Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery

Summary: This randomized phase III trial studies how well gefitinib works in treating patients with stage IB, II, or IIIA non-small cell lung cancer that was completely removed by surgery. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if gefitinib may be an effective treatment in preventing tumors from returning after they have been removed by surgery.
Inclusion criteria: inclusion criteria:

 Patients must have histological proof of a primary non-small cell lung cancer (bronchoalveolar carcinomas presenting as a discrete solitary radiological mass or nodule are eligible)

 Patients must be classified post-operatively as stage IB, II or IIIA on the basis of pathologic criteria

 At the time of resection a complete mediastinal lymph node resection or at least lymph node sampling should have been attempted; if a complete mediastinal lymph node resection or lymph node sampling was not undertaken, any mediastinal lymph node which measured 1.5 cm or more on the pre-surgical computed tomography (CT)/magnetic resonance imaging (MRI) scan or any area of increased uptake in the mediastinum on a pre-surgical positron emission tomography (PET) scan must have been biopsied; note: a pre-surgical PET scan is not mandatory

 The nodal tissue must be labelled according to the recommendations of the American Thoracic Society; surgeons are encouraged to dissect or sample all accessible nodal levels; the desirable levels for biopsy are:

 Right upper lobe: 4, 7, 10

 Right middle lobe: 4, 7, 10

 Right lower lobe: 4, 7, 9, 10

 Left upper lobe: 5, 6, 7, 10

 Left lower lobe: 7, 9, 10

 Surgery may consist of lobectomy, sleeve resection, bilobectomy or pneumonectomy as determined by the attending surgeon based on the intraoperative findings; patients who have had only segmentectomies or wedge resections are not eligible for this study; all gross disease must have been removed at the end of surgery; all surgical margins of resection must be negative for tumor

 No more than 16 weeks may have elapsed between surgery and randomization; for patients who received post-operative adjuvant platinum-based chemotherapy, no more than 26 weeks may have elapsed between surgery and randomization

 Patient must consent to provision of and investigator(s) must agree to submit a representative formalin fixed paraffin block of tumor tissue at the request of the Central Tumor Bank in order that the specific EGFR correlative marker assays may be conducted

 The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

 Leukocytes >= 3.0 x 10^9/L or >= 3000/ul

 Absolute granulocyte count >= 1.5 x 10^9/L or >= 1,500/ul

 Platelets >= 100 x 10^9/L or >= 100,000/ul

 Total bilirubin within normal institutional limits

 Alkaline phosphatase =< 2.5 x institutional upper limit of normal; if alkaline phosphatase is greater than the institutional upper limit of normal (UNL) but less than the maximum allowed, an abdominal (including liver) ultrasound, CT or MRI scan and a radionuclide bone scan must be performed prior to randomization to rule out metastatic disease; if the values are greater than the maximum allowed, patients will not be considered eligible regardless of findings on any supplementary imaging

 Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal; if AST (SGOT) or ALT (SGPT) are greater than the institutional upper limit of normal (UNL) but less than the maximum allowed, an abdominal (including liver) ultrasound, CT or MRI scan must be performed prior to randomization to rule out metastatic disease; if the values are greater than the maximum allowed, patients will not be considered eligible regardless of findings on any supplementary imaging

 Patient must have a chest x-ray done within 14 days prior to randomization; patient must have a CT or MRI scan of the chest done within 90 days prior to surgical resection if at least one of the following was undertaken:

 A complete mediastinal lymph node resection; or

 Biopsy of all desired levels of lymph nodes - as specified above; or

 A pre-surgical PET scan within 60 days prior to surgical resection If none of the above was undertaken then the CT or MRI scan of the chest must have been performed within 60 days prior to surgical resection Note: a pre-surgical PET scan is not mandatory

 Patient must have an electrocardiogram (EKG) done within 14 days prior to randomization

 Women of childbearing age and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and while taking study medication and for a period of three months after final dose; should a woman become pregnant or suspect she is pregnant while she or her male partner are participating in this study, she should inform her treating physician immediately

 Patients may receive post-operative radiation therapy; patients must have completed radiation at least 3 weeks prior to randomization and have recovered from all radiation-induced toxicity; patients who have received radiation therapy should also be randomized within 16 weeks of surgery

 Patient consent must be obtained according to local institutional and/or University Human Experimentation Committee requirements; it will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to either the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) study coordinator (for NCIC CTG centers) or the Cancer Trials Support Unit (CTSU) (for all other investigators), that such clearance has been obtained, before the trial can commence in that center; a standard consent form for the trial will not be provided, but a sample form is given; this sample consent form has been approved by the National Cancer Institute (NCI) Central Institutional Review Board (IRB) and must be used unaltered by those CTSI centers which operate under CIRB authority; for NCIC CTG centers, a copy of the initial full board Research Ethics Board (REB) approval and approved consent form must be sent to the NCIC CTG central office; please note that the consent form for this study must contain a statement which gives permission for the government agencies, NCI, NCIC CTG and monitoring agencies to review patient records

 NCIC-CTG Centers: the patient must have the ability to understand and the willingness to sign a written informed consent document; the patient must sign the consent form prior to randomization

 CTSU Centers: the patient, or in the case of a mentally incompetent patient his or her legally authorized and qualified representative, must have the ability to understand and the willingness to sign a written informed consent document; the consent form must be signed prior to randomization

 Patients must be accessible for treatment and follow-up; investigators must assure themselves that patients registered on this trial will be available for complete documentation of the treatment administered, toxicity and follow-up

 Initiation of protocol treatment must begin within 10 working days of patient randomization

 Patients may have received post-operative adjuvant platinum-based chemotherapy; patients must have completed chemotherapy at least 3 weeks prior to randomization and have recovered from all chemotherapy-induced toxicity; patients who have received adjuvant chemotherapy should also be randomized within 26 weeks of surgery

Exclusion criteria: :

 Prior or concurrent malignancies; patients who have had a previous diagnosis of cancer, if they remain free of recurrence and metastases five years or more following the end of treatment and, in the opinion of the treating physician do not have a substantial risk of recurrence of the prior malignancy, are eligible for the study; patients who have been adequately treated for non-melanomatous skin cancer or carcinoma in situ of the cervix are eligible irrespective of when that treatment was given

 A combination of small cell and non-small cell carcinomas or a pulmonary carcinoid tumor

 More than one discrete area of apparent primary cancer (even if within the same lobe, T4, IIIB)

 Clinically significant or untreated ophthalmologic (e.g. Sjogren's etc.) or gastrointestinal conditions (e.g. Crohn's disease, ulcerative colitis)

 Any active pathological condition that would render the protocol treatment dangerous such as: uncontrolled congestive heart failure, angina, or arrhythmias, active uncontrolled infection, or others

 A history of psychiatric or neurological disorder that would make the obtainment of informed consent problematic or that would limit compliance with study requirements

 Patient, if female, is pregnant or breast-feeding

 Neoadjuvant chemotherapy or immunotherapy for NSCLC; however, patients may have received pre-operative limited field, low dose (less than 1000 cGy) external beam radiation therapy or endobronchial brachytherapy or laser therapy for short term control of hemoptysis or lobar obstruction; full dose pre-operative radiotherapy of curative intent is a cause for exclusion; patients may have received post-operative adjuvant platinum-based chemotherapy however non-platinum-based chemotherapy is a cause for exclusion

 History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used on this trial; patients with ongoing use of phenytoin, carbamazepine, barbiturates, rifampicin, or St John's Wort are excluded

 Incomplete healing from previous oncologic or other major surgery

['gefitinib', 'placebo', 'laboratory biomarker analysis']

gefitinib
placebo
laboratory biomarker analysis

['Adenocarcinoma of the Lung', 'Adenosquamous Cell Lung Cancer', 'Bronchoalveolar Cell Lung Cancer', 'Large Cell Lung Cancer', 'Squamous Cell Lung Cancer', 'Stage IB Non-small Cell Lung Cancer', 'Stage IIA Non-small Cell Lung Cancer', 'Stage IIB Non-small Cell Lung Cancer', 'Stage IIIA Non-small Cell Lung Cancer']

Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Bronchoalveolar Cell Lung Cancer
Large Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IB Non-small Cell Lung Cancer
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer


Comparison of Combination Olanzapine+Lithium or Chlorpromazine+Lithium in Treatment of First Manic Episode With Psychotic Features

