in the superficial femoral, popliteal, anterior tibial, posterior tibial and/or peroneal arteries, confirmed by angiography.

 Has identifiable distal target vessel which upon completion of the intervention, is anticipated to provide re-constitution of blood flow to the foot.

 Exchangeable guidewire must cross lesion(s), with ability of catheter to cross lesion.

 Each discrete target lesion's length is ≤ 20 cm.

 Reference vessel diameter is ≥ 1.5 mm and ≤ 7 mm.

Exclusion criteria:

 Has surgical or endovascular procedure of the target vessel within 14 days prior to the index procedure.

 Has any planned surgical intervention or endovascular procedure within 30 days after the index procedure.

 Has had a previous peripheral bypass affecting the target limb.

 Has end-stage renal disease defined as undergoing hemodialysis for kidney failure.

 Has presence of severe calcification in target lesion(s).

 Has in-stent restenosis of the target lesion.

 Has an aneurysmal target vessel.

 Has significant stenosis or occlusion of inflow tract that has not been revascularized prior to treatment of the target vessel.

 Has perforation, dissection or other injury of the access or target vessel requiring additional stenting or surgical intervention prior to enrollment.

 Has disease that precludes safe advancement of the SilverHawk/TurboHawk device to the target lesion(s).

 Has had a previous amputation above the metatarsal line on the target limb.

['SilverHawk & TurboHawk Peripheral Plaque Excision System']

['Peripheral Arterial Disease', 'Claudication', 'Critical Limb Ischemia']

Peripheral Arterial Disease
Claudication
Critical Limb Ischemia


Guidance for Elderly With Cognitive Disorders

Summary: The purpose of the programme is to facilitate the anticipation of dementia both in elderly patients suffering from this disease and in their carers and to diminish care burden in order to improve quality of life and daily functioning.
Inclusion criteria: inclusion criteria:

 elderly (> 70 years) with mild dementia in presence of a carer.
Exclusion criteria:


Trial of Atorvastatin on the Persistent Coronary Aneurysm in Children With Kawasaki Disease

Summary: Background Kawasaki disease (KD) is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Incidence of late coronary artery aneurysms or ectasia, which may lead to myocardial infarction (MI), sudden death, or ischemic heart disease, decreased after the introduction of intravenous immunoglobulin therapy. However, significant persistent coronary arterial lesions or aneurysms may still occur in about 1-3 % of the patients.~Atorvastatin (Lipitor®), a kind of statin, is a selective competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This drug had been safely and widely used for treatment of adult hyperlipidemia, prevention of coronary heart disease and familial hypercholesterolemia in childhood. In addition to the cholesterol-lowering effects, statins exerts diverse cellular, cholesterol-independent effects, including improvement in endothelial function, inhibition of neurohormonal activation, and reduction in levels of proinflammatory cytokines. Based on the above concepts, some patients with infrarenal abdominal aortic aneurysms received statin therapies and then the growth rate of aneurysms slowed down.~Therefore, the investigators may hypothesize that Atorvastatin is helpful in the regression of persistent coronary lesions in KD patients due to its effect of anti-inflammation. In NTUH, there are about 20 KD patients with coronary lesions persistent for many years. And the investigators plan to conduct the clinical trial with atorvastatin to evaluate the effects of Atorvastatin on the persistent coronary arterial lesions/aneurysms in children with Kawasaki disease including safety and efficacy.~Methods~There are around 20 KD patients eligible for this study. After they sign the IRB-approved ICF, they will be enrolled for this study. Briefly, this study is divided into three stages: screening & enrollment stage (I), treatment & follow-up stage (II) for 1 year and final data analysis stage (III). Measurements include basic vital sign, electrocardiography, liver function, muscle enzyme, inflammatory markers and echocardiography.~Predicted results~1.Oral atorvastatin therapy can effectively prevent the progression of coronary lesions in KD patients.
Inclusion criteria: inclusion criteria:

 Clinical diagnosis of Kawasaki Disease with giant aneurysm

 Must be older than 10 years old

Exclusion criteria: :

 Subjects ever received coronary artery bypass graft (CABG) surgery.

 Subjects have active hepatitis or persistent abnormal liver function such as elevated GOT and GPT.

 Subjects have the past history of rhabdomyolysis.

 Female subjects are pregnant or plan for child-bearing during study periods.

['Kawasaki Disease', 'Aneurysm, Coronary']


Omr-IgG-am(Trademark) for Treating Patients With or at High Risk for West Nile Virus Disease

Summary: Investigators will assess whether Omr-IgG-am(Trademark), an intravenous immunoglobulin (IVIg) containing antibodies specific for West Nile virus (WNV), is safe and well-tolerated in patients with suspected or laboratory diagnosed WNV disease. An initial estimation of efficacy will also be made.~This Phase I/II study will enroll hospitalized adults with a presumptive diagnosis of West Nile encephalitis and/or myelitis or those with a positive laboratory test for diagnosis of WNV infection who are at high risk for progressing to severe neurologic disease based on age or immunosuppression. Patients will be randomized in blocks of five to receive either Omr-IgG-am(Trademark), Polygam(Registered Trademark) S/D (IVIG containing minimal anti-WNV antibodies) or normal saline in a ratio of 3:1:1. Patients and investigators will be blinded to treatment assignments.~Patients will receive a single intravenous dose of study medication or one of two placebos. The study participants will receive 0.5 grams/kg of Omr-IgG-am(Trademark) or Polygam(Registered Trademark) S/D or a comparable volume of normal saline. All patients will be followed for safety, natural history endpoints, and efficacy. A subset of patients will have pharmacokinetic measurements of specific anti- WNV antibodies assessed following treatment.~The primary endpoints are safety and tolerability following Omr-IgG-am(Trademark) administration.~Secondary endpoints include pharmacokinetics of specific anti-WNV antibodies, mortality in confirmed WNV positive patients, and the combination of mortality and functional status at three months in both confirmed WNV-infected patients and all patients by intention to treat. This combined endpoint will be measured using four standardized measures of cognitive and functional status: the Barthel Index; the Modified Rankin Scale; the Glasgow Outcome Score; and the Modified Mini-Mental Status Examination. A comparison of outcomes will be made for the group receiving Omr-IgG-am(Trademark) versus those receiving either placebo, and between the two placebo groups. Other secondary endpoints include the proportion of patients in each group returning to pre-morbid baseline and each subject's improvement at 3 months as compared to that subject's worst (of any previous) evaluation.~Natural history endpoints will also be assessed. They will include the duration of intensive care unit (ICU) and hospital stay, development and persistence of WNV-specific IgG and IgM antibodies, combined functional score and mortality at 3 months between the group with encephalitis and/or myelitis at baseline versus the group with a positive WNV test only, outcomes in patients treated late in coma and correlation of outcome with time-to-treatment following symptom onset.
Inclusion criteria: inclusion criteria:

 In order to participate in this clinical trial, all subjects (or legal representative) must provide written informed consent. Only patients meeting entry criteria will be enrolled. Eligible subjects must fall into one of two categories:

 A. Hospitalized patients greater than or equal to 18 years of age with encephalitis and/or myelitis as defined below:

 New neurologic abnormality:

 Asymmetric extremity weakness without sensory abnormality; or

 Other neurologic abnormality (including altered level of consciousness, dysarthria and dysphagia) plus fever (subjective or objective) within the previous 4 days

 AND

 CSF examination within the previous 96 hours showing:

 Absence of organism on gram or fungal stain

 White blood cell count greater than or equal to 4 per mm(3) corrected for significant red blood cell contamination.

