Comparison of Oral or Intravenous Thiazides vs Tolvaptan in Diuretic Resistant Decompensated Heart Failure

Summary: Broad Objectives: To determine the comparative efficacy of commonly employed strategies to overcome loop diuretic resistance when added to concomitant loop diuretics in hospitalized decompensated heart failure patients with hypervolemia~Specific Aims:~Compare the 48-hour weight change of either intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in decompensated heart failure~Compare the adverse effects of electrolyte depletion and renal function changes between intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure~Pharmacoeconomic analysis of the direct costs of intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure~The investigators will conduct a dual center, randomized, double-blind, double-dummy, parallel design trial comparing: oral metolazone, intravenous chlorothiazide, or oral tolvaptan, in combination with loop diuretics in 60 patients hospitalized for hypervolemic decompensated heart failure and displaying loop diuretic resistance.
Inclusion criteria: inclusion criteria:

 age of 18 years or older

 hospital admission for hypervolemic decompensated heart failure complicated by loop diuretic resistance

 24 hour telemetry monitoring on an inpatient ward

 basic metabolic panel laboratory assessment twice daily during the study period

 Hypervolemia will be diagnosed by the admitting provider as either (i) pulmonary artery catheterization with a pulmonary capillary wedge pressure greater than 19mmHg plus a systemic physical exam finding of hypervolemia (peripheral edema, ascites, or pulmonary edema on auscultation) or (ii) in the absence of pulmonary artery catheterization data 2 of the following signs or symptoms: peripheral edema ascites, jugular venous pressure > 10mmHg, or pulmonary edema on chest x-ray.

 Loop diuretic resistance is defined as a provider decision to pursue combination diuretic therapy because of failure to reach provider defined adequate diuresis (can not exceed urine output of 2 L in past 12 hours) despite receipt of an intravenous loop diuretic dose of a furosemide equivalent of at least 240mg/day over at least the past 12 hours (40mg furosemide = 20mg torsemide = 1mg bumetanide).

Exclusion criteria: :

 decision to pursue hemodialysis by a nephrologist

 estimated glomerular filtration rate by the MDRD equation < 15ml/min/m2

 systolic blood pressure < 85mmHg

 pregnancy

 serum potassium < 3.0mEq/L

 serum sodium > 145mEq/L or < 130mEq/L

 severe malnutrition

 advanced liver disease

 inability to perform standing weights

 inability to collect and measure urine with either a foley catheter or urine collection containers

 concomitant therapy with strong CYP3A4 inhibitors/inducers (systemic ketoconazole, clarithromycin, itraconazole, telithromycin, saquinavir, nelfinavir, ritonavir, nefazodone, rifampin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, St. John's Wort)

 concomitant therapy with p-glycoprotein inhibitors (cyclosporine, erythromycin, tacrolimus, dronedarone, quinidine, or verapamil)

 non-study diuretics (spironolactone doses >75mg/day, eplerenone > 75mg/day, non-study thiazides or loop diuretics, or systemic acetazolamide, triamterene, or amiloride therapy)

 thiazides administration in the previous 24 hours prior to randomization


Enteral Feeding in the Post-Injury Open Abdomen

Summary: The purpose of this study is to determine if Enteral Feeding (EN) in patients with a traumatic bowel injury requiring an open abdomen impacts outcomes. Patients who receive EN will be compared to those who remain nil-per-os (NPO). Additionally, an internal study control will be performed by analyzing concurrent injured patients requiring an open abdomen who did not have a bowel injury.~Specific aims:~Hypothesis 1: EN in patients with a traumatic bowel injury requiring an open abdomen improves fascial closure rate compared to patients who remain NPO.~Hypothesis 2: EN in patients with a traumatic bowel injury requiring an open abdomen reduces infectious complications compared to patients who remain NPO.~Hypothesis 3: EN in patients with a traumatic bowel injury requiring an open abdomen have a lower mortality rate compared to patients who remain NPO.
Inclusion criteria: inclusion criteria:

 All patients with a post-injury open abdomen

Exclusion criteria: :

 Patients to be excluded from analysis include deaths within 24 hours, identification of injury > 24 hours, and those transferred from an outside hospital > 24 hours following initial injury.


The Short-term Effect of ELTGOL on Pulmonary Ventilation Valued Through Electrical Impedance Tomography in Cystic Fibrosis Patients

Summary: Cystic Fibrosis (CF) is the most common lethal autosomal recessive disease. Respiratory therapy is always recommended to the CF patient with pulmonary involvement and has differents techniques and devices, however, there is no consensus on the effectiveness of the techniques used, there is a need to determine the applicability of the therapeutic resources used. Therefore, the aim of the study is to determine the short-term effectiveness of ELTGOL on Average Electrical Impedance on the End of Expiration (MIEFE) pulmonary, assessed by Electrical Impedance Tomography (EIT) in individuals with CF through a clinical trial randomized crossover. Volunteers will be included with FC with moderate to severe lung disease with chest ≥ 74 cm that do not show: episode of pulmonary infectious exacerbations in the last four weeks or during the study period; cor pulmonale; facial deformity that causes air leakage; facial trauma and recent face or esophagus surgery; chest pain; hemoptysis in the last week; continued use of supplemental oxygen (> 8 hours / day); hemoptysis; hemodynamic instability and do not understand the use and command of the techniques used. The sample is selected by convenience from the database of individuals assisted data in Integrative Medicine Institute Professor Fernando Figueira (IMIP). The research will be developed in three phases, divided into three days with an interval of at least 48 hours between phases. The first day will undergo initial assessment and in the days following the intervention by day, ELTGOL or Acapella, in a randomized order.
Inclusion criteria: inclusion criteria: Volunteers with Cystic Fibrosis and lung disease with chest hemiperímetro ≥ 37 cm.
Exclusion criteria: : Episode of pulmonary infectious exacerbations in the last four weeks or during the study period; cor pulmonale; facial deformity that causes air leakage; facial trauma and recent face or esophagus surgery; chest pain; hemoptysis in the last week; continued use of supplemental oxygen (> 8 hours / day); hemoptysis; hemodynamic instability and do not understand the use and command of the techniques used.


Predictive Questionnaires for Risk of Acute COPD (Chronic Obstructive Pulmonary Disease) Exacerbations

Summary: COPD patients frequently suffer intermittent exacerbations of their disease characterised by acute deterioration of symptoms. Acute exacerbations of COPD (AECOPD) are associated with significant impairment of health status, use of health care resources, poor prognosis and increased mortality. The development of simple and practical predictive tools would help to identify COPD patients at greater risk of suffering exacerbations, which is important since those patients would need more intense and early treatment.~This one-year prospective cohort non-drug study will evaluate several COPD-specific questionnaires as predictive tools and the presence of cardiovascular comorbidities as risk factors, for the composite events in study cohorts. The trial duration consists of a screening period (4-6 weeks) and a follow-up period (12 months), 4 visits in total along the study.
Inclusion criteria: inclusion criteria:

 Signed informed consent

 Age ≥ 40 years

 Patients fulfilling criteria for COPD according to the Global initiative for chronic obstructive pulmonary disease (GOLD) stage I or higher

 Smokers or ex-smokers of at least 10 pack-years

 Patients suffering an AECOPD either:

 Admitted to hospital due to AECOPD (severe exacerbation) or

 Confirmed AECOPD at GP (general practitioner) setting (moderate exacerbation) Definition AECOPD: Increase in respiratory symptoms requiring treatment with oral corticosteroids, antibiotics or both.

Exclusion criteria: :

 Patients who have never smoked

 Patients with active long-term respiratory disease (e.g. bronchial asthma, cystic fibrosis, severe bronchiectasis, malignancy, restrictive lung diseases etc.)

 Exacerbation of COPD due to other causes such as pneumothorax and acute decompensated congestive heart failure

 Difficulties in communication (cognitive deterioration, sensorial disability, language barriers)

 Severe disease with poor vital prognosis (life length expectancy less than one year)


Age-adjusted D-dimer Cut-off to Rule Out Pulmonary Embolism in the Emergency Department : A Real Life Impact Study

Summary: A multicentre multinational prospective management outcome study has recently proven the safety of a diagnostic strategy combining clinical probability assessment with an age-adjusted D-dimer cut-off, defined as a value of (age x 10) in patients > 50 years, for ruling out PE in outpatients, with a very low likelihood of subsequent symptomatic VTE. Moreover, this study showed that such a strategy increased the diagnostic yield of D-dimers, as it allowed ruling out PE without further investigation in a significantly higher proportion of patients than when using standard cut-off, particularly so in patients 75 years or older.~The objective of the present study is to confirm in a prospective cohort of real life patients the usefulness of the age-adjusted D-dimer cut-off to rule out PE in patients presenting to the emergency department with suspected PE.
Inclusion criteria: inclusion criteria:

 Consecutive out patients with suspected PE in whom PE has been considered ruled out by negative D-dimers using an age-adjusted cut-off.

Exclusion criteria: :

 Life expectancy less than 3 months.

 Geographic inaccessibility for follow-up.

 Therapeutic anticoagulation for any indication.

 Pregnancy.

 Age less than 18.