Summary: Aim: In a population of first episode manic patients with psychotic features, we want to compare the side effect profile, the degree of adherence and the subjective well being, as well as the efficacy of two treatments: The standard treatment currently applied (lithium + chlorpromazine) and an alternative treatment more recently introduced (lithium + olanzapine). In addition, we want to study retrospectively the development of bipolar disorder and study prospectively the 6 and 12-month outcome of a cohort of patients presenting a first manic episode with psychotic features.~Research Background: While the efficacy of lithium in the treatment of acute mania has been established by numerous studies, it is also known that up to 50% of the patients fail to respond when it is prescribed alone. It is therefore common practice to complement the treatment, most commonly with antipsychotics and benzodiazepines. It has been suggested that antipsychotic agents are faster acting and are superior in controlling hyperactivity compared to lithium, whereas mood stabilisation is better achieved by lithium, Typical antipsychotics, such as chlorpromazine, may therefore be useful as adjunctive medication to mood stabilisers, especially within the first few weeks of treatment of acute mania, and for patients exhibiting psychotic symptoms or hyperactivity. They however can induce side effects (somnolence, dizziness, dry mouth, extrapyramidal side effects such as rigidity of the muscles, and possibly tardive dyskinesia (involuntary movements or contraction of muscles), as well as akathysia (sense of restlessness). They finally have been suspected to contribute to the occurrence of post-manic depression. Recent publications in chronic populations have shown that atypical antipsychotics, such as olanzapine, are also an effective adjunctive treatment. Olanzapine has the important advantage to induce a very low incidence of extrapyramidal side effects, including tardive dyskinesia. It can however induce somnolence, dizziness, dry mouth, and rather commonly weight gain. Moreover, some authors have reported that olanzapine might induce mania. Both treatments appear then to have positive effects as well as undesirable side effects. Our project is to compare them. The literature concerning first episode mania is sparse, particularly in the domain of pharmacotherapy. One retrospective study showed that 77% of the patients received antipsychotics at discharge and 25% at 6 months follow-up. No comparison has however been made between typical and atypical antipsychotics, and there are no specific treatment guidelines of first episode mania with psychotic features.~Project Summary: The hypothesis is that olanzapine and chlorpromazine will have a comparable efficacy as adjunctive treatment of the acute manic episode with psychotic features. We however think olanzapine will induce less side effects and will be better accepted by the patients, and therefore that the adherence to the treatment will be better than with chlorpromazine. We finally think the subjective sense of well being will be greater with olanzapine than with chlorpromazine.We will recruit 75 patients at the time of their first admission for mania with psychotic features at EPPIC. After signature of the informed consent, we will perform a baseline assessment first to confirm the diagnosis, and second to evaluate the level of psychopathology. The patients will then be randomly selected to receive either a treatment of lithium and olanzapine or a treatment of lithium and chlorpromazine. By the end of the study there will be 37 patients in each group.The patients will go through a baseline assessment including physical examination and usual laboratory investigation to exclude any physical illness. They will also go through a one-hour assessment of psychopathology. Between day 2 and 3 they will go through 2 hours of interview to reassess diagnosis and personal history. They will thereafter be assessed weekly for eight weeks on various dimensions: evolution of the intensity of the symptoms, appearance of depressive symptoms, occurrence of side effects and degree of adherence to the treatment, in an 1-hour interview. Subjective well being and quality of life will re evaluated at week 4 and 8, adding 45 minutes to the duration of the interview. This is a flexible dose, open trial, which means the doctor in charge of the patient will know which medication is being prescribed, and that he will be allowed to adapt the dosage according to what he feels necessary. This research project will allow us to organise a more specialised clinic for the care of first episode manic patients. We will take this opportunity to study carefully the months preceding the appearance of the first episode in order to try to reconstruct the prodrome of bipolar disorders. We will also, in an extension phase of the study, look at the long term outcome (at 6 and 12 months) of a first episode of mania.
Inclusion criteria: inclusion criteria:

 Male and female patients aged 15 to 29.

 Experiencing a first episode psychosis.

 Meet DSM-IV criteria for bipolar either manic or mixed episode, or schizoaffective disorder manic episode.

 Minimum score of 20 on the YMRS

 Written informed consent to participation.

Exclusion criteria: :

 Patients at immediate risk of committing harm to self or others

 Use of neuroleptics or mood-stabilisers in the two months preceding admission to EPPIC

 Organic mental disease, including mental retardation

 History of clinically significant illness (liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological or metabolic disturbances).

 Clinically relevant biochemical or hematological abnormalities.

 Pregnant or lactating woman

 History of epilepsy

 History of severe drug allergy or hypersensitivity

 Non fluency in English.

['Bipolar Disorder', 'Schizoaffective Disorder']

Bipolar Disorder
Schizoaffective Disorder


Mechanism of tDCS-induced Learning Enhancement - the Role of Serotonin

Summary: The aim of this study is to assess whether the application of a selective serotonin reuptake inhibitor (SSRI) enhances and prolongs the learning enhancement achieved by anodal transcranial direct current stimulation (atDCS). For this, young and older healthy subjects will be tested with a well established learning paradigm. Results of this study may help to support the application of atDCS also in patients, e.g. with dementia or mild cognitive impairment.
Inclusion criteria: inclusion criteria:

 right handedness

 unobtrusive neuropsychological screening

 ability to provide written informed consent

 no pathological findings in head MRI

 age: 18 to 35 years (young adults) or 50-80 years (older adults)

 Highly effective contraception (Pearl Index < 1) or reliable abstinence from any heterosexual relationships in women of childbearing potential

Exclusion criteria: :

 severe internal or psychiatric disease (especially depression or suicidal thoughts)

 epilepsy

 cognitive impairment (< SD under age adjusted norm in neuropsychological testing)

 concurrent taking of serotonin precursors (tryptophan, 5-HTP) or MAO inhibitors

 concurrent taking of tramadol or triptans

 concurrent taking of pimozide or linezolid

 concurrent taking of other drugs prolonging the QT-interval

 long-QT-syndrome

 hypokalemia or hypomagnesemia

 known intolerance of the study medication

 claustrophobia or metallic implants, tattoos (MRI

['tDCS', 'Citalopram', 'sham-tDCS + placebo']


Microwave Ablation and Partial Splenic Embolization in the Management of Hypersplenism

Summary: The aim of this study is to compare microwave thermal coagulation and partial splenic embolization in the management of hypersplenism in patients with cirrhosis.~This study will be conducted on 40 patients with liver cirrhosis associated with splenomegaly and hypersplenism. The study will be done at the National Hepatology and Tropical Medicine Research Institute.
Inclusion criteria: inclusion criteria:

 Liver Cirrhosis

 Hypersplenism

Exclusion criteria: :

 Patients with bad performance scale.

 Patients with hepatic encephalopathy and tense ascites.

 Patient with active esophageal variceal bleeding .

 Patients with hypocellular bone marrow (BM).

 Patients with renal failure.

['Microwave Thermal Coagulation', 'Partial Splenic Embolization']

Microwave Thermal Coagulation
Partial Splenic Embolization


Minimally Invasive Total Knee Replacement - Navigated Versus Non-navigated Study

Summary: The primary objective of this investigation is to compare the precision of long leg alignment achieved by the two types of procedure. The secondary objectives of this investigation are to:~Compare the accuracy of long leg alignment achieved by the two types of procedure.~Compare the number of optimal implantations achieved by the two types of procedure.~Compare the clinical performance of the knee replacement in subjects who have undergone one of the two types of procedure.~Compare the functional outcome achieved by subjects who have undergone one of the two types of procedure.~Compare the interface radiographic appearance 5 years post-operatively between the two types of procedure.~Compare the accuracy and precision of long leg alignment achieved by the two types of procedure 5 years post-operatively, i.e., at final follow-up and also the change in accuracy and precision between the final follow-up and baseline.~Compare the Adverse Events experienced by the subjects who have undergone the two types of procedure.
Inclusion criteria: inclusion criteria:

 Male or female subjects aged between 18 and 80 years inclusive.

 Subjects who require a primary total knee replacement and are considered by the Investigator to be suitable for the specific knee prosthesis identified in the protocol.

 Subjects who are able to give and have given voluntary, written informed consent to participate in this clinical investigation.

 Subjects who have given consent to the transfer of his/her information to DePuy.

 Subjects who, in the opinion of the Clinical Investigator, are able to understand this clinical investigation, co-operate with the investigational procedures and are willing to return to the hospital for all the required post-operative follow-ups.

Exclusion criteria: :

 Subjects who have a pre-operative limb deformity of equal to or greater than 10° varus or 15° valgus as defined using the anatomical axis.

 Subjects who have a fixed flexion contracture of greater than 10º.

 Subjects who are clinically obese i.e. BMI ≥30.

 Subjects who have, in the opinion of the Investigator, an existing condition that would compromise their participation and follow-up in this study.

 Female subjects who are pregnant or lactating.

 Subjects who are known drug or alcohol abusers or have a psychological disorder that could affect follow-up care or treatment outcomes.

 Subjects who have participated in a clinical investigation with an investigational product in the last 3 months.

 Subjects currently involved in any personal injury litigation, medical-legal or worker's compensations claims.

 Subjects who have previously had a prosthetic knee replacement device (any type) of the affected knee.

 Subjects who present with ankylosis of the hip joint on the side to be treated or previous ipsilateral Upper Tibial Osteotomy/High Tibial Osteotomy.

 Subjects who require simultaneous bilateral total knee replacements.

 Subjects who have had a contralateral TKA performed less than six months before the proposed TKA.

 Subjects who have had a contralateral TKA and that knee was previously entered in the study.

 Subjects who, in the opinion of the surgeon, will require a contralateral TKA within 6 months of the index procedure.

 Subjects in whom the surgeon intends to implant a knee component that is not one of those listed in Table 1.

 Subjects who have inflammatory arthritis.