 Ratio of CSF: plasma glucose of greater than or equal to 40% (CSF glucose/plasma glucose greater than or equal to 0.4)

 OR

 B. Hospitalized patients without encephalitis and/or myelitis as defined below who meet the following criteria:

 A positive IgM serology or PCR test for WNV in blood or cerebrospinal fluid,

 AND

 Clinical illness compatible with WNV infection as described by occurrence of greater than or equal to 3 of the following findings during the preceding less than or equal to 10 days:

 Diarrhea, headache, fever greater than 38 degrees Celsius, nausea and/or vomiting, myalgias and/or arthralgias, nuchal rigidity, macular or papular rash, new neurological abnormality

 AND

 A risk factor for the development of WNV neurologic disease as defined by:

 Age greater than or equal to 40 years, or

 Age greater than or equal to 18 years, plus immunosuppression, as defined by any of the following:

 Hematologic malignancy, previous diagnosis of diabetes mellitus, chemotherapy within previous 4 weeks, stem cell transplant recipient or solid organ transplant recipient, taking immunosuppressive medications, including prednisone greater than or equal to 7.5 mg/day within the previous 4 weeks, history of human immunodeficiency virus (HIV) infection, congenital immunodeficiency syndrome (including common variable immunodeficiency)

Exclusion criteria: :

 Unable to obtain valid informed consent

 History of intolerance (including anaphylaxis) to IVIg or related compounds

 Known history of IgA deficiency

 Known history of hypersensitivity to maltose.

 History of (or at time of study entry) hyperviscosity syndrome including but not limited to:

 Waldenstrom's macroglobulinemia

 Multiple myeloma

 Total white blood cell count greater than 80,000/mm(3)

 Hematocrit greater than 55%

 Platelet count greater than 700,000/mm(3)

 Meets criteria of Class III or IV of the New York Heart Association Classification for congestive heart failure patients

 Serum creatinine greater than 2.5 mg/dL or requires dialysis

 Alternate explanation (as determined by the investigator) for clinical findings (such as structural brain lesion, cerebrovascular accident, or other infectious disease, including confirmed infections with other flaviviruses)

 Pregnant or breastfeeding (negative serum or urine pregnancy test within previous 72 hours if woman is not postmenopausal or has not been surgically sterilized)

 Investigator's opinion that patient would be unable to adhere to protocol requirements

 Receipt of ribavirin, interferon alpha, intravenous immunoglobulin or any investigational drug for treatment of WNV or hepatitis within 15 days prior to study entry.


A New Cochlear Implant Electrode For Inner Ear Malformations

Summary: The custom made device was produced by Med-El Company. It has a cork like stopper instead of the usual silicon ring to prevent gusher. There are two types of electrodes consisting of different length. Standard one is 25 mm (contact space 1.7 mm) and the short one is 20 mm (contact space 1.3 mm). It was used in 50 patients with different inner ear malformations. Thirteen patients had gusher, and 11 patients oozing during cochleostomy. One patient with initial prototype of the cork electrode had to be revised because of persistent oozing around the electrode. Another patient had slow extrusion of the electrode most probably due to CSF (cerebrospinal fluid) pulsation and had to be revised. Both patients had no more CSF fistula.~CSF fistula in inner ear malformations is a serious situation which may lead to recurrent meningitis. The new cochlear implant electrode with cork stopper looks promising in preventing the postoperative CSF leak around the electrode.
Inclusion criteria: inclusion criteria:

 Must have an inner ear malformation

 Must meet the criteria for cochlear implantation

Exclusion criteria: :

 Prior cochlear implantation surgery


Maastricht Neck Study: Cervical Range of Motion in Whiplash Patients

Summary: Rationale: Neck complaints are often caused by motor vehicle accidents and particular after rear-end collision. Patients complain about neck pain after a whiplash trauma, which lead to mobility restrictions of the cervical spine. It is estimated that 20% develop a chronic pain disorder after 1 year, called a chronic whiplash syndrome.~Objective: the primary objective is to investigate the natural course of active-and passive range of motion and principally the difference score between active-and passive cervical range of motion after a whiplash trauma. The secondary objectives are: investigate the predictive value of active-and passive range of motion and chronicity. Further, the correlation between the degree of restriction of the active and passive backward flexion and chronicity will be investigated. Finally, the correlation between the possible predictive factors such as pain, ideas and feeling about pain, memory and attention, events of the last year and complaints after the motor vehicle accident and chronicity are examined.~Study design and study population: a prospective cohort of 100 whiplash patients which underwent a measurement of the cervical movements and gave permission to recontact them for further research.
Inclusion criteria: inclusion criteria:

 Patients have had a measurement of the cervical range of motion.

Exclusion criteria: :

 None.


The Congestive Heart Failure Adherence Redesign Trial

Summary: The purpose of this study is to test whether a culturally sensitive self-management (SM) intervention, compared to an education only control, will reduce all-cause hospital days in patients with mild to moderate heart failure and household income less than $30,000 per year.
Inclusion criteria: inclusion criteria:

 inclusion criteria (PCP) 1. Provider must be the health professional who is managing the potential patient enrollee's heart failure medication(s).

 inclusion criteria (Patients)

 Participant has been diagnosed with Heart Failure (HF),

 Self reported family income is less than $30,000/year,

 Has experienced at least one hospitalization for acute, decompensated, HF within the previous 6 months based upon:

 Being admitted for symptoms of HF (ex: peripheral edema, shortness of breath and fatigue), and

 responding to anti-failure therapy such as diuretics and other anti-failure therapy such as ACE Inhibitors, ARBs, or Beta blockers.

 Has evidence of systolic dysfunction, defined by an ejection <50 by 1 of 3 methods: echocardiography, radiographic contrast ventriculography, or nuclear ventriculography; done within the last year.

 Age ≥ 18 years

 Currently resides in Cook County, Illinois.

 Speaks English or Spanish.

 The primary care provider (PCP) has consented and has no more than 12 patients enrolled.

 Completed the informed consent process.