A Study of Pre-Operative Treatment of Newly-Diagnosed, Surgically-Resectable Osteosarcoma With Doxorubicin, Ifosfamide, Etoposide, and Cisplatin With Early Metabolic Assessment of Response

Summary: This is a pilot study that will allow investigators to collect data related to early and potentially more accurate response assessments using a chemotherapy protocol that eliminates methotrexate to maximize the dose intensity of doxorubicin. The pilot data will be used to seek funding to more fully address the hypotheses in a multi-institutional, Phase II or Phase III trial. The primary and secondary objectives are as follows:~Primary:~To evaluate the feasibility and potential usefulness of measuring early changes in tumor metabolic activity, assessed by Fludeoxyglucose-Positron Emission Tomography (FDG-PET) imaging and alkaline phosphatase activity, as early predictors of histological response rate at 12 weeks in osteosarcoma patients.~To explore whether histological response can be assessed by a computer algorithm using virtual microscopic images of pathology material, and whether quantifying necrosis in this way correlates with microscope slide-based review.~Secondary:~1. To gather pilot data on the histological response rate, 3-year event-free survival, and toxicity when children and young adults with resectable osteosarcoma are treated using a chemotherapy regimen of alternating courses of doxorubicin/cisplatin (DC) and doxorubicin/ifosfamide/etoposide (IDE).~All patients will receive 4 courses of preoperative chemotherapy courses. With the exception of high-dose methotrexate, which is given weekly, preoperative and postoperative chemotherapy courses are planned to begin every 21 days.~Patients with good histological response (those patients with > 90% tumor necrosis at time of definitive resection) will receive three postoperative chemotherapy courses. The 1st will consist of doxorubicin, dexrazoxane, cisplatin and Granulocyte-Colony Stimulating Factor (G-CSF)(or Polyethylene Glycol filgrastim). The 2nd course will consist of doxorubicin, dexrazoxane, ifosfamide, MESNA, etoposide, G-CSF (or PEG-filgrastim). The 3rd course will consist of ifosfamide, MESNA, etoposide, G-CSF (or PEG-filgrastrim). The total doxorubicin dose will be 450 mg/m2.~Patients with poor response (those patients with < 90% tumor necrosis found on pathology at time of definitive resection) will receive five postoperative chemotherapy courses. High Dose-Methotrexate will be administered during the 1st and 3rd postoperative chemotherapy courses as 4-weekly and 2-weekly doses, respectively. The 2nd course will consist of doxorubicin, dexrazoxane, cisplatin and G-CSF (or PEG-filgrastim). The 4th course will consist of doxorubicin, dexrazoxane, ifosfamide, Mesna, etoposide, G-CSF (or PEG-filgrastim). The 5th cycle will consist of ifosfamide, Mesna, etoposide, G-CSF (or PEG-filgrastrim). The total doxorubicin dose will be 450 mg/m2.
Inclusion criteria: inclusion criteria:

 Must be between 2 and 35 years of age at time of diagnosis

 Must have biopsy-proven, high-grade osteosarcoma.

 Patients with metastases are eligible as long as the lung is the only site of metastatic disease.

 The primary tumor and all pulmonary metastases must be deemed to be potentially resectable. There must be a commitment by the surgical team to resect the primary tumor at week 12, and pulmonary nodules at any point, unless the clinical situation indicates these interventions are not in the patient's best interest.

 Patients must have normal laboratory values and cardiac function as defined below:

 Creatinine clearance or radioisotope GFR of > or equal to 70ml/min/1.73 m2 OR

 A serum creatinine based on age/gender as follows:

 Age Maximum Serum Creatinine (mg/dL) Male Female

 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5

 to < 2 years 0.6 0.6

 to < 6 years 0.8 0.8

 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

 or equal to 16 years 1.7 1.4

 Cardiac: Adequate cardiac function is defined as:

 Shortening fraction of > or equal to 28% by echocardiogram OR Ejection fraction of > or equal to 50% by radionuclide angiogram

 Hepatic: Adequate liver function is described as:

 Total bilirubin of < or equal to 1.5 x upper limit of normal (ULN) for age

 Hematologic function: adequate hematologic function is defined as:

 ANC > or equal to 1.5 x 10^9/L and platelet count > or equal to 100 x 10^9/L

 Female patients must have a negative pregnancy test

 Female patients who are lactating must agree to stop breast-feeding.

 Patients must not be known to be HIV positive. Testing for HIV is not mandatory.

 Sexually active patients of childbearing potential must agree to use effective contraception.

 Patients must be able to cooperate fully with all planned protocol therapy.

 Signed informed consent MUST be obtained from patient or parent/legal guardian prior to any study procedures and study entry.

Exclusion criteria: :

 Patients with any low-grade osteosarcoma, post-radiation osteosarcoma, and osteosarcoma associated with Paget's disease are not eligible.

 Patients with metastases other than lung metastases are not eligible.

 Patients may not have received prior chemotherapy.

['Dexrazoxane', 'Doxorubicin', 'Cisplatin', 'G-CSF', 'PEG-filgrastim', 'Etoposide', 'Ifosfamide', 'Mesna', 'Leucovorin']

Dexrazoxane Doxorubicin Cisplatin G-CSF PEG-filgrastim Etoposide Ifosfamide Mesna Leucovorin


Causes, Characteristics and Mechanisms of Infective Exacerbations in Subjects With Asthma and Chronic Obstructive Pulmonary Disease (COPD)

Summary: Diseases of the airways (bronchi) of the lungs include asthma and chronic obstructive pulmonary disease (COPD), which are leading causes of reduced quality of life, loss of work, hospital admissions and deaths and result in a major economic burden to the patient and society. Worsening (exacerbation) of these conditions is common and is frequently due to viral or bacterial infection, which causes inflammation in the bronchi, i.e. bronchitis. Ways to objectively measure the inflammation are needed to improve diagnosis, cause and severity and to guide treatment. The investigators also need to understand changes in the body's defense (immune) mechanisms that make some patients have more frequent infective bronchitis.~At present, sputum cell counts are able to identify different types of bronchitis, their severity and may be able to differentiate viral from bacterial infection. Other measurements in sputum, exhaled breath, blood and urine are also available to measure this inflammation. Measurement of immune cells in the blood gives us an idea about the working capacity of the immune system of the body.~The investigators plan to study patients with asthma or COPD at the time of worsening of their condition to identify,~To what extent viral or bacterial bronchitis can be diagnosed from tests of inflammation?~How clearing of infection relates to clearing of inflammation?~What are the changes in the body's defense mechanisms that make a patient more prone to frequent infective bronchitis?~How do the measurements in sputum, exhaled breath, blood and urine relate to viral and bacterial bronchitis?~What are the differences in the measurements in sputum, exhaled breath, blood and urine in asthma and COPD?
Inclusion criteria: inclusion criteria:

 Male or female (medically or surgically postmenopausal or practicing an accepted form of barrier or hormonal contraception) subjects between 18 - 80 years.

 Any severity of exacerbation of obstructive airway disease attending the outpatient clinic.

 History of at least two exacerbations in the past 12 months prior to recruitment that required a course of prednisone or antibiotic or long acting bronchodilator or inhaled corticosteroid, in addition to the daily maintenance therapy.

 Signed written informed consent to participate in the protocol and ability to return to the outpatient clinic for repeated clinic visits.

Exclusion criteria: :

 If the exacerbation is severe enough to warrant hospitalization.

 Active malignancy.

 Significant gastrointestinal, hematological, cardiovascular or cerebrovascular disorder that would affect compliance with follow up visits.

 Recent (within the past 2 months) or planned (within the study period) lung surgery.

 Psychosis, alcoholism, active substance abuse or any personality disorder that would make compliance with the follow up visits problematic.

 Pregnant or nursing females, as this could affect the compliance during the trial.

 Any other medical or social condition, which in the opinion of the investigator could confound the interpretation of the data derived from this study.


Evaluation of Breastfeeding Support After Short Time Hospitalization

Summary: The purpose of this study is to evaluate if the developed theory and evidence based programme has a positive effect on mother's breastfeeding self efficacy, establishing an effective breastfeeding and breastfeeding duration after short time hospitalization.
Inclusion criteria: inclusion criteria:

 pregnant women (gestational week 35-36)

Exclusion criteria: :

 women with known physical, psychological and/or social illness/problem that result in hospitalization more than 50 hours after delivery

 women with known pregnancy related illness that result in hospitalization more than 50 hours after delivery

 Women not understanding or speaking Danish

 women expecting multiple babies

 women having decided not to breastfeed

 women expecting to deliver at another hospital than the one she has been visiting during pregnancy

['New Breastfeeding Counselling', 'Treatment as usual']

New Breastfeeding Counselling
Treatment as usual


The Effects of Aging and Estrogen on the Pituitary

Summary: The purpose of this study is to study the effects of aging and estrogen on the brain. Specifically, this study will examine how the hypothalamus signals the pituitary gland to secrete reproductive hormones and how that changes with aging.
Inclusion criteria: inclusion criteria:

 45-55 or 70-80 years old

 History of natural menopause defined by the absence of menses for at least 12 months (or history of surgical menopause defined as bilateral oophorectomy) and a FSH level >26 IU/L

 On no hormonal medication or herbal supplements and/or over the counter menopause therapy for a minimum of 2 months prior to study

 Normal thyroid stimulating hormone, prolactin, factor V Leiden, and complete blood count - Normal blood urea nitrogen and creatinine (< 2 times the upper limit of normal)

 basal metabolic index ≤ 30

 Non-smokers or smoke less than 10 cigarettes/day

Exclusion criteria: :

 Absolute contraindications to the use of physiologic replacement doses of estrogen, including a negative screening mammogram within the past 24 months

 History of coronary artery disease

 On medications thought to act centrally on the GnRH pulse generator

 Past history of hypersensitivity or allergy to narcotics, vancomycin, muscle relaxants, aspirin, and/or anaphylactic reaction(s) to other drugs

 Prior history of breast cancer and/or blood clots

['GnRH', 'NAL-GLU GnRH antagonist', 'Estrogen patch']

GnRH
NAL-GLU GnRH antagonist
Estrogen patch


VERITAS: An Evaluation of the Veniti Vidi Retrievable Inferior Vena Cava Filter System in Patients at Risk for Pulmonary Embolism

Summary: This is a prospective, multicenter single arm, nonrandomized study that will include 150 patients at a maximum of 20 investigational sites. It is estimated that it may take 13 months to complete enrollment. Follow-up will continue through 24 months post-implant or one month post-retrieval, whichever occurs first. It is required that filters be retrieved from at least 50 patients and the filter is permanent in at least 50 patients.
Inclusion criteria: inclusion criteria:

 ≥ 18 years

 Investigator judges caval filtration clinically indicated for prevention of pulmonary embolism in patient with venous thromboembolic disease or at high risk for venous thromboembolic disease. Patient must meet at least one of the following:

 Anticoagulant therapy is contraindicated, has failed, cannot be achieved or maintained, must be interrupted, resulted in complication, or places the patient at high risk of complication and the patient has:

 Pulmonary embolus

 Iliocaval deep vein thrombosis (DVT)

 Severe trauma with high risk of venous thromboembolism including closed head injury, spinal cord injury, or multiple long bone or pelvic fractures

 Surgery planned with high risk of venous thromboembolism including procedures such as bariatric, orthopedic, or pelvic surgery

 Past history of thromboembolic disease undergoing surgery

 Therapeutic anticoagulation can be achieved, but the patient has:

 Venous thromboembolism such as pulmonary embolism or DVT with limited cardiopulmonary reserve

 Massive pulmonary embolism already treated with thrombectomy or any thrombolytic therapy

 Chronic pulmonary embolism already treated with thrombectomy

 Large, free floating proximal, e.g., iliofemoral or iliocaval, DVT

 Iliocaval DVT with planned catheter thrombectomy or thrombolysis treatment OR

 Medical condition with high risk of venous thromboembolism

Exclusion criteria: :

 Condition that inhibits radiographic visualization of the IVC

 Known inadequate venous anatomy to allow insertion or retrieval of the filter from the IVC including occlusion of the SVC or jugular veins

 Known IVC transverse diameter at target implant site > 28 mm

 Known obstructing abdominal mass or anatomy that is not suitable for infra-renal placement of IVC filter

 Known duplication of IVC or left-sided IVC

 Severe kyphosis or scoliosis

 Known IVC thrombosis extending to renal veins, or renal or gonadal vein thrombosis

 Risk for septic pulmonary embolism

 Confirmed bacteremia

 Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min, or dialysis dependent.