['Either P.F.C. Sigma or L.C.S. Complete knee replacement using the conventional surgical approach and manual surgical technique', 'Either P.F.C. Sigma or L.C.S. Complete knee replacement using minimally invasive surgical approach and computer navigation']


Appendicitis With Medical Treatment

Summary: prospective study to collect data of patients with appendicitis, not receiving operation
Inclusion criteria: inclusion criteria:patients with appendicitis, not receiving operation -

Exclusion criteria: :nil

 -


Plug Arterial Closure System (PACS, 7F)

Summary: The purpose of this study is to assess the safety and feasibility of the 7F Ensure Medical Vascular Closure Devices to facilitate hemostasis in patients undergoing diagnostic or interventional coronary procedures using a standard 7F introducer sheath.
Inclusion criteria: inclusion criteria:

 Scheduled for a coronary diagnostic or interventional procedure

 Able to undergo emergent vascular surgery if a complication requires it

 7F arterial puncture located in the common femoral artery

 Femoral artery has a lumen diameter of at least 5 mm

Exclusion criteria: :

 Arterial puncture in the femoral artery of both legs

 Prior target artery closure with any vascular closure device, or closure with manual compression within 30 days prior to catheterization

 Patients who bruise or bleed easily or with a history of significant bleeding or platelet disorders

 Acute ST-elevation myocardial infarction within 48 hours prior to catheterization

 Uncontrolled hypertension at time of vessel closure

 Elevated Activated Clotting Time at time of vessel closure

 Ineligible for in-catheterization lab introducer sheath removal

 Concurrent participation in another investigational device or drug trial

 Thrombolytic therapy, bivalirudin, other thrombin-specific anticoagulants, or low molecular weight heparin within 24 hours prior to catheterization

 Preexisting hematoma, arteriovenous fistula, or pseudoaneurysm at the vessel access site prior to femoral artery closure

 Prior femoral vascular surgery or vascular graft in region of access site

 Femoral artery is tortuous or requires an introducer sheath longer than 11 cm

 Fluoroscopically visible calcium, atherosclerotic disease, or stent within 1 cm of the puncture site that would interfere with the operation of the experimental device

 Difficulty in obtaining vascular access resulting in multiple arterial punctures and/or posterior arterial puncture

 Antegrade vascular puncture

 Body Mass Index over 40 kg/m2

 Symptomatic leg ischemia in the target limb including severe claudication or weak/absent pulse

 Femoral artery diameter stenosis exceeding 50%

 Pre-existing severe non-cardiac systemic disease or terminal illness

 Planned arterial access at the same access site within 30 days of catheterization

 Extended hospitalization (e.g. CABG surgery)

 Pre-existing systemic or cutaneous infection

 Prior use of an intra-aortic balloon pump through the arterial access site

 Cardiogenic shock during or immediately following the catheterization

 Patient is unable to ambulate at baseline

 Patient is known or suspected to be pregnant or is lactating

 Patient is unavailable for follow-up

 Any angiographic or clinical evidence that the physician feels would place the patient at increased risk with the use of the experimental device

['Vascular access site closure (7F Ensure)']

['Angioplasty, Transluminal, Percutaneous Coronary', 'Coronary Arteriosclerosis']

Angioplasty
Transluminal
Percutaneous Coronary
Coronary Arteriosclerosis


Trial of Third Party Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation

Summary: The purpose of this study is to see how well transfusions of T-cells work in treating CMV. Tcells are a type of white blood cell that helps protect the body from infection. A transfusion is the process by which blood from one person is transferred to the blood of another. In this case, the T-cells are made from the blood of donors who are immune to CMV. The T-cells are then grown and taught to attack the CMV virus in a lab.
Inclusion criteria: inclusion criteria:

 Each patient must satisfy at least one of the following criteria:

 The patient must have a clinically documented condition associated with CMV (e.g. interstitial pneumonia, hepatitis, retinitis, colitis) Or

 The patient must have microbiological evidence of CMV viremia or tissue invasion as attested by viral culture, or detection of levels of CMV DNA in the blood or body fluids consistent with CMV infection.

 Patient must also satisfy at least one of the following criteria:

 The patient's CMV infection is clinically progressing or CMV viremia is persistent or increasing (as evidenced by quantitation of CMV DNA in the blood) despite two weeks induction therapy with antiviral drugs.

 Or

 The patient has developed CMV viremia as attested by viral culture, or detection of levels of CMV DNA in blood or body fluids while receiving prophylactic doses of antiviral drugs to prevent CMV infection post transplant.

 Or

 The patient is unable to sustain treatment with antiviral drugs due to drug associated toxicities (e.g. myelosuppression [ANC< 1000μl/ml without GCSF support] or nephrotoxicity [corrected creatinine clearance ≤ 60 ml/min/1.73 m^2 or serum creatinine > 2 mg/dl]) CMV infections are life threatening, and may involve multiple organ systems such as the lungs, liver, gastrointestinal tract, hematopoietic and central nervous systems. Antiviral drugs used for treatment may also compromise renal and hematopoietic function. Therefore, dysfunctions of these organs will not affect eligibility for this protocol.

 Patients must meet the following clinical criteria to receive CMVpp65-CTL infusions

 Stable blood pressure and circulation, not requiring pressor support

 Evidence of adequate cardiac function as demonstrated by EKG and/or echocardiography.

 A life expectancy of at least 3 weeks, even if requiring artificial ventilation.

 There are no age restrictions

 Patient must also satisfy at least one of the following criteria:

 The patient's HCT donor has not been previously infected by or sensitized to CMV (e.g. a cord blood transplant or a marrow or PBSC transplant from a seronegative donor).

 The patient's HCT donor, if seropositive, is either not available or not willing to provide leukocytes for generation of CMV-specific T-cells.

 There are CMVpp65-specific T-cells available in appropriate doses in the MSKCC Adoptive Immune T-cell Therapy Bank that are matched with the patient for 1 HLA allele and that exhibit CMVpp65-specific cytotoxic activity that is restricted by an HLA allele shared by the patient

Exclusion criteria: :

 Patients requiring high doses of glucocorticosteroids (≥ 0.3 mg/kg prednisone or its equivalent)

 Patients who are moribund

 Patients with other conditions not related to CMV infection (e.g. uncontrolled bacterial sepsis or invasive fungal infection) which are also life-threatening and which would preclude evaluation of the effects of a T-cell infusion.

 Patients who are pregnant

['CMV Infection', 'Persistent CMV Viremia']


Long Term Effects of Erythrocyte Lysis

Summary: In this prospective observational trial, participants with chronic hemolysis will be assessed with echocardiogram for elevated tricuspid jet velocity and other evidence of pulmonary hypertension. Participants will have laboratory studies evaluating: severity of hemolysis, splenic function, inflammation, endothelial dysfunction, and hypercoagulability. There will be 3 main categories of participants enrolled in this study: (1) pediatric participants with severe sickle cell disease (SCD) (HbSS, HbS/β° thalassemia ) who are not receiving treatment (e.g., hydroxyurea or chronic transfusions); (2) pediatric participants with other forms of SCD or severe SCD (HbSS, HbS/β° thalassemia) patients being treated with hydroxyurea or chronic transfusions; and (3) pediatric and adult participants with other non-sickling hematological disorders.
Inclusion criteria: inclusion criteria:

 Established Diagnosis of Hemolysis

 Sickle Cell Disease (e.g., HbSS, HbS/β-thalassemia, HbSC)

 Other conditions with hemolysis (e.g., RBC membranopathies, enzymopathies, unstable hemoglobinopathies, PNH)

 Age

 SCD participants: 5 years of age up to 19th birthday

 All other participants: 5 years of age and up (no age limit)

Exclusion criteria: :

 Previous cardiac surgery

 Known left ventricle dysfunction (i.e. shortening fraction < 28%)

 Known right sided congenital heart defect such as atrial septal defect or pulmonary valve stenosis

['Clinical Evaluations', 'Laboratory Studies']

['Sickle Cell Disease', 'Hemolytic Anemia']


Evaluation of Residual Urine After Intermittent Catheterisation

Summary: Intermittent catheterization is a well-known method used for emptying the bladder. The objective of this study is to compare the residual urine after intermittent catheterisation with 2 different, hydrophilic coated, intermittent catheters. The study is a randomized, single blinded, crossover study including 24 healthy males.
Inclusion criteria: inclusion criteria:

 Male

 18 years and above

 A negative urine dip-stick

 Have signed informed written consent to participate

Exclusion criteria: :

 The test participant has previous or current congenital deformity, diseases or operation in the lower urinary tract

['Intermittent catheter', 'Compact intermittent catheter']

Intermittent catheter
Compact intermittent catheter


The Effect of Periarticular Multi-Drug Regimen on Pain After Partial Hip Replacement

Summary: This prospective randomized study aims to evaluate the effectiveness of periarticular multi-drug regimen injection on the relief of pain in patients undergoing partial hip replacement.~Total 258 patients will be randomized into one of two groups (groupC or groupI) based on Excel number generation.~Patients in group C will receive no medication intraoperatively, and patients in group I will receive oral oxycodone and celecoxib preoperatively and a periarticular injection of multi-drug regimen during operation.~Visual analogue scale pain scores, fentanyl consumption and the frequency at which patients pushed the button (FPB) of a patient-controlled analgesia system will be recorded at 1, 4, 7 postoperative day.
Inclusion criteria: inclusion criteria:

 femoral neck fracture

 partial hip replacement

Exclusion criteria: :

 r/o infection

 reoperation

 mental change

['periarticular injection of multidrug regimen', 'none of medication preoperatively and intraoperatively']


Study of Brain Blood Flow During Induced Hypercapnia (Excess Blood Carbon Dioxide)

Summary: This study will evaluate magnetic resonance imaging (MRI ) methods for measuring changes in the brain's blood flow during hypercapnia (a condition of excess carbon dioxide in the blood). MRI is a diagnostic tool that uses a large magnet and radio waves to produce images of the body without X-rays.~Healthy normal volunteers in this study may have as many as six MRI scans over a 2-year period. For this procedure, the person lies on a stretcher placed in a strong magnetic field produced by the MRI machine. During the scan, the person's blood carbon dioxide (CO2 ) levels will be increased either by: 1) breathing air mixtures containing up to 5% CO2; or 2) receiving an intravenous (I.V.) injection of a drug called acetazolamide.~Persons who breathe CO2 will have their heart rate, blood pressure and oxygen levels monitored throughout the procedure. Those receiving acetazolamide will have the drug injected intravenously (I.V.) into an arm vein. If the volunteer experiences any unpleasant side effects from the CO2 or acetazolamide, the study will be stopped.~The information gained from this study will be used to develop better ways to study brain function, possibly leading to better diagnostic and treatment methods.
Inclusion criteria: inclusion criteria:

 Any normal volunteer above the age of 18 years old who is capable of giving informed consent.