 Successfully completed the 30-day run-in period and study baseline visit

Exclusion criteria: :

['Enhanced Training', 'Enhanced Education']

['Heart Failure, Congestive', 'Cardiovascular Diseases', 'Heart Diseases']

Heart Failure
Congestive
Cardiovascular Diseases
Heart Diseases


Biomarker Expression in Tissue Samples From Patients With Bone Sarcomas

Summary: This trial studies biomarker expression in tissue samples from patients with bone sarcomas. Studying biomarker in tissue samples from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer
Inclusion criteria: inclusion criteria:

 Tissue samples from patients with osteosarcomas obtained from the CHTN:

 P9754 clinical trial for patients with non-metastatic osteosarcoma

 AOST0121 clinical trial for patients with metastatic or recurrent osteosarcoma
Exclusion criteria:

['Localized Osteosarcoma', 'Metastatic Osteosarcoma', 'Recurrent Osteosarcoma']

Localized Osteosarcoma
Metastatic Osteosarcoma
Recurrent Osteosarcoma


Sleep Apnea Syndrome and Community Acquired Pneumonia

Summary: The association of sleep apnea-hypopnea syndrome (SAHS) with the infections of the lower airway has not been studied. The aspiration of secretions of the upper airway and the colonization by microorganisms is considered a main event in most of the cases of community acquired pneumonia (CAP) , and specially in the nosocomial pneumonia. The silent aspiration to the lower airway is a common phenomenon in normal subjects during the sleep and some studies has reported that the patients with SAHS present an increase of the risk to pharyngeal aspirations. In fact, the presence of nasal and bronchial inflammation in patients with SAHS is a recognized event. The patients with SAHS could have a risk increased to develop pneumonia due to predisposition to the pharyngeal microaspiration to lower airways during the sleep and other mechanical factors associated. The prevalence of SAHS in patients with CAP could be increased as regards the data published for the same Spanish population. The presence of an apnea-hypopnea index (AHI) could be a risk factor not only to to CAP but to to present a unfavorable clinical evolution in comparison to patients with CAP with a normal AHI. The aim of this study will establish a relation between SAHS and the pneumonia risk.
Inclusion criteria: Group A:

 inclusion criteria:

 Hospital admission and Community acquired pneumonia

Exclusion criteria: :

 Nosocomial infections

 Low level of conscientiousness

 Neurological disease

 Impossibility to complete the questionnaires

 Group B

 inclusion criteria:

 Hospital admission and other infections different to respiratory infections

['Sleep Apnea Syndrome', 'Polygraphy', 'Community Acquired Pneumonia', 'Infections']

Sleep Apnea Syndrome
Polygraphy
Community Acquired Pneumonia
Infections


The Relationship Between Allergic Rhinitis and Geographic Tongue

Summary: Allergic rhinitis is a complex chronic inflammatory disease, it always presents with nasal obstruction, nasal itching, sneezing and runny nose. Whether in adults or children, rhinitis is a complex disease. The prevalence of allergic rhinitis in Taiwan is about 24-29%. Taiwan is a developing country. It is a hot and humid country. In developing countries, industrialization, air pollution makes the constantly increasing number of patients with rhinitis. Penghu in 1994 for children aged 7 to 14 by the study found that among 7599 people, 1766 people have allergic rhinitis, about 23.2%. Allergic rhinitis is a complex chronic disease. So, it become a diagnostic challenge, its prevalence always underestimated. The prevalence of rhinitis has increased in recent years. The phenomenon of underestimate is caused by variety of personal and environmental factors. Allergic rhinitis had increased direct and indirect social and economic burden.~Geographic tongue is a benign tongue performance. Geographic tongue has been reported their relevance to allergy. Geographic tongue is a chronic tongue situation. The causes of geographic tongue still remains unknown. Allergic rhinitis is a diagnostic challenge to clinicians. The investigators hope that geographic tongue could play a role in the diagnostic of allergic rhinitis. The prevalence of geographic tongue in the United States is about 1.8%, white Americans and Mexicans have a higher incidence rate. This study will investigate the relevance between allergic rhinitis and geographic tongue. The investigators will analyze the relevant gender, age, severity of inspection reports. The research results wound provide an important reference to the diagnosis of allergic rhinitis.
Inclusion criteria: inclusion criteria:

 rhinitis and non-rhinitis patients

 willing to complete the study

 no limitation of tongue movement

Exclusion criteria: :

 more than 90 years old or younger than 20 years old

 unable to complete the study

['Allergic Rhinitis', 'Geographic Tongue']


Prevention of Seasonal Affective Disorder

Summary: This is a placebo controlled study evaluating the effectiveness of medication in preventing depressive episodes in subjects with a history of Seasonal Affective Disorder (SAD).
Inclusion criteria: inclusion criteria:

 Patient has a history of Major Depressive Disorder (MDD) with a seasonal pattern.

Exclusion criteria: :

 Patient has a current or past history of seizure disorder or brain injury.

 Patient has a history or current diagnosis of anorexia nervosa or bulimia.

 Patient has recurrent summer depression more frequently than winter depression.

 Patient has primary diagnosis of panic disorder, Obsessive Compulsive Disorder (OCD), Posttraumatic Stress Disorder (PTSD), acute distress disorder, bipolar II disorder or other psychotic disorders.

 Patient has initiated psychotherapy within the last 3 months.


Ceritinib in Mutation and Oncogene Directed Therapy in Thyroid Cancer

Summary: This is an, open-label, protocol designed to evaluate the activity of targeted therapy in anaplastic/undifferentiated thyroid cancer. Arm A will evaluate ATC/UTC with mutations or rearrangements detected in the ALK gene.~There is no effective treatment for anaplastic thyroid cancer in the locally recurrent or metastatic setting. Ceritinib will be administered to the patient until disease progression by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason.~The primary focus of this arm of the protocol is identifying ceritinib's activity in anaplastic or undifferentiated thyroid cancer patients. Those patients with mutations identified in their ALK gene by sequencing their tumor samples, or with the established ALK abnormalities will be treated with ALK-inhibitors. These include the Ventana assay and Vysis FISH probe, and patients with tumors positive by this assay will also be considered eligible for therapy on the trial.~Therapeutic Portion:~ARM A: ALK Abnormality IND Ceritinib 750 mg orally daily on Day 1 Continue q4 weeks x 2 cycles~Primary Endpoint: The development of progression; new recurrence or distant metastasis, as well as enlargement of an existing metastasis on radiographic imaging.~Secondary Endpoints:~Overall response rate for patients treated with ceritinib as part of the study.~Death of study participant due to any cause.
Inclusion criteria: inclusion criteria:

 Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or undifferentiated thyroid cancer that demonstrates mutation in the ALK gene as assessed by sequencing of the tumor specimen for Arm A. Other ALK abnormalities as detected by the approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana IHC test will also be seen as evidence of ALK abnormality and meeting eligibility requirement.

 Patients will not have any other curative therapeutic option, such as radiation or surgery.

 WHO performance status 0-2.

 Age greater then or equal to 18 years.

 Patients must have recovered from all toxicities related to prior anticancer therapies to ≤ Grade 2 (CTCAE v 4.03), provided that any concomitant medication is given prior to initiation of treatment with ceritinib. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.

 Adequate organ function: the following laboratory criteria have been met:

 Absolute neutrophil count (ANC) greater then or equal to 1.5 x 109/L

 Hemoglobin (Hgb) ≥ 8 g/dL

 Platelets greater then or equal to 75 x 109/L

 Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), except for patients with Gilbert's syndrome who may be included if total bilirubin ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN

 Aspartate transaminase (AST) < 2.0 x ULN, except for patients with liver metastasis, who are only included if AST < 3 x ULN; alanine transaminase (ALT) < 2.0 x ULN, except for patients with liver metastasis, who are only included if ALT < 3 x ULN

 Calculated or measured creatinine clearance (CrCL) less then or equal to 30 mL/min

 Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits at screening:

 Potassium ≥ LLN

 Magnesium ≥ LLN

 Phosphorus ≥ LLN

 Total calcium (corrected for serum albumin) ≥ LLN

 Written informed consent for the protocol must be obtained prior to any screening procedures.

 Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion criteria: :

 Patients eligible must not meet any of the following criteria:

 Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).

 Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry to manage CNS symptoms.

 Prior therapy with ceritinib.