 Contrast agent allergy that cannot be adequately pre-medicated

 Known hypersensitivity to Nitinol (nickel-titanium), platinum, Polyether ether ketone (PEEK), UV Cure Adhesive or Cyanoacrylate Adhesive

 Uncontrolled or active coagulopathy or known uncorrectable bleeding diathesis

 Life expectance < 6 months

 Female of childbearing potential who is pregnant or plans to become pregnant during the duration of the clinical study. (If a female of child bearing potential wishes to participate, she must have negative pregnancy test within 48 hours of the implantation and any retrieval procedures.)

 Has filter in place or underwent filter retrieval in previous 60 days

 Simultaneously participating in another therapeutic drug or device clinical trial or has participated in such trial in the 30 days prior to enrollment

 Investigator considers patient to be a poor candidate for the study or that including the patient may compromise the study, e.g., suspect patient may not comply with follow up procedures, concomitant conditions

 Patient does not wish to consent to study or comply with study procedures, including possible 2 year follow up

['Deep Vein Thrombosis', 'Pulmonary Embolus']


Intelligent Intensive Care Unit

Summary: Delirium, as a common complication of hospitalization, poses significant health problems in hospitalized patients. Though about a third of delirium cases can benefit from intervention, detecting and predicting delirium is still very limited in practice. A common characterization of delirium is change in activity level, causing patients to become hyperactive or hypoactive which is manifested in facial expressions and total body movements. This pilot study is designed to test the feasibility of a delirium detection system using movement data obtained from 3-axis wearable accelerometers and commercially available camera with facial recognition video system in conjunction with electronics medical record (EMR) data to analyze the relation of whole-body movement and facial expressions with delirium.
Inclusion criteria: inclusion criteria (ICU Patients):

 Intensive care unit patient

 18 years of age or older

Exclusion criteria:  (ICU Patients):

 Anticipated intensive care unit stay less than one day

 Less than 18 years of age

 Inability to wear a motion sensor watch (ActiGraph)

 inclusion criteria (Healthy Controls):

 18 years of age or older.

 sleeps in home environment

['Confusion Assessment Method', 'Accelerometer', 'Commercially available camera', 'Internet Pod (iPod)', 'Cortisol Swab']

Confusion Assessment Method
Accelerometer
Commercially available camera
Internet Pod (iPod)
Cortisol Swab


Multidimensional Assessment of Fatigue in Multiple Sclerosis- Observational Study - Ticino

Summary: Fatigue is a common symptom in patients with multiple sclerosis, however, its nature is not completely understood. Fatigue overlaps often with other symptoms such as somnolence, depression and cognitive disorders, from which it is not always readily distinguished. The evaluation of fatigue and the three most frequently associated symptoms using a multidimensional approach might allow to understand, which methodology is the best indicated to estimate the prevalence of fatigue with greatest accuracy, leading to a better differentiation of the symptoms in the diagnostic setting.
Inclusion criteria: inclusion criteria:

 Definite diagnosis of MS (14,15) or CIS (16);according to the most recent standard criteria

 Expanded Disability Status Scale (EDSS) score < 7.0 (17);

 Last magnetic resonance imaging (MRI) within the previous 12 months;

 Male or female;

 >18 years old;

 Willing to perform the study procedures;

 Signed Informed consent.

Exclusion criteria: :

 Mini Mental Status Examination (MMSE) score < 24;

 Relapse within the last 3 months;

 Radiologically isolated syndrome (RIS);

 History of drug and/or alcohol abuse;

 Any serious general medical condition like decompensated cardiopulmonary disease, cancer or decompensated renal failure, as well as any neurological condition (other than MS) that can interfere with the correct execution of the study design.


3 Months' Versus 6 Months' Anticoagulation in Patients With DVT and/or PE

Summary: To determine whether 3 months' anticoagulation is as good as or better than 6 months' for the treatment of DVT/PE
Inclusion criteria: inclusion criteria:

 Patients aged 18 years or more with suspected or proven DVT/PE whom the clinician intended to anticoagulate.

Exclusion criteria: :

 DVT/PE severe enough to require thrombolysis or pulmonary embolectomy.

 DVT/PE in the preceding 3 years.

 Neoplasia diagnosed/treated within previous 3 years.

 Pregnancy.

 Known major thrombophilias.

 Prolonged or continuous immobility or confinement to bed.

 Previous allergy to heparin or warfarin.

 Requirement for long-term anticoagulation.

 Inability to give informed consent.

['Duration of anticoagulation', 'Warfarin duration']

Duration of anticoagulation
Warfarin duration

['Deep Vein Thrombosis', 'Pulmonary Embolism', 'Deep Vein Thrombosis With Pulmonary Embolism']


Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)

Summary: Systemic lupus erythematosus (SLE) is an independent risk factor for atherosclerosis. Endothelial dysfunction is the earliest marker of atherosclerosis and is measured by flow mediated dilation (FMD) of the brachial artery. The purpose of the study was to measure FMD in mild, stable SLE patients and look for change in FMD with the immunosuppressant drug mycophenolate mofetil (MMF).
Inclusion criteria: inclusion criteria:

 Female SLE patients

 Age 18-60 years

 If premenopausal using a reliable method of contraception

 Clinically stable disease

 Taking hydroxychloroquine and up to 15mgs of prednisolone daily

Exclusion criteria: :

 Smokers

 Pregnancy or breast feeding

 Use of other immunosuppressants (hydroxychloroquine and stable dose of prednisolone up to 15 mgs daily will be permitted)

 Use of any investigational drug within 1 month prior to screening

 Acute infections 2 weeks prior to Visit 1

 History of ischaemic heart disease or end stage renal disease

 Current signs or symptoms of severe, progressive or uncontrolled hepatic, haematological, gastroenterological, endocrine, pulmonary, cardiac or neurological disease

['Systemic Lupus Erythematosus', 'Atherosclerosis']

Systemic Lupus Erythematosus
Atherosclerosis


High Dose Ribavirin in the Treatment of Chronic Hepatitis C

Summary: Treatment of patients with chronic hepatitis C infected with genotype 1 hepatitis C virus (HCV) consists of combined peginterferon/ribavirin for 48 weeks. Approximately 50% of patients experience sustained virological response which equals cure. All other patients either do not respond or experience recurrence of HCV virus and chronic hepatitis. Important predictors of successful treatment are sustained dosing of both peginterferon and ribavirin. With regard to the latter, clinical evidence indicates that higher ribavirin doses may in fact even improve treatment outcome. However, high ribavirin doses cause hemolytic anemia which require dose reductions. Recent clinical experience show that erythropoetic growth factors, including erythropoetin, can counteract hemolytic anemia caused by antiviral treatment in chronic hepatitis C patients. Therefore, the current trial aims to test whether higher ribavirin doses adapted to a target plasma concentrations instead of a weight-based dosing result in better healing rates, and whether ribavirin-associated hemolytic anemia can be compensated by concommitant erythropoetin treatment.~Using a randomized, controlled, open-label design, the investigators hypothesize that patients with high ribavirin doses adapted to plasma levels experience better viral clearance than patients treated with standard weight-based ribavirin doses. In addition, the investigators hypothesize that erythropoetin treatment will counteract hemolytic anemia induced by ribavirin thereby allowing maintenance of target plasma concentrations without ribavirin dose reductions.
Inclusion criteria: inclusion criteria:

 Male and female patients aged 18-65 years

 Elevated liver enzymes levels

 Compensated liver disease

 Available liver histology confirming METAVIR F2 fibrosis

 Written consent to participation

Exclusion criteria:

 Age <18, >65

 Prior ribavirin treatment

 Intolerance towards ribavirin, PegIFN or erythropoetin

 Pregnancy or breast feeding

 Relevant cardiovascular or pulmonary disease

 Kidney insufficiency (creatinine clearance <50ml/min)

 Coinfection with HIV or hepatitis B virus

 Hepatic comorbidities (hemochromatosis, Wilson's disease, autoimmune disorders)

 Alcohol consumption > 40g/day

 Psychiatric disorders

 Malignancy (except for basalioma)

 Active consumption of illicit drugs

 Participation in another trial shorter than 3 months prior to inclusion

 Lack of consent

['High ribavirin dose', 'Standard ribavirin dose']

High ribavirin dose
Standard ribavirin dose


Enhanced Collaborative Depression Treatment in Primary Care: The RESPECT-D-E Trial

Summary: Primary care physicians have emerged as the predominant mental health care providers for diagnosing and treating depression. The majority of patients with mood disorders receive treatment in the primary care setting, within which approximately 10-30% of all patients present with a depressive disorder. Comprehensive 'Collaborative Care' models of depression management significantly improve depression outcomes and health-related quality of life. Core features of these programs include use of a trained depression care manager to closely coordinate with primary care clinicians, support treatment recommendations, provide patient education, conduct patient follow-up to ensure adequate treatment, and manage as-needed access to psychiatrists for patients with more complex presentations. Evidence based Collaborative Care models do not currently weave in the use of web-based or mobile technologies. These technologies offer unique features that may make collaborative depression care more effective. The digital health coaching program for depressive symptoms enhanced during Phase I of the current project is a web-based tool featuring video, text, links and graphics which provide patients with education, self-management techniques, tailored feedback, and tools for tracking treatment progress. The RESPECT-D (Re-engineering Systems of Primary Care Treatment of Depression) intervention is a collaborative depression management model for primary care. The primary objective of this project is to compare the efficacy of an enhanced Collaborative Care model for depression (RESPECT-D-E) to the standard model (RESPECT-D) for patients with minor and major depression and dysthymic disorder. This study will be a randomized controlled trial with 150 participants who are receiving antidepressant medication treatment in the primary care setting. The primary objectives are: reduction in subject reported depressive symptoms, improvement in subject reported health related quality of life and improvement in subject adherence to treatment regimen as demonstrated by self-report measures and clinician-administered assessment. The investigators hypothesize that compared to RESPECT-D at 12 weeks, participants randomized to RESPECT-D-E will demonstrate: a greater reduction in depressive symptoms, a greater improvement in health-related quality of life and a greater satisfaction with quality of depression care received.
Inclusion criteria: inclusion criteria:

 Males and Females, ages 18 and older who are self-reporting generally good health.