Exclusion criteria: :

 Subjects will be excluded if they have contraindications to MR scanning, such as the following: aneurism clip, implanted neural stimulator, implanted cardiac pacemaker or autodefibrillator, chochlear implant, ocular foreign body (e.g., metal shavings), or insulin pump. Also, subjects will be excluded if they have panic disorder or migrane (because of possible complications with CO2 inhilation), or if they have cirrhosis, are on high dose aspirin therapy, or have an allergy to acetazolamide injection). Subjects will be excluded if they have allergies to sulfonamide drugs or if they have a chronic respiratory illness.


Effect of Topic Pirfenidone in Diabetic Ulcers

Summary: Pirfenidone is a synthetic molecule, which acts as a potent modulator of the effect of various cytokines (TNF-α, transforming growth factor-β, platelet derived growth factor and vascular endothelial growth factor, among others) that possesses anti-inflammatory and anti-fibrinolytic properties.~The aim of this study is to compare the effect of topic treatment with pirfenidone compared to conventional treatment in chronic diabetic foot ulcers.~The hypothesis is that treatment with topic pirfenidone in chronic diabetic foot ulcers (Wagner 1 to 2) reduces the ulcer size and shortens the healing time compared to conventional treatment. This is a randomized, controlled and crossover study. Patients will be randomly assigned to conventional treatment or topic pirfenidone for eight weeks. At the end of this period they will change groups. Each week ulcers will be for size, depth, length and evidence of infection. The ulcers will have proper debridement in the conventional treatment group and debridement plus topical pirfenidone application in the pirfenidone group. Subjects will be instructed to do daily ulcer cleansing and for those in the topical pirfenidone group, in addition to cleansing they will be instructed to apply the gel twice a day.
Inclusion criteria: inclusion criteria:

 Men or women

 Type 1 or 2 diabetes

 Age ≥ 18 years

 Wagner 1 or 2 diabetic foot ulcer

 Diabetic ulcer for more than 8 weeks duration

 Willing to participate in the study with signed informed consent

Exclusion criteria: :

 Ankle/brachial index < 0.4 (critic ischemia)

 Use topical or systemic antibiotics

 Inability to attend to the weekly evaluations

 Inability to do daily ulcer cleansing

 Autoimmune diseases

 Active pharmacologic topical or systemic ulcer treatment

 Treatment with immunosuppressors such as steroids, radiotherapy, chemotherapy

 Pregnancy or lactation


Study of Percutaneous Renal Artery Intervention for Patient With Heart Failure

Summary: This study will address the role of percutaneous renal intervention for a hemodynamically significant renal artery stenosis in patients with heart failure exacerbations. Current guidelines suggest evaluation for renal artery stenosis in patients with pulmonary edema or heart failure that cannot be attributed to poor left ventricular function. While case series have suggested benefit to percutaneous intervention in patients with heart failure, no randomized study has addressed the potential benefit of renal stenting for heart failure patients. Two large randomized trial of renal stenting for hypertension or poor kidney function failed to show benefit in patients with intermediate renal artery lesions. No evaluation of the potential hemodynamic significance of the lesions was performed prior to randomization. The investigators will enroll patients with heart failure exacerbations not attributable to declining left ventricular function, valvular disease, acute coronary syndrome, or heart transplant rejection, who on non-invasive imaging appear to have renal artery stenosis. After routine invasive assessment, including renal angiography and pressure-wire assessment, patients with hemodynamically significant renal artery stenoses will be randomized to stent implantation or medical therapy. Patients will then be followed to determine whether stenting impacts cardiac mortality or hospitalization for heart failure.
Inclusion criteria: inclusion criteria:

 Men and women age 18 or older referred for invasive evaluation of possible renal artery stenosis will be screened for enrollment.

 Patients must be inpatients admitted for heart failure exacerbation, or have been admitted to a hospital for heart failure exacerbation within the past 90 days. Heart failure is defined as physician documentation or report of any of the following clinical symptoms of heart failure described as dyspnea on exertion, dyspnea occurring in the supine position, fluid retention; or the description of rales, jugular venous distension, pulmonary edema on physical exam, or pulmonary edema on chest x-ray; without being clearly attributable to liver, kidney, or lung disease. Patients must have one of the following: 1. an ejection fraction of 50%; 2. an ejection fraction of 25-50% in the setting of a systolic blood pressure of at least 160 mmHg; or 3. an ejection fraction of 25-50% and a systolic blood pressure of at least 140 mmHg while being treated with at least 2 antihypertensive medications. Patients who meet these criteria and have a proven hemodynamically significant renal artery stenosis (as described in the procedure section) will be included

Exclusion criteria: :

 Patients with heart failure from structural heart disease (including greater than moderate dysfunction of the mitral or aortic valve), acute coronary syndrome, post-partum cardiomyopathy, or acute rejection of a transplanted heart will be excluded. Patients who are considered unlikely to survive to hospital discharge will be excluded. Patients with fibromuscular dysplasia, prior renal stenting, or anatomy unsuitable for renal stenting (i.e. prior vascular surgery making stent delivery impossible) will be excluded. Patients who are unable to take aspirin and clopidogrel will be excluded. Patients with a creatinine clearance <30 mL/min or a history of renal transplantation will be excluded. Pregnant women will be excluded.

 -


Evaluation of Predictive Risk Factors of Chemotherapy-induced Nausea and Vomiting

Summary: The most common toxicity of chemotherapy is nausea and vomiting, and appropriate management of these toxicities can help patients improve tolerance for chemotherapy. Anti-emetics including dopamine antagonist, serotonin antagonist, and substance P antagonist administered to patients according to emetogenic risk of chemotherapeutic drugs. However, patients don't always experience same nausea and vomiting for the same drugs. Therefore, it is important to determine the biomarker to predict chemotherapy-induced nausea and vomiting. Some biomarkers studies were done during the chemotherapy. However it is not definite evidence of relations between biomarkers and chemotherapy. We will hope to find any predictive biomarker of CINV.
Inclusion criteria: inclusion criteria:

 Minimum age of 18 years

 Histologically proven solid organ cancer

 Eastern Cooperative Oncology Group Performance status 0-2

 More than 3 months for life expectancy

 Patients scheduled to receive the first line, first cycle FOLFOX (5-FU, Oxaliplatin, Leucovorin) or FOLFIRI (5-FU, Irinotecan, Leucovorin) chemotherapy

 Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital

Exclusion criteria: :

 Patients who have nausea and vomiting caused by other reasons such as CNS metastases or gastrointestinal obstruction

 Patients who were exposed previously to any chemotherapy except adjuvant FL (5-FU and leucovorin)

 Patients who take anti-emetic drugs or dopamine antagonist within 72 hours prior to administration of chemotherapy

 Patients who take other drugs that may affect serum level of biomarkers (ex. steroid, megesterol, hormone replacement therapy, parenteral nutrition)

['Chemotherapy-induced Nausea and Vomiting']


Factors Affecting the Incidence of Postoperative Delirium in Frail Elderly

Summary: Postoperative delirium has been found to be associated with increased risk of future neurocognitive decline and mortality especially in elderly patients. Similarly, Frailty has been found to be associated with an increased risk of postoperative complication including delirium in the elderly.The purpose of this study is determine the factors affecting the incidence of postoperative delirium in frail elderly undergoing non-cardiac surgery in the Singapore population.
Inclusion criteria: inclusion criteria:

 Elderly (> 65 years) frail patients undergoing non cardiac surgery under anaesthesia lasting for >60 minutes

 Patient willing and able to complete the requirements of this study.

Exclusion criteria: :

 disabling neuropsychiatric or neurological disorders(including severe dementia, Alzheimer's disease, schizophrenia, severe depression)

 patients suffering from delirium at selection;

 patients who cannot complete the preoperative mental tests (CAM and/or Mini-Mental State Examination (MMSE)) of this clinical trial;


Steroids in the Maintenance of Remission of Proliferative Lupus Nephritis

Summary: There is debate as to whether long-term low-dose steroids such as prednisolone help to suppress relapses of systemic lupus erythematosus (SLE) in patients who are in remission from their lupus nephritis. If low-dose prednisolone reduces relapses, these beneficial effects may be counter-balanced by the long-term side-effects associated with prednisolone. This pilot study will determine the feasibility of conducting a larger randomized control trial that will answer the question of whether or not long-term low-dose prednisolone (5 - 7.5 mg/day) reduces the flares of SLE in patients with previous lupus nephritis.
Inclusion criteria: inclusion criteria:

 age at least 18 years

 diagnosis of SLE by ACR criteria

 diagnosis of proliferative lupus nephritis (ISN/RPS class III or IV)

 currently on prednisolone (5 to 20 mg/day)

 in partial or complete remission for at least 3 months

Exclusion criteria: :

 currently pregnant

 in end-stage renal failure

 receiving corticosteroids for an indication other than lupus nephritis


Zambia Micronutrient Powder Trial Effectiveness Study

Summary: Addressing micronutrient deficiencies in Zambia is recognized as a national priority by the government due to its major contribution to morbidity and mortality among children, especially infants in their formative years. One of the most successful, cost-effective, and recommended strategy to address micronutrient malnutrition is 'in-home fortification' with micronutrient powders (Sprinkles being the most widely recognized) along with nutrition education. While this intervention has proven to be safe, effective, and efficacious in numerous other countries, a specific national protocol must be developed to maximize its effect on reducing anaemia in Zambian children. The proposed research aims to inform such protocol.
Inclusion criteria: inclusion criteria:

 Aged 6-11

 Residing within the project catchment area, and plan on remaining in the same household for the 12 month study duration

 Parent/guardian willingness to give consent for the child's participation in the study

Exclusion criteria: :

 Weight-for-height Z score <3 SD

 Mid-upper arm circumference < 11.5 cm

 Presence of bilateral oedema

 Severe anaemia (Hb < 7.0 g/dl)

 HIV positive


New Markers to Measure Clotting in Patients With the Obstructive Sleep Apnoea Hypopnoea Syndrome

Summary: Obstructive Sleep Apnoea Hypopnoea Syndrome(OSAHS)affects at least 4% of males and 2% of females.~OSAHS is the combination of excessive daytime sleepiness, snoring and apnoeas (stopping breathing at night). As well as affecting tiredness, mood, concentration and quality of life - there is growing concern that it can increase the risk of high blood pressure, heart problems, strokes and thromboses (clots in the veins).~It appears that OSAHS may affect the thickness of the blood and cause it to clot more easily it also causes damage to the lining of the blood vessels (endothelial injury). These effects seem independent of other risk factors such as obesity, smoking, family history of clots etc.~The investigators are testing new biomarkers: gel point and fractal dimension developed at the Swansea University to measure the 'clotting' of the blood in people with OSAHS and a similar group of people who snore and who are sleepy but do not have OSAHS on sleep studies (Controls) Also markers of vascular inflammation are being measured.
Inclusion criteria: inclusion criteria:

 18-80 year old with h/o daytime sleepiness, snoring and apnoeas

Exclusion criteria: :

 Refusal to give written informed consent.

 Personal or family history of pro- thrombotic or bleeding disorders, severe liver disease (clotting problems) and those prescribed warfarin or heparin.

 Those with borderline sleep studies (4% Diprate or AHI 10-14 per hour).

 Aged less than 18 years or greater than 80 years.

['Obstructive Sleep Apnoea Hypopnoea Syndrome', 'Biomarkers of Fibrin Clot Structure', 'Biomarkers of Vascular Endothelial Injury']


Cost of Care for Juvenile Idiopathic Arthritis

Summary: This project seeks to collect data on healthcare utilization and expenditure rates in Juvenile Idiopathic Arthritis (JIA) patients from across the US, correlate these costs with disease activity and outcome measures and determine methods by which to reduce the economic impact while improving outcomes.
Inclusion criteria: inclusion criteria:

 Subject has been diagnosed with JIA by a pediatric rheumatologist according to published criteria.

 Person providing consent must be able to read English.

 Subject (and/or parent/legal guardian) is able to provide informed consent and willing to comply with study procedures.

Exclusion criteria: :

 Subject/ legal guardian is unwilling to provide consent, cannot read English, or does not meet published criteria for JIA.

 Coexisting rheumatologic disorder

 Diagnosis of fibromyalgia

 Participation in a drug trial in the past 6 months.


REalWorld Insights on the INitiation and Treatment Duration of ticagrEloR & Other Oral Antiplatelets (OAP) in Patients With Acute Coronary Syndrome (ACS) in Be/Lux.

Summary: REWINDER is a multinational, multicentre, non-interventional, retrospective study of patients treated with an oral antiplatelet (ticagrelor, prasugrel or clopidogrel) while in hospital after an acute coronary syndrome (ACS) event, to be conducted in Belgium and Luxembourg.~Primary objective is to evaluate the actual treatment persistence with oral antiplatelets (OAP) after an ACS in the clinical practice in Belgium and Luxembourg.~The main secondary objectives are to describe the most frequent reasons for OAP treatment switch, discontinuation or reinitiation; to identify the decisionmakers in the OAP treatment changes and to characterize the patient profile in terms of demographics, diagnosis, management strategies, comorbidities and concomitant medications to identify any association between patient profile and treatment duration.
Inclusion criteria: inclusion criteria:

 The patient population that will be observed in the NIS must fulfil all of the following criteria:

 Female or male aged ≥18 years

 A patient information letter has been sent by the Investigator to the patient

 Patient discharged alive from this hospital to home following ACS (diagnosed with STEMI, NSTEMI or UA)

 ACS is either UA or myocardial infarction of Type 1 (spontaneous myocardial infarction related to ischemia due to a primary coronary event such as plaque erosion and/or rupture, fissuring, or dissection)

 ACS after 1st July 2012 and before 1st June 2013

 Patient on ticagrelor, prasugrel or clopidogrel treatment at discharge following an ACS

Exclusion criteria: :

 Patients will not be eligible to participate if any of the following

['Treatment of Acute Coronary Syndrome (ACS).']


The Effects of RPL554 on Top of Standard COPD Reliever Medications

Summary: This study evaluates the addition of RPL554 to standard reliever medications for chronic obstructive pulmonary disorder (COPD). All patients will receive the same six treatments in a randomised sequence:~salbutamol,~ipratropium,~salbutamol + RPL554,~ipratropium + RPL554,~RPL554~Placebo
Inclusion criteria: inclusion criteria:

 Provide informed consent

 Males not donating sperm and using adequate contraception or females who are surgically sterile or postmenopausal

 12-lead ECG showing:Heart rate 45 to 90 bpm, QTcF≤450 msec, QRS ≤120 msec, PR interval ≤220 msec, no clinically significant abnormality

 Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.

 BMI 18 to 33 kg/m2 with a minimum weight of 45 kg.

 COPD diagnosis for at least 1 year and clinically stable COPD in previous 4 weeks

 Demonstrates reversibility to bronchodilator (two puffs of salbutamol followed by two puffs of ipratropium) via spirometry:

 Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70

 Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal

 ≥150 mL increase from pre-bronchodilator FEV1

 Chest X-ray showing no abnormalities

 Meet the concomitant medication restrictions and be expected to do so for the rest of the study.

 Smoking history of ≥10 pack years.

 Capable of withdrawing from long acting bronchodilators throughout the study and short acting bronchodilators for 8 hours prior to study treatment.

Exclusion criteria: :

 History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.

 COPD exacerbation requiring oral steroids in the previous 3 months

 History of one or more hospitalisations for COPD in the previous 12 months

 Respiratory tract infection (both upper and lower) treated with antibiotics in previous 12 weeks

 Evidence of cor pulmonale or clinically significant pulmonary hypertension.

 Other respiratory disorders

 Previous lung resection or lung reduction surgery.

 Oral therapies for COPD in the previous 3 months and throughout the study.

 Drug or alcohol abuse in the past 3 years

 Received an experimental drug within 3 months or five half lives, whichever is longer.

 Prior exposure to RPL554

 Patients with a history of chronic uncontrolled disease that the Investigator believes are clinically significant.

 Documented cardiovascular disease in last 3 months

 Major surgery, (requiring general anaesthesia) in the previous 6 weeks, or will not have fully recovered from surgery, or planned surgery through the end of the study.

 History of malignancy of any organ system within 5 years with the exception of localised skin cancers (basal or squamous cell)

 Clinically significant abnormal values for safety laboratory tests

 A disclosed history, or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.

 Requires oxygen therapy, even on an occasional basis.

 Inability to adequately perform whole body plethysmography.

 Any other reason that the Investigator considers makes the subject unsuitable to participate.

 Patients with known hypersensitivity to atropine or its derivatives, or to ipratropium bromide, salbutamol or RPL554 or their excipients/components.

['Salbutamol', 'Ipratropium', 'RPL554', 'Salbutamol matched placebo', 'Ipratropium matched placebo', 'RPL554 matched placebo']

Salbutamol
Ipratropium
RPL554
Salbutamol matched placebo
Ipratropium matched placebo
RPL554 matched placebo

['Chronic Obstructive Pulmonary Disease']


A Global Active Surveillance for Community Acquired Pneumonia

Summary: This study is an observational surveillance study to identify adults 50 years and older who present to a study healthcare facility with signs and symptoms of Community-Acquired Pneumonia.
Inclusion criteria: inclusion criteria:

 Adult subjects 50 years of age or older

 Subject must reside in the surveillance area

 Subjects who present to a study healthcare facility where the treating physician clinically suspects CAP

Exclusion criteria: :

 Any subject who is transferred to a study healthcare facility after already being hospitalized for 48 hours or more at any other in-patient facility (such as a community hospital).

 Hospital Acquired pneumonia (ie, develops signs and symptoms of pneumonia after being hospitalized for 48 hours or more).