 Presence or history of a malignant disease other than thyroid cancer that has been diagnosed and/or required therapy within the past year and is undergoing active anticancer treatment. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.

 Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention).

 Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:

 unstable angina within 6 months prior to screening;

 myocardial infarction within 6 months prior to screening;

 history of documented congestive heart failure (New York Heart Association functional classification III-IV);

 uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication

 initiation or adjustment of antihypertensive medication(s) is allowed prior to screening;

 ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication;

 other cardiac arrhythmia not controlled with medication;

 corrected QTc > 450 msec using Fridericia correction on the screening ECG

 Impaired GI function or GI disease that may alter absorption of ceritinib or inability to swallow up to five ceritinib capsules daily.

 Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the study.

 Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of participation (see Appendix 1 Tables):

 Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm)

 Strong inhibitors or strong inducers of CYP3A4/5 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)

 Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)

 Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban).

 Unstable or increasing doses of corticosteroids

 enzyme-inducing anticonvulsive agents

 herbal supplements

 Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

 Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and agree to continue for 3 months after the last dose of study treatment. Highly effective contraception methods include:

 Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

 Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.

 Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. For female subjects on the study the vasectomized male partner should be the sole partner for that subject.

 Combination of any two of the following (a+b or a+c or b+c):

 Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.

 Placement of an intrauterine device (IUD) or intrauterine system (IUS).

 Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

 In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

 Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

 Sexually active males unless they agree to use a condom during intercourse while taking drug and agree to continue for 3 months after the last dose of study treatment. Male patients for 3 months should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

['Metastatic Anaplastic Thyroid Cancer', 'Locally Advanced Anaplastic, Undifferentiated Thyroid Cancer']

Metastatic Anaplastic Thyroid Cancer
Locally Advanced Anaplastic
Undifferentiated Thyroid Cancer


Nebulized Colistin for Hospital-Acquired Pneumonia

Summary: Nebulized Colistin for Adjunctive Therapy of Hospital-Acquired Pneumonia caused by Gram Negative Bacteria should be more effective than conventional therapy
Inclusion criteria: inclusion criteria:

 Adult (age>18 years) hospitalized patient with hospital-acquired pneumonia due to Gram negative bacteria

Exclusion criteria: :

 pregnancy

 lactating woman

 colistin allergy

 severe renal impairment

 epilepsy


Comparison of Long- and Short-acting Diuretics in Congestive Heart Failure

Summary: The purpose of this study is to compare therapeutic effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in patients with heart failure, and to test our hypothesis that long-acting diuretics are superior to short-acting types in heart failure.
Inclusion criteria: inclusion criteria:

 Clinical diagnosis of heart failure based on a slight modification of the Framingham criteria as previously described within 6 months before the entry

 Current status of heart failure is NYHA II or III.

 Currently, loop diuretic(s) is (are) administered.

 No change in baseline therapy and symptoms of heart failure within a month

Exclusion criteria: :

 Current symptomatic hypotension

 Hypertension that has not been controlled to the satisfaction of the investigator

 Hemodynamically significant (in the investigators opinion) LV outflow tract obstruction (due to either aortic stenosis or ventricular hypertrophy)

 Acute coronary syndrome

 Primary pulmonary hypertension or pulmonary hypertension not due to LV dysfunction

 Serious cerebrovascular disease

 Acute myocardial infarction within the last 3 months

 Patients who require intravenous inotropes

 Cerebrovascular accident within the last 3 months

 Percutaneous coronary intervention or open heart surgery within the last 3 months

 On the waiting list for percutaneous coronary intervention or open heart surgery

 Serum creatinine > 2.5 mg/dl

 Serious liver disease

 Any change in cardiovascular drug therapy within a month prior to randomization

 History of chronic obstructive pulmonary disease or restrictive lung disease

 Diabetes mellitus that has not been well controlled (fasting blood glucose>200 mg/dl、HbA1c > 8%)

 Any life-threatening acute disease

 Patients with implantable cardiac defibrillator

 Other diseases likely to cause death or serious disability during the period of the study

 Patients unable to walk without personal aid


Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency

Summary: The objective of this study is to assess the efficacy and safety of Vivaglobin in previously untreated patients (PUPs) with primary immunodeficiency (PID) over a 25-week observation period. The purpose is to investigate whether PUPs will respond to subcutaneous immunoglobulin (SCIG) treatment with adequate trough levels without first receiving immunoglobulins by the intravenous route by demonstrating that 100 mg immunoglobulin G/kg body weight (IgG/kg bw) administered on 5 consecutive days (i.e. resulting in a total dose of 500 mg IgG/kg bw) results in an IgG increase to ≥ 5 g/L on Day 12 after initiation of SCIG therapy.
Inclusion criteria: Key inclusion criteria:

 Written informed consent, age-adapted

 Male or female aged 1 to 70 years

 Diagnosis of primary humoral immunodeficiency

 No prior immunoglobulin substitution therapy

 IgG level of <5 g/L at screening

 Women of childbearing potential must use medically approved contraception and must have a negative urine pregnancy test at screening

 Key
Exclusion criteria: :

 Evidence of serious infection between screening and first treatment

 Bleeding disorders that require medical treatments

 Any medical disorder causing secondary immune disorders, autoimmune neutropenia, or a clinically significant defect in cell mediated immunity

 Any condition likely to interfere with evaluation of the study drug or satisfactory conduct of the trial

['Common Variable Immunodeficiency', 'Agammaglobulinemia']

Common Variable Immunodeficiency
Agammaglobulinemia


The Use of Functional Confections in Promoting Oral Health

Summary: In areas of the world where populations are undernourished poor oral health is prevalent. Diets rich in fruit and vegetables are thought to have many health benefits including reducing the risk of oral cancer or gum disease. In particular fruits such as strawberries contain many different compounds which may be responsible for these proposed health benefits.~From this study, the researchers hope to gain information about how the tissues in the mouth absorb strawberry gummies in a population of habitually smoking and never smoking men and women. The researchers will measure inflammation hormones in your saliva and urine and the genes in your mouth and blood. Two different strawberry gummies will be tested in this study. The strawberry gummies were developed at OSU in the Department of Food Science and Technology. One type of strawberry gummy will contain freeze-dried whole strawberries while the other type will have no fruit. In total the eight pieces of strawberry gummies that you will consume in one day will be at most equal to 1 cup of whole strawberries. The research team believes the two strawberry gummies may be digested and absorbed differently and that components in the strawberry gummies may be helpful for oral health.
Inclusion criteria: inclusion criteria:

 Submit to a 24 hour urine cotinine test which will be used to determine smoking status.

 Meet one of the following smoking criteria

 Non-smoker

 Does not currently smoke or has no history of smoking or using tobacco related products (cigarettes, cigars, pipe, snuff, or chewing tobacco) or smoking any non-tobacco related products and urine cotinine (less than 100 ng/mL

 Does not currently smoke but has quit smoking for more than 10 years and smoked less than 1 pack/day of cigarettes when they were actively smoking and has a urine cotinine (less than 100 ng/mL).

 Smoker

 Smokes habitually at least 10 cigarettes/day and a urine cotinine level of >1000 ng/mL. Cigar and pipe smokers who smoke at least 10 grams of tobacco daily are also eligible.

 Agree to consume a standardized vitamin and mineral supplement and avoid other nutritional, dietary, or alternative medications/supplements for the duration of the study.