 Newly started on an antidepressant medication, switched to a different antidepressant medication or prescribed an increased dosage of antidepressant medication within the past 2 weeks.

 A Hamilton Depression Rating Scale (HAM-D) score of greater than 10.

 A Patient Health Questionnaire (PHQ-9) score of 10 or greater, with endorsement of depressed mood or anhedonia, and endorsement of impaired daily function.

 Meets diagnostic criteria for Major Depressive Disorder, persistent Minor Depressive Disorder (i.e., > 1 month duration), or Dysthymic Disorder via a structured interview with the PRIME-MD.

 Able to read, understand, and sign the Informed Consent in English.

 Willing and able to comply with study requirements.

 Well-versed in using a personal computer and the internet and must have easy access to a computer connected to the internet everyday (both weekdays and weekends).

 Enrollment in Surescripts Pharmacy benefit plan

 Currently under care with a Provider in Family Medicine at Cheshire Medical Center / Dartmouth-Hitchcock Keene

Exclusion criteria: :

 Subjects must not have a major psychiatric co-morbid condition (schizophrenia, bipolar affective disorder, obsessive-compulsive disorder, PTSD, or a depressive disorder with psychotic features, as determined from chart review and patient report).

 Subjects must not have a substance use disorder or dependence as assessed by: CAGE Alcohol Dependence Questionnaire score >3

 Subjects must not have a history of treatment -resistant depression as defined by the following: Psychiatric hospitalization within the past year; More than 2 clinically ineffective antidepressant medication trials, of adequate duration and adequate dose, within the current depressive episode; Any history of Electroconvulsive Therapy (ECT); A trial of Monoamine Oxidase inhibitor (MAO) within the past year.

 Subjects must not report being actively suicidal

 Subjects must score 4 or greater on the Callahan Six-Item Cognitive Screening assessment

 Subjects must not be diagnosed with a terminal or near terminal medical illness such that their primary care provider has estimated the patient has less than 6 months to live.

 Subjects reporting any medical condition that would make it unsafe to participate in a research study.

 Participation in any other clinical research study within the past 30 days.

 Participation in any on-line depression-related coaching or lifestyle improvement program within the past 5 years.

['Depressive Disorder, Major', 'Depressive Disorder, Minor', 'Dysthymic Disorder']

Depressive Disorder
Major
Depressive Disorder
Minor
Dysthymic Disorder


Becaplermin Gel for MARTORELL's Hypertensive Leg Ulcers

Summary: Background: No medical treatment has proved its efficacy for the treatment of hypertensive leg ulcers in a well designed trial.~Primary aim of the study: to compare the rate of healing in hypertensive leg ulcers treated with becaplermin gel (Regranex Gel®) daily application versus the application of the same quantity of an hydrogel (Duoderm Hydrogel™), corresponding to the excipient of becaplermin gel.~Method: Ambulatory or hospitalized patients presenting with an hypertensive leg ulcer, were randomized to receive either a daily application of becaplermin gel or hydrogel during 8 weeks. At week 8, a pinch graft was proposed to patients whom the ulcer has not healed.~Primary aim of the study: Complete closure at week 8~Secondary aims: percentage of wound area reduction at week 8, complete closure at week 12, pain and quality of life during treatment~Study hypothesis: becaplermin gel may promote the healing of hypertensive leg ulcers and be an alternative medical treatment to the skin graft usually proposed
Inclusion criteria: inclusion criteria:

 patients 18 years of age or older, able to give informed consent and to follow the treatment procedure

 target ulcer area between 1 and 30 cm2

 consecutive patients presenting with one or more leg ulcers diagnosed as hypertensive MARTORELL's ulcers

 presence of an arterial hypertension, according to the WHO criteria, treated or not; and/or presence of a diabetes treated by oral agent, insulin or diet

 absence of clinical signs of chronic venous insufficiency: skin hyperpigmentation, lipodermatosclerosis

 absence of significant peripheral arterial occlusive disease: presence of peripheral pulses or ankle brachial index ≥0.8

 absence of clinical sign of arterial insufficiency: intermittent claudication, resting pain

 superficial spreading necrotic ulcer

 presence of spontaneous pain

 presence of a red purpuric margin

Exclusion criteria: :

 pregnancy

 allergy to hydrogel or to becaplermin gel

 uncontrolled or evolving systemic disease: cardiac or renal failure, hepatic insufficiency, malignant disease, thrombotic disease, vasculitis or other connective tissue disorder

 presence of a cryoglobulinemia

 serum creatinine concentration greater than 200µmol/L or uncontrolled diabetes (fasting blood glucose > 2,5 g/L under treatment)

 concomitant treatment by ILOMEDINE

 bone, joint or tendon (except for achilles tendon) exposition in the wound

 systemic treatment with corticosteroid agents or cytotoxic drugs in the past 3 months before inclusion

['becaplermin gel', 'Duoderm Hydrogel™']

["MARTORELL'S ULCER", 'Hypertensive Leg Ulcer', 'Necrotic Angiodermatitis']

MARTORELL'S ULCER
Hypertensive Leg Ulcer
Necrotic Angiodermatitis


Effects of LMWH in Healthy Subjects Treated With TB-402 and Effects of TB-402 in Healthy Subjects Treated With Warfarin

Summary: Administration of LMWH in healthy male subjects treated with TB-402 and administration of TB-402 in healthy male subjects treated with warfarin
Inclusion criteria: inclusion criteria include:

 Males 18 to 45 years of age

 Healthy according to medical history, physical exam, ECG, blood pressure and heart rate, and laboratory profile of blood and urine

Exclusion criteria:  include:

 Self or family history of cardiovascular or pulmonary disorder, or coagulation or bleeding disorders or reasonable suspicion of vascular malformations e.g. cerebral haemorrhage, aneurysm or premature stroke

 History of important bleeding episodes

 Previous allergic reaction to immunoglobulin

 Present or previous history of severe allergy, for example asthma or anaphylactic reactions

 FVIII:C <50% at screening

 Clinically significant out of range values for any coagulation test during screening

 Received prescribed medication, over the counter medication or herbal medicines within 14 days of receipt of TB-402

['LWMH in TB-402 treated subjects or TB-402 in warfarin treated subjects']


Epidemiology of Community Acquired Pneumonia in North Israel

Summary: Pneumonia in general and CAP in particular is considered as one of the most common bacterial infections, associated with high rates of morbidity and mortality and is highly significant economically since all respiratory infections, and pneumonia especially, cause about 80% of antimicrobials use in the community. The high frequency of respiratory infections and the excessive use of antimicrobials are major contributors to the development of pathogens resistant to antimicrobials. In addition, in CAP almost all patients are treated empirically, without identification of causing pathogen.~Aim of study: To identify common pathogens causing CAP in hospitalized patients in north Israel.
Inclusion criteria: inclusion criteria:

 Community acquired pneumonia

 Hospitalization

Exclusion criteria: :

 Immunocompromised patients

 Patients under chemotherapy treatment

 Patients under steroids treament


Equivalency Study of Two Formulations of Mometasone Furoate Nasal Spray (Study P04419)

Summary: This is a multicenter, open-label, randomized, parallel group comparison study to verify the clinical equivalency of the old formulation (50 mcg as mometasone furoate [MF] in 50 μL of solution per spray) to the new formulation (50 mcg as MF in 100 μL of solution per spray) in patients with perennial allergic rhinitis.
Inclusion criteria: inclusion criteria:

 Patients of mongoloid race residing in Japan who satisfy all of the following criteria:

 Patients having symptoms of perennial allergic rhinitis of moderate or severe degree, according to the classification of severity in the guidelines for the treatment of nasal allergy (partial revision) as well as a score of at least 4 in the score of 4 nasal symptoms, at the time of obtaining informed consent and during the pretreatment observation period.

 Patients with a positive skin reaction test or specific IgE antibody quantitation, and with a positive cytological examination of nasal discharge (eosinophils) or nasal challenge test.

 Outpatients who are at least 16 years of age at the time of informed consent obtained.

 Male or female.

 Patients who have the ability to give written informed consent (informed consent of the guardian must also be obtained for patients younger than 20 years).

 Patients who can keep nasal allergy diary without fail.

Exclusion criteria: :

 Patients with coexisting tuberculous disease or lower respiratory tract infection, or patients who, at the time of registration, have acute upper respiratory tract infection, acute pharyngitis, acute amygdalitis etc.

 Patients with coexisting infections or systemic mycosis for which there are no effective antibiotics.

 Patients with unhealed nasal septum ulcers, nasal surgery scar, or nasal trauma.

 Patients with a history of hypersensitivity to steroids or mometasone furoate.

 Patients who are pregnant or nursing or who may be pregnant and patients or patients' partners who desire to become pregnant during the study period.

 Patients with severe hepatic, renal, cardiac, hematological disease, diabetes mellitus, hypertension or other serious coexisting diseases and whose general condition is poor.

 Patients also allergic to pollen and the pollen release season occurs during the study period.

 Patients with vasomotor rhinitis or eosinophilic rhinitis.

 Patients with a nasal condition which may interfere with efficacy evaluation of the investigational product.

 Patients who develop disease affecting nasal symptoms during the pretreatment observation period, i.e., during the 7 days before actual registration.

 Patients who are participating or have participated in a clinical trial of another investigational drug within 120 days (4 months) before the day of the informed consent for this study.

 Patients for whom the period of discontinuation of previous treatment effective for allergic rhinitis before the start of the investigational product administration is not sufficient or who cannot avoid its use.

 Patients receiving specific desensitization therapy or nonspecific modulation therapy or who had just discontinued such therapies within 90 days (3 months) before providing consent to this study (unless such therapies are ongoing as maintenance therapy and had been started 180 days [6 months] or more before consent to this study).

 Other patients judged inappropriate for study by the investigator or subinvestigator.

['mometasone furoate', 'mometasone furoate']


Methylphenidate for Depressed Cancer Patients Receiving Palliative Care

Summary: The purpose of this study is to determine whether methylphenidate is an effective treatment for depression and to document the safety and tolerability of methylphenidate in combination with an Selective Serotonin Reuptake Inhibitor (SSRI) in SSRI treated, terminally ill, hospice and palliative care cancer patients. The investigators hypothesize that depressed hospice and palliative care patients will be more likely to have a 50% reduction in scores on a clinical measure of depression after treatment with Methylphenidate plus an SSRI compared to those patients who are taking a placebo plus an SSRI.
Inclusion criteria: inclusion criteria:

 Inclusion:

 Either enrolled in the OHSU radiology/oncology clinic or VA palliative care, and living within 120 miles of the Portland VAMC.