['Blood draw', 'Chest X-ray', 'urine specimen', 'Nasopharyngeal swab', 'sputum']

Blood draw
Chest X-ray
urine specimen
Nasopharyngeal swab
sputum


Dislocated Unstable Distal Both-Bone Forearm Fractures in Children

Summary: We create a follow-up study of Kirschner wire fixation of a unstable dislocated distal both-bone forearm fracture.
Inclusion criteria: inclusion criteria:

 both-bone forearm fracture

 distal

 dislocated

 unstable after reposition

 age < 16 years

Exclusion criteria: :

 fracture older than 1 week

 no informed consent

 refracture

 open fracture (Gustillo 2 and 3)

 both fractures of type torus

['Fracture', 'Forearm', 'Distal', 'Child', 'Treatment']


Efficacy and Safety Study of Loperamide Hydrochloride/Simethicone Chewable Tablet in Treatment of Acute Diarrhea With Abdominal Discomfort and Flatulence

Summary: The purpose of this study is to evaluate the efficacy and safety of combined loperamide hydrochloride and simethicone compared to loperamide hydrochloride monotherapy in treating acute diarrhea associated with abdominal discomfort caused by gastrointestinal gas accumulation.
Inclusion criteria: inclusion criteria:

 Participant's symptoms of acute diarrhea must manifest within 48 hours prior to entering the trial

 Participant must have experienced at least three incidences of unformed stool within 24 hours prior to entering the trial (referring to any instances of watery stool or soft stool as determined after placing the stool in a container)

 Participant's most recently produced stool must be unformed stool

 Participant must give a positive answer to the following question: Have you felt any abdominal discomfort caused by gastrointestinal gas accumulation within the last hour

 Female participants must take effective contraceptive measures throughout the trial (including oral or injectable contraceptives, contraceptive tools, ligation) or be postmenopausal

Exclusion criteria: :

 Participant hospitalized for treatment of severe acute diarrhea or otherwise requires intravenous fluids or antibiotics on an outpatient basis

 Participant shows an axillary temperature greater than (>) 38.2 degrees Celsius (C) or an oral temperature > 38.6 degrees C

 Participant shows clinical symptoms of bloody or purulent stool or erythrocytes or leukocytes are detected in the participant's stool at > 3 per high power field

 Participant shows a sitting systolic blood pressure less than (<) 90 millimeter of mercury (mmHg) and/ or diastolic blood pressure < 60 mmHg

 Participant is unable to take medication orally or tolerate oral rehydration

['Loperamide hydrochloride + simethicone chewable tablet', 'Loperamide hydrochloride', 'Loperamide hydrochloride + simethicone chewable placebo tablet', 'Loperamide hydrochloride placebo capsule']


Compliance and Persistence With Osteoporosis Treatment and Attitude Towards Future Therapy Among Post-menopausal Israeli Women During Drug Treatment or Drug Holiday

Summary: The purpose of the study is to provide information about the rate of response and persistence to drug therapies for osteoporosis. Another issue examined in this study refers to the preferences and concerns about future treatments in patients during drug holiday.
Inclusion criteria: inclusion criteria:

 Postmenopausal women

 Diagnosis of osteoporosis in the medical record

 At least one prescription drug to treat osteoporosis in the last 5 years

 Insured by Clalit Health Services

 Hebrew-speaking capability and readiness to answer a questionnaire

Exclusion criteria: :

 Premenopausal women

 No diagnosis of osteoporosis in the medical record

 No treatment for osteoporosis in the last 5 years

 Women who do not speak Hebrew or are unable to answer a questionnaire

['Questionnaires about compliance and persistence with bisphosphonates treatment']


Fed Bioequivalence Study of Zolpidem Tartrate Tablets and Ambien® Tablets

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

 Sex: Male or Female; similar proportions of each preferred

 Age: At least 18 years

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

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

 Subjects must read and sign the Consent Form

Exclusion criteria: :

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

 history of malignancy, stroke, diabetes, cardiac, renal or liver disease

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

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

 history of mental depression, pulmonary disease, sleep apnea

 females who are pregnant or lactating

 history of hypersensitivity to zolpidem tartrate, or any hypnotic or sedative

 conditions upon screening which might contraindicate or require that caution be used in the administration of zolpidem tartrate, including sitting systolic blood pressure below 90 mm Hg, or diastolic pressure below 50 mm Hg; heart rate less than 50 beats per minute after a 5-minute rest in a seated position

 inability to read and/or sign the consent form

 treatment with any other investigation drug during the four (4) weeks prior to the initial dosing for this study

 subjects who have donated blood within four (4) weeks prior to the initial dosing for this study

 subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.) Three (3) months abstinence is required.

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


Assess the Effect of Zolpidem, Silenor & Placebo on Arousability, Ataxia/Balance & Cognition in Healthy Volunteers

Summary: This is a Phase IV, randomized, double-blind, placebo-controlled, four-arm crossover study. The study will assess the effects of a single dose of Silenor 6 mg compared with matching placebo and a single dose of zolpidem 10 mg compared to its matching placebo at the respective T-max in normal healthy adult male volunteers. The study will be conducted in approximately 52 male subjects
Inclusion criteria: inclusion criteria:

 Be in good general health as determined by the investigator;

 Have a 3-month history of a normal nightly sleep pattern based on the subject's self report ;

 A usual time in bed

 A regular bedtime between 2200 and 2400 hours

 No habitual daytime napping;

 Epworth Sleepiness Scale score ≤ 10;

 Be able to read, understand, and provide written/dated informed consent before enrolling in the study, and must be willing and able to comply with all study procedures;

 Be able to follow verbal and written instructions provided in English

Exclusion criteria: :

 Have a body mass index (BMI) >35 kg/m2

 Have symptoms consistent with the diagnosis of any sleep disorder (e.g., insomnia, sleep apnea, narcolepsy, periodic leg movements, or restless leg syndrome);

 On screening PSG AHI > 10 or PLMAI >10;

 Have a known or suspected diagnosis of Acquired Immune Deficiency Syndrome (AIDS), or have tested seropositive for human immunodeficiency virus (HIV) antibody or antigen previously;

 Have any clinically significant abnormal finding in physical examination, neurological assessment, vital signs, elevated body temperature, or clinical laboratory tests, as determined by the Investigator;

 Have a known exaggerated pharmacological sensitivity, hypersensitivity, or history of a clinically significant adverse reaction to zolpidem;

 Have a known or exaggerated pharmacological sensitivity, hypersensitivity, or intolerance to doxepin HCl, any tricyclic antidepressant, or antihistamine;

 Currently taking cimetidine or a monoamine oxidase inhibitor (MAOI);

 Current diagnosis of severe urinary retention;

 Current diagnosis of untreated glaucoma;

 Intends to use any medication including over-the-counter (OTC) medications that would interfere with normal sleep architecture (such as systemic steroids, beta-adrenergic blockers, amphetamines, modafinil, etc.);

 Self-reports use of products containing nicotine of greater than 15 cigarettes daily, or cannot avoid products containing nicotine during the normal sleep periods;

 Self report consumption of more than five alcoholic beverages on any one day or greater than 14 alcoholic beverages weekly over the past week;

 Have a history of epilepsy or serious head injury;

 Used CYP450 2D6 inducers or inhibitors within 7 days before screening;

 Have used prescribed or OTC medications within 30 days of screening (Day 0) or intend to use any prescription or OTC medication during the study that may interfere with the evaluation of the study drug.

 Have used an investigational drug within 30 days or five half lives (whichever is longer) before screening, or plans to use an investigational drug during the study or have used doxepin or zolpidem previously.

 Score of < 40 on the BBS at screening

['Silenor 6 mg', 'zolpidem 10 mg', 'Placebo', 'Placebo']

Silenor 6 mg
zolpidem 10 mg
Placebo
Placebo


The Role of Heart Stiff and Weak Atrium on Exercise Capacity in Patients With Hypertrophic Cardiomyopathy

Summary: This study will examine how heart stiffness and a weak atrium affect exercise capacity and symptoms in patients with hypertrophic cardiomyopathy (HCM). The atrium is the booster pumping chamber of the heart that helps the ventricle (main pumping chamber), to fill properly. HCM is an inherited disease in which the ventricle becomes thickened and, in some patients, stiff. The stiffness makes it difficult for the ventricle to fill and empty, causing breathing difficulty, fatigue, and reduced exercise capacity. Scar formation and a weakened atrium can cause the heart to stiffen. Information gained from this study may guide doctors in prescribing medicines to reduce scarring or improve atrial function.~Patients 21 years of age and older with hypertrophic cardiomyopathy may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram (EKG), blood tests, Holter monitor, and echocardiogram. A Holter monitor is a device about the size of a Walkman that is connected to three wires that are attached to the chest. It is worn for 24 hours to provide continuous monitoring of heart rhythm. An echocardiogram uses a small probe that emits sound waves to produce images of the heart. The probe is moved across the chest and the reflection of the sound waves from the chambers of the heart produce images showing the heart's thickness and function.~Participants will undergo the following tests and procedures over 3 days:~Physical examination and echocardiogram.~Intravenous cannula insertion: A plastic tube is inserted into an arm vein for collecting blood samples to measure substances that the heart and circulatory system release at rest and during exercise.~Impedance cardiography: A small current of electricity is passed across the chest and electrodes similar to those used for an EKG test are placed to measure blood flow in the area of the current.~Pulmonary artery catheterization: A catheter (plastic tube) is inserted into a vein either in the arm, under the collarbone, or in the neck and advanced to the right atrium and ventricle. The catheter remains in place during the echocardiogram tilt and bicycle exercise tests (see below).~Echocardiogram tilt test: The patient lies flat on a table. After a few minutes, the table is tilted so that the patient's head is just above his or her feet for a short while, then is positioned flat again, and then tilted so the feet are just above the head. Echocardiographic measurements and blood samples are taken at intervals to examine heart function during changes in posture.~Echocardiogram bicycle stress test: The patient exercises for as long as possible on a bicycle-like machine while lying on his or her back. Echocardiographic measurements and blood samples are taken at intervals during the test.~Treadmill stress test: The patient runs for as long as possible on a treadmill that increases in difficulty. The patient wears a facemask or mouthpiece through which small amounts of gases are added in order to measure the ability of the heart and lung to increase their effectiveness with exercise.~Digoxin loading: Only patients who demonstrate limited exercise capacity and for whom digoxin is not a risk will undergo this procedure. A medicine that makes the heart contract more strongly, digoxin is used to treat certain heart abnormalities. Patients are given doses of either digoxin or placebo (a look-alike injection with no active ingredient) at 4-hour intervals over a 24-hour period and then repeat the tilt test and the bicycle and treadmill exercise tests
Inclusion criteria: inclusion criteria - HCM Patients:

 HCM defined as maximal LV wall thickness by echocardiography greater than 13mm in the absence of other causes of LVH or greater than 15mm asymmetrical LV wall thickness if there is a history of mild hypertension (defined as systolic less than 160mmHg and diastolic less than 100mHg) controlled for greater than 6 months

 Non-obstructive HCM

 Age greater than or equal to 21 years.