 No history of malabsorptive, gastrointestinal or other metabolic disorders requiring special diet recommendations.

 Body mass index (BMI) between 20 and 35 kg/m2

 Abstain from purple and red colored foods and beverages which contain significant anthocyanins and polyphenols

 Abstain from the use of ANY mouth washes (commercial or home remedies)during 6 week study period

Exclusion criteria:

 Have a known allergy to strawberries, corn, and wheat products or those who have never consumed any of these products.

 Have active metabolic or digestive illnesses such as malabsorptive disorders (Crohn's, ileus, IBS), renal insufficiency, hepatic insufficiency, hyper- or hypothyroidism, cachexia, morbid obesity, or short bowel syndrome.

 Have a history of pituitary hormone diseases that currently require supplemental hormonal administration (thyroid hormones, ACTH, growth hormone, insulin) or other endocrine disorders requiring hormone administration.

 Have significant loss of gastrointestinal organs due to surgery, except for appendix.

 Have altered immunity such as chronic inflammatory disease, autoimmune disorders, cancer, anemia, hemophilia, and blood dyscrasias.

 Heavy alcohol consumers defined as >15 glasses/week (one glass = 1.5 oz. liquor, 5 oz. wine, or 12 oz. beer).

 Antibiotic use in the last 6 months or on medications that will accelerate or decrease bowel motility.

 Are receiving or in need of dental treatment during the study period.

 Have noticeable open lesions, sores that have not healed for more than 3 months, have had any active oral lesions or maladies within the last month, or have a history of leukoplakia, tumors of the buccal cavity, throat, and lips.

 Have difficulty swallowing (dysphagia), pain with swallowing (odynophagia), salivary gland dysfunction, or xerostomia (dry mouth).

 A non-smoker who is currently or has a history (less than 10 years of smoking abstinence) of either tobacco or non-tobacco related smoking.

 Women, who are planning to conceive in the next 6 months, suspect they are pregnant, pregnant, or nursing.

 Are taking medications that inhibit clotting (warfarin sodium) or using prescribed oral rinses (Peridex).

['Strawberry gummy', 'Placebo control gummy']

['Oral Health', 'Oral Cancer', 'Gum Disease']


Positive Action for Today's Health

Summary: Regular moderate and vigorous intensity physical activity (PA) is inversely related with obesity, however, few adults are successful in incorporating sufficient PA into their daily lives. Minority and lower-income adults have among the highest obesity rates and lowest levels of regular PA. Increasing environmental supports for safe and convenient places for PA is an emerging public health strategy for PA interventions. Preliminary data by Wilson (PI) and colleagues has revealed through focus groups that low-income minority adults would like to increase the safe places for PA (areas free from crime, containment of stray dogs, increased police patrol) and access to PA (sidewalks/trails and expand opportunities for PA) in their community. In addition, the results of the investigators' preliminary studies suggest that African Americans had psychosocial barriers to PA that included lack of self-motivation, cultural body image issues, and lack of time due to family obligations. The present proposal is innovative in that it specifically tests the efficacy of an intervention that includes both patrolled-walking and social marketing elements to increase PA in low-income African Americans. Three communities will be randomized to receive one of three programs: a police patrolled-walking program plus social marketing intervention, a police patrolled-walking only intervention, or no walking intervention (general health education only; N=390; 130/group). The 24-month intervention will focus on increasing safety (training community leaders to serve as walking captains, hiring off-duty police officers to patrol the walking program, and containing stray dogs), increasing access for PA (marking a walking route), and will include a tailored social marketing campaign for increasing PA (in one intervention community). The investigators will collect data for PA (7-day accelerometer estimates, 4-week PA history), body composition, blood pressure, psychosocial measures, and perceptions of environmental supports for safety and access for PA at baseline, 6-,12-,18-, and 24-months. The primary hypotheses are that the patrolled-walking plus social marketing intervention will result in greater increases in moderate and vigorous PA as compared to a patrolled walking only intervention or no-intervention by 12-months and that these effects will be maintained at 18-month and 24-month assessments.
Inclusion criteria: inclusion criteria:

 African American (3 of 4 grandparents are of African Descent)

 Lives in designated census area

 No plans to move in the next two years

 Has no medical condition that would limit participation in moderate intensity exercise including life-threatening illness (e.g., immobile, severely disabled, or bed ridden)

 Available and able to participate in measures and intervention activities over the next 2 years

Exclusion criteria: :

 Extreme Blood Pressure and/or Blood Glucose levels

 Unable to take a brisk, 30-minute walk

['Police Patrolled Walking plus Social Marketing', 'Police Patrolled Walking Program Only', 'General Health Education']


A Phase 1 Study To Estimate The Effects Of PD 0332334 On Lithium Pharmacokinetics In Healthy Subjects

Summary: The purpose of this study is to investigate if PD 0332334 affects the pharmacokinetics of lithium by co-administering both drugs to healthy adults.
Inclusion criteria: inclusion criteria:

 Healthy males and/or females

 Age from 21 to 55 (inclusive)

 BMI ranges from 18 to 30 kg/m2

Exclusion criteria: :

 Previous participation in a PD 332334 study

 Pregnant or nursing females

 Hypersensitivity (allergic) to lithium, Neurontin (gabapentin), or Lyrica (pregabalin)


A Trial of Low Dose Sulindac Combined With Eflornithine in Patients With Familial Adenomatous Polyposis (FAP)

Summary: The purpose of this phase III study is to evaluate the safety and efficacy of the combination of eflornithine and sulindac compared to single agent sulindac or eflornithine in reducing the number of polyps in patients with familial adenomatous polyposis (FAP).
Inclusion criteria: inclusion criteria:

 Diagnosis of phenotypic Familial Adenomatous Polyposis (FAP) of the colorectum based on meeting the criteria in one of two groups: Group 1-Greater than 100 adenomatous colorectal polyps prior to age 40. Group 2-Greater than 10 adenomatous polyps and age <40 or greater than 25 polyps and age >40; combined with a dominant family history or genotype: More than 100 polyps in a first-degree relative; More than 25 polyps in 2 relatives in 2 generations, including a first-degree family member; Genetic diagnosis in a relative; Genetic diagnosis by in vitro synthesized truncated protein or similar assay.

 No colorectal surgery or prior colon surgery for polyposis at least 1 year prior (total abdominal colectomy with ileal-rectal anastomosis, or total proctocolectomy with ilea pouch-anal reconstruction.

 Baseline endoscopy

 If no prior colorectal surgery, at least 3 polyps in a cluster each ≥ 2 mm in diameter; or

 If rectum is in situ and to be assessed, baseline rectal segment endoscopy documenting 3 or more rectal polyps each at least 2 mm in diameter in a defined cluster and/or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of rectum

 If ileal pouch neo-rectum is in place, 3 or more pouch polyps in a cluster ≥ 2 mm in diameter, or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of pouch.

 Clinical/pathological grading of duodenal polyps will utilize the Spigelman Classification.

 Hematopoietic: no significant hematologic dysfunction; WBC ≥3,000/mm3; platelet count ≥100,000/mm3; hemoglobin ≥10g/dL; no known or prior clinical coagulopathy.

 Hepatic: bilirubin ≤ 1.5 times ULN; AST and ALT ≤ 1.5 times ULN; Alkaline phosphatase ≤ 1.5 times ULN.