 Life-limiting disease is any type of solid or blood cancer.

 Eighteen years of age or older.

 Life expectancy of 1 year or less as reflected by hospice admission or palliative care status. Although exact life expectancy can not be predicted, actively dying patients with estimated life expectancy of < 10 days are unlikely to be enrolled.

 Diagnosis of major depression disorder as determined by the Structured Clinical Interview for Diagnosis (SCID).

 Significant depressive cognitive symptomatology as determined by a MADRS greater than 19.

 Currently taking an SSRI but still depressed enough to meet eligibility criteria or not taking SSRI but depressed enough to start on SSRI.

 Willing and able to give informed consent to participate in this study as demonstrated by the MacArthur Competence Assessment Tool for clinical research.

 Speaks/understands English.

 For patients at home who cannot self-administer medications, has a caregiver who can assist with administering medication.

Exclusion criteria: :

 Exclusion:

 Dementia or Delirium as determined by the Short Portable Mental Status Questionnaire (SPMSQ) score of less than 7.

 Diagnosis of delirium as determined by the Confusional Assessment Method (CAM).

 Any of the following Brief Psychiatric Rating Scale (BPRS) items rated 4 -, elated mood, suspiciousness, hallucinations, excitement, distractibility or motor hyperactivity.

 Severe insomnia.

 Severe anxiety.

 Significant suicidal ideation.

 History of current mental disorder in which depressive symptoms occur, but for which psychostimulants are contraindicated (schizophrenia and bipolar disorder will be based on history; active psychotic symptoms on selected BPRS items).

 History of stimulant abuse or other active, severe substance abuse.

 Contraindications to methylphenidate or an SSRI including significant cardiac arrhythmias; uncontrolled, severe hypertension; moderate-severe angina; seizure disorder; severe COPD; use of medications such as Levodopa, monoamine oxidase inhibitors, and lithium; diagnosis of narrow-angle glaucoma; or history of SSRI-induced hyponatremia,.

 Physical symptoms including increased blood pressure (DBP greater than 115, SBP greater than 180), pulse greater than 120, irregular pulse, or chest pain consistent with angina.

 Treatment for depression with a non-SSRI antidepressant including Bupropion and Venlafaxine during protocol.

 Known serum creatinine > 3.0, or severe liver disease as reflected by jaundice or hepatic encephalopathy.

 Unable to swallow pills, however if patient has gastrostomy tube or feeding tube in place the study medicines may be administered by this route. Pills may be poured into food.

 Receiving hospice care in a skilled nursing facility.

['Methylphenidate', 'Placebo', 'Selective Serotonin Uptake Inhibitor (SSRI)']

['Depression', 'Palliative Care', 'Cancer', 'Mental Disorder']

Depression
Palliative Care
Cancer
Mental Disorder


Patients With High-risk Acute Coronary Syndrome Without ST-segment Elevation

Summary: This non-inferiority study aims at comparing Versa® to the reference enoxaparin (Clexane®, Sanofi-Aventis) in patients with high-risk unstable angina and NSTEMI. The main justification is the search for scientific evidence to prove the Versa® effectiveness for this new therapeutic indication, since it is a product with potential for reducing costs, with effectiveness and safety comparable to the reference drug.
Inclusion criteria: inclusion criteria:

 ICF signature;

 The research subject must agree about following all instructions and perform the procedures and study visits;

 Men and women over the age of 18 and below the age of 75;

 History of angina of rest with a minimum duration of 20 minutes in the last 24 hours at the beginning and at least for 10 days.

 Patient Randomization up to 6 hours after the arrival at the emergency sector.

 Evidence of NSTEMI or unstable angina due to one or more of the following criteria:

 1. Dynamic alterations on the T-wave (ST-segment depression or elevation > 1 mm, and/or T-wave inversions which are solved at least partially when the symptoms are relieved) or 2. Unevenly ST-segment (depression or elevation) in a transitional way under continuous derivations (V1+V2 or V3+V4 or V5+V6 or D1+AVL or D2+D3+AVF) or 3. Biochemical alteration on the myocardial necrosis markers (CKMB mass, troponin T or I and CPK), with the appearance of enzymatic curve, characterizing myocardial injury or 5. Pulmonary Edema; or 6. Angina associated to murmur of mitral regurgitation; or 7. Angina with heart sound to cardiac auscultation or throes; or 8. Angina with hypotension;

Exclusion criteria: :

 12-derivation-ECG with persistent ST-segment elevation;

 Diagnosis of angina by secondary cause (e.g., anemia, fever, hypovolemia, dehydration, use of cocaine);

 Use of non-fractionated heparin or low-molecular weight heparin in the prior 48 to the randomization;

 Concomitant diseases, such as severe renal failure (creatinine clearance lower than 30ml/min.) and hepatic, or other significant comorbidities under investigator judgment;

 Recent hemorrhagic cerebrovascular accident (last 12 months);

 Patient scheduled for cardiac surgery of myocardial revascularization;

 Use of drugs, alcohol abuse;

 Pregnancy or lactation;

 Recent neurosurgery or ophthalmic surgery (last 3 months);

 History or diagnosis of coagulopathy;

 Medical record containing allergy, hypersensibility or intolerance to any of the drug components to be used on this study, which is judged as clinically significant in the main investigator's opinion;

 Recent participation (last 12 months) in a clinical study.

['Non ST Segment Elevation Myocardial Infarction', 'Unstable Angina']


To Assess the Efficacy and Safety of Adalimumab in Subjects With Moderate to Severe Hidradenitis Suppurativa

Summary: The trial is a 12-week phase 2 study. Subjects will be given subcutaneous injections at weeks 0 (160mg), 2 (80mg), and then every other week (40mg) until week 12 in subjects with moderate to severe hidradenitis suppurativa.
Inclusion criteria: inclusion criteria:

 Subjects with moderate to severe HS as defined by a HSSI > 8 AND at least ONE of the following:

 HS >1 year duration with multiple ER or doctors visits related to HS

 Intralesional kenalog injection >5/year, however none within 2 weeks of entry

 Failed systemic retinoids, but not within 3 months of entry

 Failed at least one prior course of antibiotic therapy, which must not have been administered within 2 weeks of entry to the study (excluding the recommended antibiotic regimen given for evidence of active infection immediately before enrollment)

 History of surgery (reconstructive), but not within 3 months of entry

Exclusion criteria: :

 Women who are pregnant, nursing, or planning pregnancy within 6 months after the last injection (this includes father's who plan on fathering a child within 6 months after their last injection).

 Use of other systemic anti-inflammatory medication except NSAIDs and low dose systemic steroids (equal or less than 10 mg daily prednisolone or equivalent).

 If found to have an active infection, patients must have completed topical or oral antibiotic therapy at least 7 days before first injection.

 Have a known history of serious infections (e.g., hepatitis, pneumonia or pyelonephritis) in the previous 3 months.

 Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.

 Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (e.g., nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly.

 Have a concomitant diagnosis or history of congestive heart failure.

 Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.


The Study of Drotrecogin Alfa (Activated) in a Subpopulation of Adult Patients With Severe Sepsis

Summary: Severe sepsis is defined as a systemic inflammatory response syndrome that results from infection and is associated with acute organ dysfunction. It usually results from bacterial infections, but it may occur in response to other pathogens, such as fungi, viruses, and parasites.
Inclusion criteria: inclusion criteria:

 Adult patients with severe sepsis.

 Presence of a suspected or proven infection.

 One or more sepsis-associated organ failure.

Exclusion criteria: :

 Are indicated for the treatment with drotrecogin alfa (activated) in the investigative site country.

 Are contraindicated for treatment with drotrecogin alfa (activated) under the applicable label in the investigative site country.

 Platelet count <30,000/mm3.

 Are receiving therapeutic heparin.


Mometasone Furoate on Sleep Disturbances in Subjects With Seasonal Allergic Rhinitis (Study P04608) (COMPLETED)

Summary: This study will hope to show that by relieving the participant's nasal symptoms of seasonal allergies using mometasone furoate nasal spray, the participant will obtain a better quality of night-time sleep, which in turn, causes less daytime sleepiness so that he/she can function productively during the day.
Inclusion criteria: inclusion criteria:

 Must be >=18 years of age and older, of either sex, and of any race.

 Clinically symptomatic at Screening (Day -7 to -4)and at Baseline (Day 1)

 At Screening Visit, must have complaints of sleep disturbance while symptomatic with seasonal allergic rhinitis (SAR) and must have a score of 30 or greater for the Sleep Disturbance Sleep Scale (items 1,3,7 and 8)

 At the Baseline Visit, must have complaints of sleep disturbance and daytime somnolence while symptomatic with SAR and with a score of 30 or greater for the Sleep Problems Index II (SLP9) and 30 or greater for the Daytime Somnolence Sleep Scale (items 6, 9, and 11)

 Must have a 2-year or longer history of SAR occurring during the same season as the current study.

 Must have skin tests positive for outdoor allergens common in subjects with SAR prevalent during the time of this study, such as, trees, grasses, weeds, ragweed, and molds. The skin tests should be performed at Screening if not done within 12 months prior to the Screening Visit

 Must be free of clinically significant disease that would interfere with study evaluations

 Women of childbearing potential need to use a medically accepted method of birth control prior to Screening and during the study, or provide documentation of surgical sterilization. Women who are not sexually active at enrollment must consent to the use of a medically accepted method of birth control if/when they become sexually active during study participation.

 Female subjects of childbearing potential must have a negative urine pregnancy test at the time of enrollment at the Baseline Visit.

Exclusion criteria: :

 Women who are pregnant, intend to become pregnant during the study, or are nursing

 Evidence of nasal polyps, deviated septum, or other intranasal anatomical obstruction(s) that would interfere with nasal airflow

 Acute or chronic sinusitis being treated with antibiotics and/or topical or oral nasal decongestants

 Acute respiratory infection within 2 weeks of the Screening Visit

 Diagnosis of clinically relevant sleep problems unassociated with allergies

 Complaints (within 12 months of the Screening Visit to their health-care provider) of difficulty sleeping or daytime sleepiness while not experiencing SAR symptoms, and continue with these complaints

 Snoring associated with an enlarged uvula or other upper airway pathology

 Had episodes of snoring associated with gasping or choking

 Awakened suddenly, on more than 1 occasion during the month preceding the Screening Visit, with a gasping or choking feeling

 Requires the use of oral appliances at night for bruxism (teeth gnashing) or temporomandibular joint problems

 Diagnosis of asthma with daytime and nighttime asthma symptoms not controlled by short-acting beta-2 adrenoceptor agonists

 Dependence on nasal, oral or ocular decongestants, nasal topical antihistamines, or nasal steroids.