 Patients with LV obstruction treated by LV myotomy and myectomy or percutaneous septal alcohol ablation that meet inclusion criteria are eligible for this study.

Exclusion criteria:  - HCM Patients:

 LV outflow obstruction noted during Doppler echocardiography at rest or with Valsalva maneuver defined as instantaneous peak gradient greater than 30 mmHg

 Hemodynamically significant valvular disorders, history of significant coronary obstruction (greater than 50% in any single artery), angina symptoms, myocardial ischemia on an imaging stress test or evidence of prior myocardial infarction. Patients older than 40 years of age with effort induced anginal symptoms typical of coronary insufficiency and a coronary distribution of myocardial ischemia on an imaging stress test will be considered for the study if coronary angiography rules out significant obstructive coronary disease.

 Chronic atrial fibrillation

 Cardiac pacemaker or other metallic implant unsafe for MRI

 Uncontrolled hypertension

 Dependence on a beta blocker that cannot be withdrawn

 Dependence on a calcium blocker that cannot be withdrawn

 Current use of digoxin

 History of digitalis intolerance

 Renal failure

 Diabetes mellitus

 Pregnancy or lactation

 Failure to indicate effective method of birth control measures if female patient is of childbearing age.

 Inability to exercise or disease states likely to result in impaired exercise capacity (such as pulmonary, hematological and musculoskeletal disorders)

 Echocardiographic images of insufficient quality, even after administration of contrast agent, for volumetric analysis.

 Inability to provide informed consent


What Needle Diameter Should Physician Use When They Perform Lumbar Puncture ? A Randomized Controlled Trial

Summary: This study is intended to help guide the choice of needle diameter when performing a lumbar puncture.~Smaller spinal needles have been shown to decrease rate of adverse events such as post-lumbar puncture headache and hearing loss.~The main drawback to using smaller needles is diminished flow rate; some textbooks recommend using needles no smaller than 22 gauge because of the slow flow rate though others recommend smaller needles, namely 22-24 gauge.~Some authors have described a successful use of spinal needles as small as 25 gauge when performing a lumbar puncture.~The investigators do not believe that the flow-rate difference between 22 and 24 gauge needles is significant enough to justify using the larger needles.~The investigators trial will compare the Whitacre 22 gauge and Whitacre 24 gauge needles for flow rate, and incidence of the known complications of pain during procedure and backache at 8 and 15 days post-procedure.~The investigators will also look at whether smaller needles are associated with less pain during the procedure and less backache the next 2 weeks after the procedure.
Inclusion criteria: inclusion criteria:

 All adult patients (>= 18 years old) referred at the Neurological Day Center to get a lumbar puncture

Exclusion criteria: :

 Contraindication to get a lumbar puncture

['whitacre 24 gauge', 'whitacre 22 gauge']

['Post-lumbar Puncture Headache', 'Backache']


Regional Fat Depots and Insulin Resistance

Summary: The biological basis for insulin resistance associated with obesity is unknown. By studying equally-overweight/obese individuals who are either insulin resistant or insulin sensitive, the investigators will compare characteristics of fat tissue to test several hypotheses: 1) impaired differentiation and fat storage in the subcutaneous fat depot characterize insulin resistant individuals, who have, as a result, fat in other tissues like liver and muscle, as well as more fat circulating in the blood; 2) inflammation is greater in visceral and/or subcutaneous adipose tissue depots in insulin resistant individuals as compared with insulin sensitive individuals.
Inclusion criteria: inclusion criteria:

 No major organ disease

 Fasting blood glucose < 126 mg/dL

 BMI 25-35 kg/m2

 Nonpregnant/nonlactating

Exclusion criteria: :

 pregnancy/lactation

 major organ disease

 drugs that influence insulin resistance

 unstable body weight or active weight loss program

 outside BMI range or age range

 diabetic by fasting glucose criteria 126 mg/dL or higher

['Obesity', 'Insulin Resistance', 'Diabetes Mellitus Type 2']

Obesity
Insulin Resistance
Diabetes Mellitus Type 2


A Study on Assessment of STELARA and Tumor Necrosis Factor Alpha Inhibitor Therapies in Participants With Psoriatic Arthritis

Summary: The purpose of this study is to evaluate treatment retention in psoriatic arthritis participants with STELARA or tumor necrosis factor alpha inhibitor (TNFi) therapies in relation to effectiveness, safety, benefit/risk and to examine clinical response.
Inclusion criteria: inclusion criteria:

 Must have a confirmed diagnosis of psoriatic arthritis (PsA) as determined by a rheumatologist according to ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria

 Must be starting either STELARA or any new approved tumor necrosis factor alpha inhibitor (TNFi) (including TNFi biosimilar) as a new biologic disease-modifying antirheumatic drug (bDMARD) therapy in a first, second or third line of bDMARD therapy for PsA at the time of enrollment into the observational study or within a maximum 2-month window after the baseline visit

 Must sign a participation agreement/informed consent form (ICF) allowing data collection and source data verification in accordance with local requirements

Exclusion criteria: :

 Participant is starting STELARA or a TNFi therapy as fourth or further line of biologic treatment

 Participant is unwilling or unable to participate in long-term data collection

 Participant has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 30 days before the start of the study or the first data collection time point

 Participant is currently enrolled in an interventional study


Investigation on the Role of Corticosteroids and Beta-Agonists on Cytokine Production in COPD Patients

Summary: Research on the synergistic effect of corticosteroids and beta-agonists on the cytokine production in COPD patients. Blood will be obtained from healthy volunteers and COPD patients and blood monocytes will be stimulated to produce cytokines with or without the prementioned drugs.
Inclusion criteria: inclusion criteria:

 clinical COPD

 smoking

 age > 40 years

Exclusion criteria: :

 age < 40 years

 use of antibiotics, corticosteroids or beta-agonists


Voriconazole for IPA in Chinese Patients With COPD

Summary: voriconazole is recommended as first-line therapy for invasive pulmonary aspergillosis, however the efficacy and safety of voriconazole for treating invasive pulmonary aspergillosis secondary to COPD is not clear. This study aims to investigate the effectiveness and tolerability of intravenous voriconazole for treatment of invasive pulmonary aspergillosis in Chinese patients with COPD, by monitoring changes in clinical symptoms, eradication of aspergillus, improvement of chest imaging as well as record of possible adverse reactions following 2-week intravenous instillation of voriconazole.
Inclusion criteria: inclusion criteria:

 Cases of invasive pulmonary aspergillosis secondary to COPD

Exclusion criteria: :

 Use of voriconazole or itraconazole or amphotericin B or caspofungin or micafungin within 4 weeks prior to enrollment

 Known allergy to voriconazole

 Severe impairment of live or kidney function

 Septic shock

 Unwilling to sign informed consent

['Invasive Pulmonary Aspergillosis', 'COPD']


Establishing Visualization Grading Scale on LESS Cholecystectomy

Summary: Essential to laparoscopic operations is adequate visualization. Unfortunately there is no grading system to assess the degree or quality of visualization. The primary objective of the project is to develop a laparoscopic visualization scoring system. We also intend to investigate the effects of neuromuscular blockade agents on visualization.
Inclusion criteria: inclusion criteria:

 Signed informed consent

 18 years of age and older

 All patients deemed to have a clinical and surgical indication to undergo a LESS cholecystectomy

Exclusion criteria: :

 Pregnancy

 Breastfeeding

 BMI>35

 Serious comorbidities precluding a LESS cholecystectomy

 Known or suspected neuromuscular disorders impairing neuromuscular function

 Allergies to muscle relaxants, anesthetics or narcotics utilized for this study

 A (family) history of malignant hyperthermia

 A contraindication for neostigmine administration

 Chronic opioid use

 Prolonged QT syndrome

 Creatinine >2.0


Comparison of Vitamin B12 Supplementation to Selective Serotonin Reuptake Inhibitor (SSRI) Versus SSRI Antidepressant Treatment Alone

Summary: While treating depression, significant numbers respond poorly to anti-depressants; one cause is vitamin B12 deficiency. The investigators are conducting an open label randomized controlled trial to investigate difference in response to SSRI monotherapy alone versus SSRI and intramuscular B12 replacement in people with low-normal B12 levels. 300 participants will be allocated to each arm of intervention at out patient clinics of the department of Psychiatry at Aga Khan University Hospital, Karachi Pakistan. Baseline and 3 month measurement of depression will be on Hamilton Rating Scale for Depression (Urdu version) and response rates compared.
Inclusion criteria: inclusion criteria:

 Adults between ages 18 to 64 years who meet the criteria for a depressive episode as measured by a score of ≥ 16 on first 17 items of HAM-D (Urdu version.

 Patients with low normal B12 levels in serum (>191 but < 300 pg/ml)

 Those who will provide informed consent

Exclusion criteria: :

 Patients with concurrent unstable medical illness

 History of manic episodes or psychotic illness

 Psychotic symptoms within depressive episode


Study to Investigate the Induction of an Protective Immune Response to Malaria

Summary: The objective of the study is to induce a protective immune response against malaria in healthy human volunteers. The different parts of the immune response will then be studied.
Inclusion criteria: inclusion criteria:

 Age > 18 and < 45 years healthy volunteers (males or females).

 General good health based on history and clinical examination.

 All volunteers have to sign the informed consent form.

 Negative pregnancy test.

 Use of adequate contraception for females

 Reachable by phone during the whole study period.