 Renal: No significant renal dysfunction; creatinine ≤ 1.5 times ULN.

 Hearing: no clinically significant hearing loss that affects everyday life.

 Not pregnant or nursing.

 Negative serum pregnancy test if female of child-bearing potential.

 Absence of gross blood in stool.

 Fertile patients must use effective contraception.

 Stool occult blood either negative or minimal (1+).

 No prior hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates; no NSAID associated symptoms of gastritis.

 No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated successfully with antibiotics (as documented by an endoscopy.

 No invasive malignancy within the past 5 years except stage I or II colon or rectal cancer or resected nonmelanomatous skin cancer.

 No other significant medical or psychiatric problems that would preclude study participation.

 No chronic adrenocorticosteroids.

 No prior pelvic irradiation.

 At least 3 months since prior investigational agents.

 Patients may not be receiving or plan to receive corticosteroids.

 Concomitant NSAID use outside this study may not exceed 4 days per month.

 Use of 81 mg daily aspirin or 650 mg aspirin not more than once a week.

 No concurrent warfarin, fluconazole, or lithium.

 Must be willing and able to sign informed consent.

Exclusion criteria: :

 High Risk for cardiovascular disease including clinical diabetes mellitus (Type I or II) requiring glycemic medications; Prior personal history of cardiovascular disease or, two or more of the following - hypertension or use of anti-hypertensive medications, hyperlipidemia or use of lipid-lowering medications or current smoker.

 Hearing loss that affects everyday life and or for which a hearing aid is required.

['Eflornithine plus Sulindac', 'Eflornithine plus Placebo', 'Sulindac plus Placebo']

Eflornithine plus Sulindac
Eflornithine plus Placebo
Sulindac plus Placebo


Efficacy of AC-170 for the Treatment of Allergic Conjunctivitis in the Conjunctival Allergen Challenge (CAC) Model

Summary: The purpose of this study is to evaluate the efficacy of different concentrations of AC-170 compared to vehicle in the prevention of the signs and symptoms of allergic conjunctivitis in the conjunctival allergen challenge (CAC) Model.
Inclusion criteria: inclusion criteria:

 Positive bilateral conjunctival allergen challenge (CAC) reaction

Exclusion criteria: :

 Known contraindications or sensitivities to the study medication or its components.

 Any ocular condition that, in the opinion of the investigator, could affect the subjects safety or trial parameters.

 Use of disallowed medications during the period indicated prior to the study enrollment or during the study.


Myfortic Versus Azathioprine in Systemic Lupus Erythematosus

Summary: This study is designed to explore the use of myfortic ® in patients with active lupus erythematosus. Similar drugs in this class are increasingly used in organ transplantation and in autoimmune diseases. With the established safety profile of myfortic ® in allo-transplantation and the already existing data of mycophenolate mofetil in autoimmune diseases, this study should help to demonstrate the beneficial effect of myfortic ® on lupus activity. The aim of the study will be to show a decreased disease activity with myfortic ® compared to standard maintenance therapy with azathioprine.
Inclusion criteria: inclusion criteria:

 Males or females, aged 18 years and over

 Patients meeting the diagnostic criteria for SLE (Appendix 2), according to ACR guidelines (including screening for anti-dsDNA (antibody to native DNA in abnormal titer))

 SLEDAI > 6

 Patients treated with maintenance therapy including azathioprine.

 Patients who are willing and able to participate in the study and from whom written informed consent has been obtained

Exclusion criteria: :

 Creatinine clearance of < 20ml/min

 Patients with any clinically significant infection

 Patients with known hypersensitivity to myfortic ® or to drugs with similar chemical structures

 Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin

 Patients with SLE active CNS manifestations or a past history of SLE CNS complications (e.g. psychosis, grand mal seizures)

 Patients who have received prior therapy with mycophenolic acids (MPAs) (e.g. MMF)

 Patients who have received an investigational drug within four weeks prior to study entry

 Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception

['switch to Myfortic', 'continuation of azathioprine']

switch to Myfortic
continuation of azathioprine


MoodHelper: Internet Cognitive Behavioral Therapy (CBT) for Depression

Summary: Evidence-based treatments (EBTs) for mental health conditions are often not available to persons needing them in the community. Our aim is to test a novel Internet intervention that has the promise of eventually improving the Reach and Implementation of mental health EBTs, speeding the translation of research successes into improved community care.
Inclusion criteria: inclusion criteria:

 Participants must have a score ≥ 10 on the self-report Patient Health Questionnaire (PHQ-8), indicative of clinically significant, moderate depression.

 Participants must identify their primary healthcare provider in one of the 8 performance sites, and give permission to contact him or her for the purpose of periodic progress reports as well as a referral contact in case any emergent crises are detected.

 Participant must be 18 years of age have access to a computer with internet and a working email address.

 Participants must also indicate they are planning to continue receiving services from one of the performance site clinics/organizations for at least the next 6 months
Exclusion criteria:

['Pure self-help Internet CBT for depression', 'Guided self-help Internet CBT', 'Stepped-Care Internet CBT condition']


Optimization of Mass Drug Administration With Existing Drug Regimens for Lymphatic Filariasis and Onchocerciasis for Ivory Coast (DOLF-Ivory Coast)

Summary: Approximately 4,000 people will participate per year. The study population will include females and males over 5 years of age who live in filariasis and onchocerciasis endemic areas. Subject selection will not be based on health status.~Two sites will be studied, and each study will last for 4 years. Participants will be studied only once in cross-sectional surveys. Some subjects may be included in more than one annual population survey, but this is not a longitudinal study.~Investigators will compare annual and semiannual mass drug administration (MDA) for lymphatic filariasis and onchocerciasis, and investigators will compare the impact of these MDA schedules on soil transmitted helminth infections. MDA will be administered by others (Ivorian Ministry of Health).~The investigators will test the hypothesis that semiannual mass drug administration (MDA) is superior to annual MDA for elimination of lymphatic filariasis, onchocerciasis and for control of soil transmitted helminth (STH) infections.~Compare the relative impact and cost effectiveness of annual vs. twice yearly mass drug administration (MDA) for elimination of lymphatic filariasis (LF) in these populations.~Compare the relative impact and cost effectiveness of annual vs. twice yearly mass drug administration (MDA) for elimination of onchocerciasis in these populations.~Study the impact of annual vs. semiannual MDA on soil transmitted helminth (STH) infection in these populations.
Inclusion criteria: inclusion criteria:

 Study areas should be endemic for filariasis and onchocerciasis.

 Study population have limited or no prior experience with MDA. Males and Females greater than or equal to 5 years of age.

Exclusion criteria: :

 Children less than 5 years of age.

 Children who weigh less than 15 kg (33 lb)

['Annual versus Semiannual Albendazole plus Ivermectin MDA']

['Lymphatic Filariasis', 'Onchocerciasis', 'Soil Transmitted Helminth (STH) Infections']


Enteroaggregative E.Coli (EAEC)

Summary: Enteroaggregative E. coli (EAEC) is a bacterium that can cause diarrhea. The purposes of this study are to: determine how much EAEC is needed to cause diarrhea in a healthy person, determine if a genetic factor is important in causing diarrhea, and to see how the body's defenses control EAEC. Participants include 25 healthy adults, ages 18-40. Volunteers will be assigned to 1 of 4 dose levels in groups of 5 volunteers each. One volunteer in each group will receive a sodium bicarbonate placebo solution. Volunteers will be admitted to the University Clinical Research Unit for up to 8 days. Volunteers will receive therapy with levofloxacin to treat the infection either once they develop diarrhea or at Day 5 if they remain asymptomatic. Study procedures will include saliva, blood, and fecal sample collection. An optional study procedure will include an intestinal biopsy. Participants will be involved in study related procedures for up to 223 days.
Inclusion criteria: inclusion criteria:

 Sign an Institutional Review Board-approved consent prior to any study-related activities.