 Currently undergoing a progressive course of immunotherapy (hyposensitization). Subjects on a regular maintenance schedule prior to the Screening Visit and who wish to remain on this schedule during the study are eligible for study inclusion; however, they may not receive hyposensitization treatment within 24 hours prior to any study visit

 Smokers or ex-smokers who have smoked within the previous 6 months

 Concomitant medical problem that may interfere with participation in the study, eg, repeated migraine episodes, uncontrolled convulsive disorders.

 Any of the following clinical conditions: Active or quiescent tuberculosis infection of the respiratory tract, untreated fungal, bacterial, systemic viral infections or ocular herpes simplex.

 Subjects participating in any other clinical study(ies).

 Subjects allergic to or with a sensitivity to the study drug or its excipients.

 Subjects who are night-shift workers or do not have a standard asleep at night/awake during the day cycle

['Mometasone Furoate Nasal Spray (MFNS)', 'Placebo']

Mometasone Furoate Nasal Spray (MFNS)
Placebo


Effects of Remote Ischemic Preconditioning on Moderate PVD Patients A Pilot Randomized Control Trial

Summary: Remote ischemic Preconditioning (RIPC) is a phenomena first observed in cardio-thoracic patients in which exposing the limbs for periods of short intermittent ischemia produces protective effect on heart muscle. The concept was applied to many other parts of the body and the results are positive so far.~No human trials on this concept has been conducted in patients with peripheral vascular disease so far but applying the concept for healthy individuals shows vessels dilatation and animal trials shows degree of new vessels formation in addition to reports of symptoms improvement.~The trial candidates will be allocated blindly in 4 groups. All groups will have advice about exercise which is the standard practice now. The first group will have supervised exercise. The second group will in addition to the supervised exercise get the ischemic preconditioning with the blood pressure cuff. The third group will get the ischemic preconditioning and the fourth group will get the standard exercise advice. All candidates will have Magnetic Resonance Image Scan (MRA) for their blood vessels in the beginning of the trial and again at the end.~The effect of the RIPC (Remote ischemic Preconditioning) and exercises on patient symptoms, new vessel formation and other parameters will be recorded
Inclusion criteria: inclusion criteria:

 Known moderate PVD

 New claudication patient with Rutherford stage 2 and Fontaine stage 2a symptoms

Exclusion criteria: :

 Known upper limb PVD

 Severe cardiac condition

 Risk classification for exercise training: class C and above

 Severe respiratory condition

 Previous history of upper limb deep vein thrombosis

 Patients on glibenclamide or nicorandil- May affect RIPC

 Raynaud's Disease

 Contra indications for MRA

 Pregnancy

 Previous major limb amputation affect ability to exercise

['Remote Ischemic Preconditioning', 'Supervised Exercise', 'Standard Care']

Remote Ischemic Preconditioning
Supervised Exercise
Standard Care


Effect of Brain Lesion Severity on Treatment Response in Late-Life Depression

Summary: This study will determine the relationship between brain lesion severity, treatment response, and frontal lobe brain function in people with late-life depression (LLD).
Inclusion criteria: inclusion criteria:

 DSM-IV of major depressive disorder (MDD)

 Score of greater than 20 on the MADRS (score of greater than 17 for atypical depression)

 Score of greater than 20 on the Mini Mental State Examination (MMSE)

Exclusion criteria: :

 Any condition that may make having an MRI medically inadvisable

 Any severe or unstable medical conditions

 Any known primary neurological disorders, including history of stroke

 Any other simultaneous Axis I disorder

 History of substance or alcohol abuse disorder within 6 months prior to study entry

 Currently at risk for suicide

 History of failed prior adequate trials of two antidepressants for the current depressive episode

 History of failed prior adequate trial of sertraline

 Current use of any other psychoactive medications (medication washout will be required)


Fluorouracil, Cisplatin, and Radiation Therapy or Gemcitabine and Oxaliplatin in Treating Patients With Nonmetastatic Biliary Tract Cancer That Cannot Be Removed By Surgery

Summary: RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, oxaliplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving fluorouracil and cisplatin together with radiation therapy is more effective than giving gemcitabine together with oxaliplatin in treating nonmetastatic biliary tract cancer.~PURPOSE: This randomized phase II/III trial is studying fluorouracil, cisplatin, and radiation therapy to see how well they work compared to gemcitabine and oxaliplatin in treating patients with nonmetastatic biliary tract cancer that cannot be removed by surgery.
Inclusion criteria: DISEASE CHARACTERISTICS:

 Diagnosis of cancer of the biliary tract by 1 of the following methods:

 Histologic confirmation

 Stenosis of the biliary tract by MRI, CT scan, or ECHO

 Unresectable disease

 Amenable to radiotherapy

 No visceral metastases by imaging

 Hepatic adenopathies that can be included in a radiation field allowed

 No known ampulla of Vater or pancreatic cancer involving the biliary tract

 PATIENT CHARACTERISTICS:

 WHO performance status 0-2

 Creatinine < 1.5 mg/dL

 Absolute neutrophil count ≥ 1,500/mm^3

 Platelet count ≥ 75,000/mm^3

 Prothrombin time > 70%

 Bilirubin ≤ 2.9 mg/dL (after hepatic draining, if needed)

 No unstable angina

 No symptomatic cardiac insufficiency

 No other comorbidity that would preclude study therapy

 No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix

 No prior hydatid cyst or alveolar echinococciasis

 Not pregnant or nursing

 PRIOR CONCURRENT THERAPY:

 No recent biliary surgery

 No hepatic intra-arterial chemotherapy

 No prior anticancer therapy
Exclusion criteria:

['cisplatin', 'gemcitabine hydrochloride', 'oxaliplatin']

cisplatin
gemcitabine hydrochloride
oxaliplatin

['Extrahepatic Bile Duct Cancer', 'Gallbladder Cancer', 'Liver Cancer']

Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Liver Cancer


Research With Retinal Cells Derived From Stem Cells for Myopic Macular Degeneration

Summary: Pathologic myopia is a major cause of legal blindness worldwide. In myopic macular degeneration (MMD), there is degeneration of the retinal pigment epithelial (RPE) layer, and associated photoreceptors, resulting in vision loss. There is currently no standard treatment for MMD.~Transplantation of intact sheets of RPE and suspensions of isolated individual RPE cells as well as autologous translocation of RPE cells has been attempted as treatment for AMD. Human photoreceptors are comprised of two cell types-rods and cones. Both have a close relationship with the outermost retinal cells, the retinal pigmented epithelium (RPE). The RPE is located between the choroid and the photoreceptors. The RPE maintains photoreceptor function by recycling photopigments,delivering, metabolizing and storing vitamin A, phagocytosing rod photoreceptor outer segments, transporting iron and small molecules between retina and choroid, maintaining Bruch's membrane and absorbing stray light to allow better image resolution. In essence, the RPE layer is critical to the function and health of photoreceptors and the retina as a whole.~Human PRE (hRPE) transplantation may be a viable option for treatment of degenerative diseases of the retina.~MA09-hRPE cells are fully differentiated human RPE cells derived from embryonic stem cells. Transplanted hRPE cells prepared by Advanced Cell Technology have been studied in rodent models of macular degenerative disease. The data suggests that the subretinal injection of ACT's hRPE cell products rescues, or at least delays, loss of visual function in two animal models of retinal degenerative diseases.~The main purpose of this study is to evaluate the safety and tolerability of MA09-hRPE cellular therapy in patients with Myopic Macular Degeneration (MMD). Another objective is to evaluate potential efficacy endpoints to be used in future studies of RPE cellular therapy.
Inclusion criteria: inclusion criteria:

 Adult male or female over 40 years of age.

 Patient should be in sufficiently good health to reasonably expect survival for at least four years after treatment

 Axial myopia of equal to or greater than -8 diopters and/or axial length equal to or greater than 28 mm

 Clinical findings consistent with MMD with evidence of one or more areas of >250microns of geographic atrophy (as defined in the Age-Related eye Disease Study [AREDS] study) involving the central fovea.

 GA defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, and FA.

 No evidence of current or prior choroidal neovascularization

 The visual acuity of the eye to receive the transplant will be no better than 20/80.

 The visual acuity of the eye that is NOT to receive the transplant will be no worse than 20/400.

 The eye with the more advanced disease and worse vision will be the study eye.

 Electrophysiological findings consistent with macula-involving geographic atrophy.

 Medically suitable to undergo vitrectomy and subretinal injection.

 Medically suitable for general anesthesia or waking sedation, if needed.

 Medically suitable for transplantation of an embryonic stem cell line:

 Any laboratory value, which falls slightly outside of the normal range, will be reviewed by the Medical Monitor and Investigators to determine its clinical significance. If it is determined not to be clinically significant, the patient may be enrolled into the study.

 Normal serum chemistry (sequential multi-channel analyzer 20 [SMA-20]) and hematology (complete blood count [CBC], prothrombin time [PT], and activated partial thromboplastin time [aPTT]) screening tests. (NOTE:With the exception of abnormalities specifically identified in the
Exclusion criteria: )

 Negative urine screen for drugs of abuse.

 Negative human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) serologies.

 No history of malignancy (with the exception of successfully treated (excised) basal cell carcinoma[skin cancer] or successfully treated squamous cell carcinoma of the skin).

 Negative cancer screening within previous 6 months:

 complete history & physical examination;

 dermatological screening exam for malignant lesions;

 negative fecal occult blood test & negative colonoscopy within previous 7 years;

 negative chest roentgenogram (CXR);

 normal CBC & manual differential;

 negative urinalysis (U/A);

 normal thyroid exam;

 if male, normal testicular examination; digital rectal examination (DRE) and prostate specific antigen (PSA);

 if female, normal pelvic examination with Papanicolaou smear; and

 If female, normal clinical breast exam and, negative mammogram.

 If female and of childbearing potential, willing to use two effective forms of birth control during the study.

 If male, willing to use barrier and spermicidal contraception during the study.

 Willing to defer all future blood, blood component or tissue donation.

 Able to understand and willing to sign the informed consent.


Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease

Summary: Evaluate safety, tolerability, and pharmacokinetics of single doses of the investigational AAB-001 Vaccine in Japanese patients with Alzheimer's disease.
Inclusion criteria: inclusion criteria:

 Diagnosis of AD

 Age 50-85

 MMSE 14-26

 Other inclusion criteria Apply

Exclusion criteria: :

 Significant Neurological Disease

 Major Psychiatric Disorder

 Clinically Significant Systemic Illness

 Other


Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome

Summary: To investigate the long-term safety and tolerability of clobazam when administered for 1 year as adjunctive therapy in paediatric patients aged ≥1 to ≤16 years with Dravet Syndrome.
Inclusion criteria: The inclusion and
Exclusion criteria:  for the patients who participated in lead-in Study 14362A will be transferred from the 14362A study and for the patients who did not participate in lead-in Study 14362A the inclusion/exclusion is separately listed below.

 inclusion criteria:

 The patient has a diagnosis of Dravet Syndrome supported by:

 onset of seizures in the first year of life

 history of fever-induced prolonged seizures as determined by the Investigator

 these may include prolonged (approximately 15 minutes or longer) hemi-clonic seizures

 multiple seizure types which may include:

 generalised tonic-clonic (required for inclusion)

 clonic (required for inclusion)

 myoclonic jerks/seizures

 history of normal development prior to seizure onset followed by development delay or regression after seizure onset

 abnormal EEG consistent with Dravet Syndrome

 The patient is currently receiving a stable dose of clobazam of at least 0.5 mg/kg/day (maximum 20 mg/day) for at least 3 months

 Other protocol-defined inclusion and


Efficacy Study Of Tofacitinib In Pediatric JIA Population

Summary: Evaluate efficacy, safety and tolerability of tofacitinib in pediatric JIA patients.
Inclusion criteria: inclusion criteria:

 Male or female aged 2 to <18 years.

 Must meet International League Against Rheumatism (ILAR) JIA diagnostic criteria for one of the following categories with active disease for at least 6 weeks:

 Extended oligoarthritis;

 Polyarthritis (RF+);

 Polyarthritis (RF-);

 Systemic JIA with active arthritis but without active systemic features in the prior 6 months and at the time of enrollment;

 Psoriatic arthritis;

 Enthesitis related arthritis. Subjects with polyarticular course JIA (ie, extended oligoarthritis, polyarthritis RF+, polyarthritis RF , systemic JIA with active arthritis but without active systemic features) must have a minimum of 5 active joints (an active joint is defined as a joint with swelling or, in the absence of swelling, limited range of motion accompanied by either pain on motion or tenderness) at screening and baseline to be eligible for study entry.

 Subjects with psoriatic or enthesitis related arthritis must have a minimum of 3 active joints (an active joint is defined as a joint with swelling or, in the absence of swelling, limited range of motion accompanied by either pain on motion or tenderness) at screening and baseline to be eligible for study entry.

 Treatment with stable doses of a Non Steroidal Anti inflammatory Drug (NSAID) and/or a stable dose of an oral glucocorticoid, and/or a stable dose of methotrexate is permitted.

 For subjects receiving an oral glucocorticoid: Glucocorticoids may be administered at a maximum dose of 0.2 mg of prednisone equivalent per kilogram per day or 10 mg per day for ≥ 2 weeks before baseline, whichever is lower.

 For subjects receiving methotrexate (MTX) treatment: MTX may be administered either orally or parenterally at doses not to exceed 25 mg/wk or 20 mg/m2/week (whichever is lower); participants must have taken MTX for 3 months and be at a stable dose for at least 6 weeks before baseline. Subjects taking MTX must be taking folic acid or folinic acid in accordance with local standards.

 For subjects with psoriatic arthritis, the following topical treatments for psoriasis are allowed: non medicated emollients for use over the whole body; topical steroids including hydrocortisone and hydrocortisone acetate ≤1% for the palms, soles, face, and intertriginous areas only; tar, salicylic acid preparations, and shampoos free of corticosteroids are permitted only for the scalp

 Inadequate response or intolerance to at least one Disease Modifying Anti Rheumatic Drug (DMARD), which may include MTX or biologic agents; in the case of ERA and psoriatic arthritis, inadequate response to Non Steroidal Anti Inflammatory Drugs (NSAIDs).

 No evidence or history of untreated or inadequately treated active or latent tuberculosis (TB) infection as evidenced by the following:

 A negative QuantiFERON ®TB Gold In Tube test performed within the 3 months prior to screening. A negative purified protein derivative (PPD) test can be substituted for the QuantiFERON® TB Gold In Tube test only if the central laboratory is unable to perform the test or cannot determine the results to be positive or negative and the Pfizer medical monitor is informed and agrees on a case by case basis.

 Chest radiograph without changes suggestive of active tuberculosis (TB) infection within 3 months prior to screening is recommended and should be performed according to local standards of care or country-specific guidelines.

 No history of either untreated or inadequately treated latent or active TB infection.

 If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi drug resistant TB infection are <5% or an acceptable alternative regimen) or active (acceptable multi drug regimen) TB infection, neither a PPD test nor a QuantiFERON-Gold®TM test need be obtained. A chest radiograph should be obtained if not done within the 3 months prior to screening. To be considered eligible for the study, the chest radiograph must be negative for active tuberculosis infection.

 A subject who is currently being treated for latent TB infection can only be enrolled with confirmation of current incidence rates of multi-drug resistant TB infection, documentation of an adequate treatment regimen, and prior approval of the Sponsor.

 Fertile males and females who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must be willing and able to use a highly effective method of contraception as outlined in this protocol during the study and for at least 28 days after the last dose of study medication.

 6 Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

 7. Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study.

Exclusion criteria:

 Subjects with any of the following characteristics/conditions will not be included in the study:

 Previous JIA treatment with tofacitinib.

 Systemic JIA (sJIA) with active systemic features (including subjects with characteristic sJIA fever and rash or serositis within 6 months of enrollment).

 Persistent oligoarthritis.

 Undifferentiated JIA.

 Infections:

 Chronic infections;

 Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 6 months prior to the first dose of study drug;

 Any treated infections within 2 weeks of Baseline visit;

 A subject know to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C;

 History of infected joint prosthesis with prosthesis still in situ.

 History of recurrent (more than one episode) herpes zoster or disseminated (at least one episode) herpes zoster, or disseminated (at least one episode) herpes simplex.

 Active uveitis (according to SUN criteria) within 3 months of enrollment.

 Blood dyscrasias, including:

 Hemoglobin <10 g/dL or Hematocrit <33%;

 White Blood Cell count <3.0 x 109/L;

 Neutrophil count <1.2 x 109/L;

 Platelet count <100 x 109/L;

 Lymphocyte count <0.75 x 109/L.

 Estimated glomerular filtration rate [GFR] <40 mL/min/1.73 m2 at Screening. GFR will be calculated by the central lab using the bedside Schwartz formula.

 Current or recent history of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.

 Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1.5 times the upper limit of normal.

 History of any other rheumatologic disease, other than Sjogren's syndrome..

 History or current symptoms suggestive of lymphoproliferative disorders (eg, Epstein Barr Virus [EBV] related lymphoproliferative disorder, lymphoma, leukemia, or signs and symptoms of current lymphatic disease).

 Vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to the first dose of study drug, or is expected to be vaccinated or to have household exposure to these vaccines during treatment or during the 6 weeks following discontinuation of study drug.

 Subjects without documented evidence of having received at least one dose of the varicella vaccine in countries where the vaccine is approved and standard of care or those who do not have evidence of prior exposure to varicella zoster virus (VZV) based on serological testing (ie, VZV IgG Ab).

 Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ.

 Subjects who have previously failed more than 3 biologic therapies (with different mechanisms of action) for JIA.

 Subjects with a first degree relative with a hereditary immunodeficiency; IgA deficiency not exclusionary.

 Recent (within 28 days prior to first dose of study drug) significant trauma or major surgery.

 Subjects receiving potent and moderate CYP3A4 inhibitors or inducers.

 Prior treatment with non B cell specific lymphocyte depleting agents/therapies (eg, almetuzumab [CAMPATH], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc.). Subjects who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline and have normal CD 19/20+ counts by FACS analysis.

 Use of prohibited prescription or non prescription drugs and dietary supplements listed in Appendix 1 and Appendix 4 within the specified time frame prior to the first dose of study medication.

 Herbal supplements must be discontinued at least 28 days prior to the first dose of study medication.

 Use of certain biologic and non biologic DMARDs are disallowed at any time during this study (Appendix 1).

 For subjects with PsA, oral and topical medications and alternative treatments that could affect psoriasis are prohibited (see Inclusion Criterion 2 for exceptions). This includes topical corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids which must be discontinued at least 2 weeks prior to first dose of study drug. Also prohibited is ultraviolet B (UVB) (narrowband or broadband) phototherapy that must be discontinued at least 2 weeks prior to first dose of study drug. Psoralens + ultraviolet A (UVA) phototherapy (PUVA) must be discontinued at least 4 weeks prior to first dose of study drug.

 Subjects who are children of or related to investigational site staff members, site staff members otherwise supervised by the investigator, or Pfizer employees directly involved in the conduct of the study.

 Participation in other studies involving investigational drug(s) within 4 weeks or 5 half lives (whichever is longer) prior to study entry and/or during study participation. Exposure to investigational biologics should be discussed with the Sponsor.

 Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

 Pregnant or nursing females are excluded.


Elective vs Therapeutic Neck Dissection in Treatment of Early Node Negative Squamous Carcinoma of Oral Cavity

Summary: Cervical nodal metastasis is the single most important prognostic factor in head and neck cancers. Appropriate management of the neck is therefore of paramount importance in the treatment of these cancers. While it is obvious that the positive neck must be treated, controversy has always surrounded the clinically node negative neck with respect to the ideal treatment policy.The situation is difficult with regards to early cancers of the oral cavity (T1/T2). These cancers are usually treated with surgery where excision is through the per-oral route. Elective neck dissection in such a situation is an additional surgical procedure with its associated costs, prolonged hospitalization and may be unnecessary in as high as 80% of patients who finally turn out to be pathologically node negative. Should the neck be electively treated or there be a wait and watch policy? Current practice is that the neck is always addressed whenever there is an increased propensity to cervical metastasis or when patient follow-up is unreliable.~There is clearly a need therefore for a large randomized trial that will resolve the issue either way once and for all.~Primary Objective:~To demonstrate whether elective neck dissection (END) is equal or superior to the wait and watch policy i.e.~therapeutic neck dissection (TND) in the management of the clinically No neck in early T1 /T2 cancers of the oral cavity.~Secondary Objective:~Does Ultrasound examination have any role in the routine initial workup of a node negative patient?~How are patients ideally followed up -does sonography have a role or is clinical examination sufficient.~Is assessment of tumor thickness by the surgeon at the time of initial surgery accurate -Is there a correlation~Identify histological prognostic factors in the primary that may help identify a sub-set of patients at an increased risk for cervical metastasis.
Inclusion criteria: inclusion criteria:

 Histologically proven T1 or T2 N0 M0 (clinical) squamous cell carcinoma of the buccal mucosa, lower alveolus, oral tongue and floor of mouth.