 Initiate screening 21± 7 days prior to admission or enrollment.

 Must accomplish all laboratory and diagnostic examinations at 21± 7 days prior to admission or enrollment.

 Be at least 18 years of age but not older than 40 years of age at the time of enrollment.

 Be otherwise healthy with a stable address and telephone where the volunteer can be contacted.

 Be able to read and write English.

 Possess a social security number in order to receive compensation.

 Female participants must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the morning of the challenge and use effective birth control during the entire study period. Methods of effective birth control include: complete abstinence, the use of a licensed hormonal method, intrauterine device, barrier method plus spermicide, or having sexual relations exclusively with a vasectomized partner. Appropriate barrier methods include condoms, cervical sponge, and diaphragm. Females who are not of childbearing potential are defined as those who are physiologically incapable of becoming pregnant, including any female with tubal ligation or who is postmenopausal. For purposes of this study, postmenopausal status will be defined as absence of menses for at least 1 year.

 Be seronegative for antibodies to dispersin.

 Have normal laboratory screening values including a white blood cell (WBC) count, hemoglobin, hematocrit, platelets, blood urea nitrogen, glucose, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), quantitative immunoglobulins, T cell subsets (CD4 and CD8), urinalysis.

 Have normal chest x-ray and electrocardiogram.

 Have negative serologies for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV), and a negative rapid plasma reagin (RPR).

 Have a negative stool examination for pathogenic ova and pathogenic parasites, and bacterial enteropathogens (EAEC, Salmonella, Shigella, Campylobacter).

 Have the -251 AA IL-8 genotype.

Exclusion criteria: :

 Has acute or chronic medical illness (i.e., renal or hepatic disease, hypertension, diabetes mellitus, coronary artery disease, malnutrition, obesity (body mass index >30 kg/m2), HIV, corticosteroid use, cancer or receiving chemotherapy, chronic debilitating illness, syphilis).

 Has used antibiotics within 7 days of challenge.

 Has used medications or drugs, including over-the-counter medications such as decongestants, antacids (calcium carbonate or aluminum-based antacids, H2 blockers), anti-diarrheal medications (such as bismuth subsalicylate or loperamide), antihistamines within 7 days of challenge.

 Has a history of chronic gastrointestinal illness, intra-abdominal surgery, chronic functional dyspepsia, chronic gastroesophageal reflux, documented peptic ulcer disease, gastrointestinal hemorrhage, gallbladder disease, inflammatory bowel disease (Crohn's and ulcerative colitis), diverticulitis, irritable bowel syndrome or frequent diarrhea.

 Has a history any of the following psychiatric illness(es):

 Depression not controlled with current drug therapy or involving institutionalization

 Schizophrenia or psychosis

 Suicide attempt.

 Has a history of or current alcohol or illicit drug abuse.

 Is unable to remain as an inpatient in the University Clinical Research Unit for up to 8 days.

 Has a known hypersensitivity to latex, heparin, opiates, antiemetics, benzodiazepines, lidocaine, magnesium citrate, or Fleet enema.

 Has a known hypersensitivity to antibiotics that could be used to treat EAEC infection including fluoroquinolones, amoxicillin, cephalosporins or rifaximin.

 Has serum antibodies to EAEC dispersin.

 Recently traveled to a developing country (within 6 months).

 Has household contacts who are less than 4 years of age or more than 80 years of age.

 Has household contacts that are infirmed or immunocompromised due to any of the following reasons:

 Corticosteroid therapy

 HIV infection

 Cancer chemotherapy

 Other chronic debilitating diseases.

 Works as health care personnel with direct patient care.

 Works in a day care center for children or the elderly.

 Is a food handler.

 Has factors that, in the opinion of the investigator or research personnel, would interfere with the study objectives or increase the risk to the volunteer or his contacts.

 Is currently participating in a clinical study or had receipt of an investigational drug in the past 30 days.

 Is pregnant or has a risk of pregnancy or is lactating.

 Has current excessive use of alcohol or drug dependence.

 Has evidence of impaired immune function.

 Has a new positive reaction to purified protein derivative (PPD) (volunteers who are known to be PPD positive that have a negative chest x-ray and have received isoniazid prophylaxis will be eligible).

 Has a stool culture that demonstrates the presence of pathogenic ova, pathogenic parasites, or bacterial enteropathogens (EAEC, Salmonella, Shigella, and Campylobacter), or that is devoid of normal flora.

 Has self-reported lactose or soy intolerance or allergy

 Is a smoker and cannot stop smoking for the duration of the inpatient study.

 Has abnormal lab results for screening beyond the normal range as defined below:

 Hematology Hemoglobin: 13-15.0 gm/dL (Females) 14.5-17.0 gm/dL (Males) Hematocrit: 37-46 % (Females) 40-52 % (Males) Platelet count: 140,000-415,000 per mm3 WBC count: 4,000-10,500 per mm3 Neutrophils: 40-74 % or 1,800-7,800 per mm3 Lymphocytes: 14-26 % or 700-4,500 per mm3 Monocytes: 4-13 % or 100-1,000 per mm3 Eosinophils: 0-7 % or 0-400 per mm3 Basophils: 0-3 % or 0-200 per mm3

 Chemistry BUN 5-25 mg/dL Creatinine 0.5-1.4 mg/dL Glucose (fasting) 69-99 mg/dL ALT 0-40 U/L AST 0-40 U/L

 Immunology IgG: 596-1584 mg/dL IgA: 71-350 mg/dL IgM: 35-213 mg/dL CD4 T cells: 660-1500 cells/mcl CD8 T cells: 360-850 cells/mcl

 Urinalysis Urine color: Yellow Turbidity: Clear pH: 5.0-8.0 Protein: Negative Sp. Gravity: 1.003-1.030 Glucose: Negative WBC: 0-2 Cells per HPF RBC: 0 Cells per HPF Bacteria: Rare Ketones: Negative The urinalysis will initially be evaluated for the quality of collection. If urinalysis is found to be poorly collected and demonstrates the presence of squamous epithelial cells and bacteria, results will not be used and a repeat urinalysis will be requested. In the case of menstruating women, the urinalysis collection will be postponed temporarily. A urinalysis may also be repeated once if traces of bile, protein, trace ketones, or Hb are identified. In the case of a properly collected urinalysis, the presence of leukocyte esterase glucose, or nitrates will exclude the participation of the subject.

 Occult blood (Hemoccult) positive stools on admission to the CRU.

 Develops gastrointestinal symptoms including nausea, vomiting, anorexia, abdominal pain, cramping, bloating, excessive gas or flatulence, diarrhea, constipation, urgency or tenesmus between the screening period and prior to challenge.

 Develops a febrile illness during the period of time screening period and prior to challenge.

['Levofloxacin', 'Placebo', 'Enteroaggregative E. coli (EAEC)']

Levofloxacin
Placebo
Enteroaggregative E. coli (EAEC)


Beta-Blocker in Chronic Obstructive Pulmonary Disease (COPD) Study

Summary: Smoking causes both smoking related lung disease (COPD) and ischaemic heart disease. These are very common conditions and many patients have both diseases. Beta-blocker drugs are extensively used in the treatment of angina, high blood pressure and after heart attacks to decrease symptoms and prolong life. Beta-agonists are used in COPD to decrease breathlessness and improve exercise tolerance. It used to be thought that beta-blockers cannot be used in COPD patients as they may make the breathlessness worse, but it has now been established that they can be used safely. Beta-blocker drugs and beta-agonists have 'opposite' effects on the body and the investigators do not know if they can work together or if they would cancel each other out. The investigators also do not know which of the different types of beta-blockers now available are better for COPD patients. This study will investigate what happens to the airways of people taking both of these drugs.
Inclusion criteria: inclusion criteria:

 Clinical diagnosis of COPD

 > 40 years of age

 > 15 pack year smoking history

Exclusion criteria: :

 Contra-indication to beta-blocker use

 Severe COPD FEV1 < 30% or 1 L

 Not responsive the methacholine

['Chronic Obstructive Pulmonary Disease']


A Study to Compare Two Ways of Completing Pain and Sleep Questions and to Evaluate a New Daily Questionaire for Assessing Fatigue in Fibromyalgia Patients

Summary: The study has two goals. The first goal of the study is to compare two methods of administering questions about pain and sleep interference. The two methods being compared are a telephone based system and an electronic hand held diary. The second goal of the study is to evaluate a daily diary to evaluate fatigue symptoms in patients with fibromyalgia.
Inclusion criteria: inclusion criteria:

 Fibromyalgia using ACR diagnosis

Exclusion criteria: :

 Other confounding disease including other inflammatory disease, pain and depression

['Interactive Voice Response System (IVRS)', 'Personal Digital Assisstant (PDA)']


Angiotensin II Receptor Blockers (ARB) and ACE Inhibitors (ACEI) on Silent Brain Infarction and Cognitive Decline

Summary: The purpose of this study is to elucidate whether or not angiotensin II receptor blockers (ARB) are more beneficial or equal to angiotensin converting enzyme inhibitors (ACEI) on development or progression of silent brain infarction and cognitive decline in Japanese patients with essential hypertension in the elderly.
Inclusion criteria: inclusion criteria:

 Patients with essential hypertension (systolic blood pressure>=140 mmHg and/or diastolic blood pressure>=90, or treated with antihypertensive drugs)

 Patients with any finding of stroke, silent brain infarction, and white matter lesion on magnetic resonance imaging

Exclusion criteria: :

 Secondary hypertension

 Atrial fibrillation

 History or signs of cerebral disorders other than cerebrovascular disease

 Malignant tumor

 Chronic renal failure

 Severe congestive heart failure

 Hyperkalemia

 Stenosis of bilateral renal artery

['Angiotensin II Receptor Antagonists', 'Angiotensin-converting Enzyme Inhibitors']


Hematopoietic Stem Cell Dysfunction in the Elderly After Severe Injury

Summary: Traumatic injury is a leading cause of morbidity and mortality in young adults, and remains a substantial economic and health care burden. Despite decades of promising preclinical and clinical investigations in trauma, investigators understanding of these entities is still incomplete, and few therapies have shown success. During severe trauma, bone marrow granulocyte stores are rapidly released into the peripheral circulation. This release subsequently induces the expansion and repopulation of empty or evacuated space by hematopoietic stem cells (HSCs). Although the patient experiences an early loss of bone marrow myeloid-derived cells, stem cell expansion is largely skewed towards the repopulation of the myeloid lineage/compartment. The hypothesis is that this 'emergency myelopoiesis' is critical for the survival of the severely traumatized and further, failure of the emergency myelopoietic response is associated with global immunosuppression and susceptibility to secondary infection. Also, identifying the release of myeloid derived suppressor cells (MDSCs) in the circulation of human severe trauma subjects. This process is driven by HSCs in the bone marrow of trauma subjects. Additionally, MDSCs may have a profound effect on the nutritional status of the host. The appearance of these MDSCs after trauma is associated with a loss of muscle tissue in these subjects. This muscle loss and possible increased catabolism have huge effects on long term outcomes for these subjects. It is the investigator's goal to understand the differences that occur in these in HSCs and muscle cells as opposed to non-injured and non-infected controls. This work will lead to a better understanding of the myelopoietic and catabolic response following trauma.
Inclusion criteria: Severe Trauma Population

 inclusion criteria will be:

 All adults (age ≥18 to 54)

 Blunt and/or penetrating trauma resulting in long bone or pelvic fractures requiring ORIF or closed reduction percutaneous pinning (CRPP).

 Blunt and/or penetrating trauma patient with either:

 hemorrhagic shock defined by: i. systolic BP (SBP) ≤ 90 mmHg or ii. mean arterial pressure≤ 65 mmHg or iii. base deficit (BD) ≥ 5 meq or iv. lactate ≥ 2

 Or injury severity score (ISS) greater than or equal to 15.

 All adults (age 55 and older) require:

 Blunt and/or penetrating trauma resulting in log bone or pelvic fractures requiring ORIF or CRPP

 Either hemorrhagic shock defined by: i. Systolic BP (SBP) ≤ 90 mmHg or ii. Mean arterial pressure ≤ 65 mmHg or iii. Base deficit (BD) ≥5 meq or iv. Lactate ≥ 2

 Or Injury Severity Score (ISS) greater than or equal to 15.

 Ability to obtain Informed Consent prior to OR repair of injury.

Exclusion criteria:  will be:

 Patients not expected to survive greater than 48 hours.

 Prisoners.

 Pregnancy.

 Patients receiving chronic corticosteroids or immunosuppression therapies.

 Previous bone marrow transplantation.

 Patients with End Stage Renal Disease.

 Patients with any pre-existing hematological disease.

 Elective Hip Repair Population

 inclusion criteria will be:

 All adults (age ≥18)

 Patient undergoing elective hip repair for non-infectious reasons.

 Ability to obtain Informed Consent prior to operation.

['Bone marrow collection', 'Blood collection', 'Clinical data collection']

Bone marrow collection
Blood collection
Clinical data collection


Young Adults' Responses to Anti-smoking Messages

Summary: The purpose of this study is to determine whether anti-smoking messages based on promising smoking-related beliefs increase anti-smoking intentions more than messages based on less-promising beliefs. Never smokers and former smokers will be randomly assigned to view different anti-smoking messages, and will answer questions measuring smoking-related beliefs, intentions, and message ratings online.
Inclusion criteria: inclusion criteria:

 U.S. participants 18-25 years of age who are part of the Survey Sampling International (SSI) panel

 Never smoker (never puffed a cigarette) or former smoker (have at least puffed a cigarette but have not smoked in the past 30 days)

Exclusion criteria: :

 Less than 18 or greater than 25 years of age

 For the main study, they must not have participated in the pilot study in which we will test the how convincing these messages are

 For both studies, they must not have participated in a previous study in which we originally generated these theme sets

 Current smokers (people who have smoked in the past 30 days)