 Surgery is the preferred treatment and the primary tumor can be excised with clear margins via the per-oral route.

 No history of a prior malignancy in the head and neck region.

 No prior malignancy outside the head and neck region in the preceding 5 years.

 Patient will be reliable for follow-up

 Age> 18 years and < 75 years.

 No significant co-morbid conditions - ASA grade II and I.

 Understands the protocol and is able to give informed consent.

Exclusion criteria: :

 Prior radiotherapy or surgery for malignancy in the head and neck region.

 Non squamous cell carcinomas of the oral cavity.

 Upper alveolus and palatal lesions where there is a possibility of retropharyngeal node involvement.

 Per-oral excision of tumor will compromise margins in the opinion of the treating surgeon.

 Significant co-existing pre-malignant conditions like erytho-leucoplakia and oral sub mucous fibrosis that in the opinion of the clinician would interfere in the planned treatment management of the patient.

['Elective neck dissection in early oral cancer', 'Therapeutic Neck Dissection']


Treatment of Distal Radius Buckle Fractures

Summary: This study determines if patients with buckle fractures of the distal radius and/or ulna treated with supportive care only demonstrate non-inferior outcomes in regard to pain control during healing, functional outcome at the wrist joint, and parental satisfaction, when compared with patients treated with the standard treatment regimen of 3-4 weeks in a short arm cast.
Inclusion criteria: inclusion criteria:

 Children age 1-17 with buckle fractures of the distal radius and/or ulna. -

Exclusion criteria: :

 Patients are excluded if there is any other injury to the upper limb or serious bodily trauma that might complicate pain scores. Children with suspected or proven metabolic bone disease, or pathologic fractures are excluded due to resultant abnormal bone healing.


Timing of Surgical Intervention in Buruli Ulcer Patients Treated With Antibiotics

Summary: SUMMARY~Rationale: Buruli ulcer, caused by Mycobacterium ulcerans, is an ulcerative disease endemic in West Africa. It often leads to functional limitations. Treatment was by extensive surgery, until in 2005 gradually antibiotic treatment for eight weeks with rifampicin and streptomycin was added. Observation of Buruli ulcer lesions of limited size during antibiotic treatment showed that during treatment there is a paradoxical increase of the lesion, with a decrease of the lesion after week 14. Current WHO protocols advise to decide whether surgery is needed four weeks after the start of antibiotics. This might be too early in the healing process. The investigators hypothesize that delay in surgery is safe, and that it results in a reduction of the number of surgical interventions.~Objectives:~Primary Objective of this study is to compare the need for surgical treatment in standard timing of surgery at the end of eight weeks antimicrobial treatment with a policy to postpone surgical treatment until week 14.~Secondary Objectives are to study whether postponing surgery leads to less extensive surgery and a change in frequency of functional limitations;~Study design:~Patients will be randomized for surgery at week 8 after start of antibiotic treatment and week 14 after start of treatment. Reasons for treating doctors to decide to intervene with surgery will be according to current clinical practice and will be clearly defined in this protocol. Standard care of eight weeks of rifampicin and streptomycin will be given. All patients will be followed and lesional size using acetate sheet recordings will be used during follow-up.~Study population: Patients with a clinical picture of Buruli ulcer disease confirmed by diagnostic tests in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin. Patients who are pregnant, have a contraindication for general anaesthesia and children below three years old will be excluded. 130 Patients in each treatment arm will be included to detect a difference in percentage of patients needing surgery of 20 percent.~Main study parameters/endpoints: Primary outcome measure is the number of patients healed without surgery. Secondary outcome measures are the extent of surgery by measurement of lesional size, functional limitations after the end of treatment and one year after the start of treatment and the duration of admission.
Inclusion criteria: inclusion criteria:

 Patients with a clinical picture of Buruli ulcer disease in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin, will be included at start of antibiotic treatment.

 All stages of the disease will be included. Only patients with confirmed disease by direct microscopy following acid-fast staining or PCR will be included.

Exclusion criteria: :

 Patients not on the standard treatment of eight weeks of rifampicin and streptomycin for any reason, will be excluded from this study.

 Treatment with macrolide or quinolone antibiotics, or antituberculous medication, or immune-modulatory drugs including corticosteroids within the previous one month.

 Patients not compliant with the antibiotic therapy will be excluded as well. Non-compliance is defined as the use of < 70 % of the prescribed antibiotics.

 Patients with a contraindication for general anaesthesia are not able to participate.

 Pregnancy.

 Osteomyelitis.

 Lesion close to the eye, with preferred standard treatment to wait for effect antibiotic treatment on extent surgery.

 The BUFLS (Buruli ulcer functional limitation score) cannot be applied to children below three years and therefore will not participate.

 Patients reporting to refuse surgery at any point in the intended treatment, cannot be included.

 Any situation or condition which may compromise ability to comply with the trial procedures.

 Patients known to be HIV positive.

 Lack of willingness to give informed consent (and/or assent by parent/legal representative).

['surgical intervention on Buruli ulcer']

['Mycobacterium Ulcerans Disease', 'Buruli Ulcer']

Mycobacterium Ulcerans Disease
Buruli Ulcer


Randomized Comparison of MynxGrip Vascular Closure Device and Manual Compression for Closure After Femoral Access Angiography. The Closure Devices Used in Every Day Practice Study, CLOSE-UP III Trial

Summary: Is the MynxGrip (test device) non-inferior to manuel compression (standard comparator) in the incidence of adverse access site related events in-hospital, at 30 days and at 6 months.
Inclusion criteria: inclusion criteria:

 >18 year

 Should be able to provide valid informed signed consent

 CAG, possibly including intracoronary measurement (FFR) or intracoronary imaging (IVUS, optical coherence tomography (OCT), NIRS)

Exclusion criteria: :

 Percutaneous coronary intervention (PCI) procedure and/or implantation of stents

 ST-Elevations Myocardial Infarction (STEMI)

 Multiple punctures

 Active infection

 Groin haematoma before the closure procedure

 Known pseudoaneurysm or arteriovenous (AV) fistula in the ipsilateral groin

 Cardiogenic shock

 Prior peripheral arterial surgery in abdomen or lower extremities

 Sheat size >7 F

 Life expectancy less than one year

 Possible pregnancy or positive pregnancy test or breastfeeding women

 Simultaneous or planned subsequent femoral vein access

 Allergy to any of the components in the closure material left in the groin

 Puncture or closure with closure device at same site < 30 days

 Puncture or closure with manuel compression at same site < 5 days

 Patients with peripheral artery disease can be included at operators discretion except if heavy calcification is present at the access site, which at the operators discretion precludes insertion of the closure device


Clarithromycin Modified Release Observational Study for Evaluation of Treatment, Tolerability & Recovery Time in Saudi & Egyptian Clinical Settings (CLOSER)

Summary: The objective is to describe the time to recovery of symptoms (cough, mucus, fever, sore throat, and others), tolerability and compliance of treatment with clarithromycin once daily in patients with upper or lower respiratory tract infections in the routine clinical practice.
Inclusion criteria: inclusion criteria:

 Adults, equal to or more than 18 years years of age

 Patients with respiratory tract infections, including any of the following:

 Acute tracheitis, acute tracheobronchitis

 Acute sinusitis

 Chronic sinusitis

 Acute tonsillopharyngitis

 Acute bronchitis

 Mild community-acquired pneumonia

 Acute exacerbation of chronic bronchitis

Exclusion criteria: :

 Known hypersensitivity to or previously intolerant of macrolides.

 Illness severe enough to warrant hospitalization or parenteral therapy.

 Concomitant use of any of the following medications:

 Drugs metabolized by CYP3A isozyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporin, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (e.g. warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam and vinblastine.

 Drugs metabolized by other isozymes within CYP450 system: phenytoin, theophylline and valproate.

 Colchicine, Digoxin, Some antiretrovirals: zidovudine and ritonavir.

 Severe immunodeficiency and chronic disease conditions.

 Renal or hepatic impairment (creatinine clearance under 30 mL/min, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) equal or more than 3x higher level in comparison with the norm).

 Mental condition rendering the subject unable to understand the nature of the study.

['clarithromycin modified release 500 mg']


A Study of the Efficacy and Safety of Desloratadine (MK-4117) in Japanese Participants With Perennial Allergic Rhinitis (MK-4117-200)

Summary: This is a study to evaluate the efficacy and safety of desloratadine (MK-4117) in Japanese participants with perennial allergic rhinitis. The primary hypothesis is that desloratadine is superior to placebo after 2 weeks of treatment with regard to change from baseline in Total Nasal Symptom Score among Japanese participants with perennial allergic rhinitis.
Inclusion criteria: inclusion criteria:

 Diagnosed with perennial allergic rhinitis

 Outpatient.

Exclusion criteria: :

 Lower respiratory tract infection or nasopharyngolaryngeal infection (acute upper respiratory tract infection, acute pharyngolaryngitis, or acute tonsillitis, etc.)

 Coexisting infections or systemic mycosis for which there are no effective antibiotics

 Asthma complication under treatment

 Nasal septum ulcers, nasal surgery, or nasal trauma, which has not healed

 Vasomotor rhinitis or eosinophilic rhinitis

 Nasal conditions (infectious sinusitis, hypertrophic rhinitis, acute or chronic rhinitis, nasal polyps, septal deviation, etc.) which may interfere with the evaluation of the efficacy of the study drug

 History of hypersensitivity to antihistamines or study drug

 Currently receiving treatment with another investigational drug or has received an investigational drug in the past 3 months

 Has started specific desensitization therapy or nonspecific allassotherapy (Histaglobin, vaccine therapy, etc.) or who had discontinued such therapies within 90 days (3 months) before the day of obtaining informed consent

 Severe hepatic, renal, cardiac, hematological disease, or other serious coexisting diseases and whose general condition is poor

 History of malignancy or clinically important hematological disorder

 History of severe drug allergy (e.g., anaphylactoid reaction).