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

Exclusion criteria: :

 History of malaria or residence in malaria endemic areas within the past six months.

 Positive serology for P. falciparum

 Previously participated in any malaria vaccine study

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

 Cardiovascular risk >10% according to European guidelines, taking into account sex, age, cholesterol, weight, smoking habits, blood pressure, diabetes

 Any laboratory abnormalities on screened blood samples beyond the normal range, as defined at UMC St Radboud. Positive HIV, HBV or HCV tests.

 Volunteers should not be enrolled in any other clinical trial during the whole trial period.

 Volunteers should not receive chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the three months preceding the screening visit or during the study period.

 Pregnant or lactating women.

 Volunteers unable to give written informed consent.

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

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

 Known hypersensitivity for anti-malaria drugs

 Volunteers are not allowed to travel to malaria endemic countries during the study period.


Phase I Trial of Inhaled Nitric Oxide to Treat Acute Pulmonary Embolism

Summary: This study will test the hypothesis that patients with acute PE and dyspnea can safely inhale NO. The secondary hypothesis is that patients who are blinded to the inhaled NO concentration will sustain subjective improvement in their perception of dyspnea based upon their reported Borg dyspnea score, during inhalation of NO.~Specific aims~Test if patients with acute PE and shortness of breath of severity ≥ 5 on a 0-10 scale called the Borg score can have inhaled nitric oxide administered via nasal cannula or face mask in a titration protocol that increases concentration by 5 ppm in 5 min steps to a maximum of 25 ppm.~We will measure the number of patients who meet an absolute safety endpoint during titration. An absolute safety endpoint requires execution of a rapid weaning protocol (2 ppm decrease per minute to 0 ppm).~Absolute safety endpoints: Two consecutive SBP measurements more than one min apart with both readings < 80 mm Hg;SaO 2 <80% for more than 15 seconds; Patient deterioration as defined by: Clinical decision for need of inotropic or pressor support for any reason, seizure, new altered mental status, focal neurological signs suggestive of cerebral ischemia, evidence of myocardial ischemia, protracted vomiting.~Test if the patient-reported Borg score decreases with administration of NO. Patients will not be told any details about the timing of the titration and will not be made aware of their iNO concentration when the Borg score is assessed.
Inclusion criteria: inclusion criteria:

 inclusion criteria:

 Diagnosis of acute PE requires symptoms of PE present <14 days with CT angiography interpreted as positive for acute PE. Initial evaluation for PE must be predicated upon the investigation of new or unexplained cardiopulmonary or chest-related clinical features consistent with PE, including shortness of breath, chest pain, respiratory distress, dizziness, unexplained tachypnea, tachycardia, syncope, cough or hemoptysis. All patients must have CT chest angiography with <2 mm collimation,(36) with or without indirect venography. Pulmonary arterial opacification will be achieved with power injection of non-ionic, low osmolar contrast in an antecubital vein with a timing run; the pitch, voltage, gantry speed and other technical details appropriate for each scanner.(37;38) Images will be interpreted as positive for intrapulmonary arterial filling defect consistent with acute PE using our published definitions(37;38) by a board-certified radiologist with specialty training in body CT or emergency medicine imaging in all cases.

 SBP (SBP)> 89 mm Hg at the time of enrollment. We will allow enrollment for a patient with an SBP < 90 mm Hg prior to enrollment, or a patient with a SBP>80 mm Hg, if the patient has a documented or patient-identified history of low blood pressure and has no symptoms of shock, as described by Jones et al.(39)

 SaO2% >80% at time of enrollment.

 Patients must have a Borg score greater than 4/10.

Exclusion criteria: :

 Altered mental status such that they are unable to provide consent.

 Inability to use a nasal cannula or face mask (e.g., anatomic defect)

 Supplemental oxygen requirement greater than can be administered via nasal cannula or face mask in order to maintain SaO2 >80%.

 Pregnancy

 Pneumothorax with decompression

 A serum mtHb greater than 10%

 Concurrent therapies including:

 Viagra® (sildenafil) use within the past 24 hours

 Levitra® (vardenafil) use within the past 24 hours

 Cialis® (tadalafil) use within the past 72 hours

 Use nitroprusside or nitroglycerine with in the past 4 hours

 Concomitant use of pressor or inotropic agents

 Use of fibrinolytic agent with in the past 14 days

 Use of nitrates within the past 24 hours


AdCh63 ME-TRAP and MVA ME-TRAP Malaria Vaccines Evaluation in Healthy Adults and Children in a Malaria Endemic Area

Summary: The purpose of this trial is to assess the safety and immunogenicity of MVA ME-TRAP and AdCH63 ME-TRAP candidate vaccines in healthy children and adult volunteers in a malaria endemic region. The regimen proposed here has protected non-immune volunteers in Oxford against sporozoite challenge, and so may be protective against naturally acquired infection in The Gambia.
Inclusion criteria: inclusion criteria:

 Consenting adult males aged 18-50 years in good health and healthy children aged 2-6 years.with consenting parents.

Exclusion criteria: :

 Clinically significant history of skin disorder (psoriasis, contact dermatitis etc.), allergy, symptomatic immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness.

 Severe malnutrition.

 Hypersensitivity to HDCRV.

 History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, Kathon, neomycin, betapropiolactone.

 History of splenectomy Haemoglobin less than 9.0 g/dL, where judged to be clinically significant in the opinion of the investigator

 Serum Creatinine concentration greater than 70 mol/L, where judged to be clinically significant in the opinion of the investigator

 Serum ALT concentration greater than 45 U/L, where judged to be clinically significant in the opinion of the investigator

 Blood transfusion within one month of enrolment.

 History of vaccination with previous experimental malaria vaccines.

 Administration of any other vaccine or immunoglobulin within two weeks before vaccination.

 Current participation in another clinical trial, or within 12 weeks of this study.

 Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial.

 Likelihood of travel away from the study area.

 HIV positive.

 Positive malaria antigen test

['AdCh63 ME-TRAP, MVA ME-TRAP', 'AdCh63 ME-TRAP, MVA ME-TRAP', 'AdCh63 ME-TRAP, MVA ME-TRAP', 'AdCh63 ME-TRAP, MVA ME-TRAP', 'HDCRV', 'AdCh63 ME-TRAP, MVA ME-TRAP', 'AdCh63 ME-TRAP, MVA ME-TRAP', 'HDCRV']

AdCh63 ME-TRAP
MVA ME-TRAP
AdCh63 ME-TRAP
MVA ME-TRAP
AdCh63 ME-TRAP
MVA ME-TRAP
AdCh63 ME-TRAP
MVA ME-TRAP
HDCRV
AdCh63 ME-TRAP
MVA ME-TRAP
AdCh63 ME-TRAP
MVA ME-TRAP
HDCRV


Safety Study in Volunteers From 16 to 65 Years of Age: FSME IMMUN NEW vs. ENCEPUR

Summary: The purpose of this study is to assess the safety of a vaccination schedule consisting of two vaccinations (21-35 days apart) with the tick-borne encephalitis (TBE) vaccine FSME-IMMUN NEW (5 consecutive lots) in comparison to another licensed TBE vaccine (Encepur® adults, with polygeline) (2 lots) in healthy volunteers aged 16 to 65 years.
Inclusion criteria: inclusion criteria:

 Male and female volunteers were eligible for participation in this study if they:

 Were 16 years (from the 16th birthday) to 65 years (to the last day before the 65th birthday) old

 Were clinically healthy

 Had a negative pregnancy test at the first medical examination, if female and capable of bearing children

 Agreed to employ adequate birth control measures for the duration of the study, if female and capable of bearing children

 Provided written informed consent

 For volunteers under 18 years of age - written informed consent of the parents / guardian was available

 Agreed to keep a volunteer diary

Exclusion criteria: :

 History of any previous TBE vaccination

 History of TBE infection or show evidence of latent TBE infection (as demonstrated by screening ELISA > 126 VIEU/ml)

 History of allergic reactions, in particular to one of the components of the vaccine

 Previously received volume substitution with a product containing polygeline (stabilizer in ENCEPUR)

 Received antipyretics within 4 hours prior to the first TBE vaccination

 Suffer from a disease that cannot be effectively treated or stabilized

 Suffering from a disease (e.g. autoimmune disease) or were undergoing any form of treatment that could be expected to influence immunological functions

 Suffering from chronic, degenerative and/or inflammatory disease of the central nervous system

 Using any immunosuppressive drugs (e.g. local or systemic corticosteroids, chemotherapeutics)

 Had a known or suspected problem with drug or alcohol abuse (> 4 liters wine / week or equivalent level of other alcoholic beverages)

 Had donated blood or plasma within one month of the study start

 Had received banked blood or immunoglobulins within one month of study entry

 Known to be HIV positive (a special HIV test was not required for the purpose of the study)

 Suffering from a febrile illness at study entry

 History of vaccination against yellow fever and / or Japanese B encephalitis

 Participating simultaneously in another clinical trial

 If female: pregnant or breast feeding

['Tick-Borne Encephalitis (TBE) Vaccine (Inactivated)']


Plain Magnetic Resonance (MR) in the Assessment of Patients With Acute Abdomen

Summary: At present, CT is the gold standard in the assessment of patients with acute abdomen. Yet, one CT of the abdomen exposes patients to a radiation dose equivalent to several years of background radiation. MR can be expected to yield the same information without ionizing radiation, but tends to be more time consuming. In this study, patients with nontraumatic acute abdominal pain referred to CT of the abdomen by the department of surgery will also have performed an additional MR scan covering the entire abdomen with few fast imaging sequences in approximately 15min. CT is the diagnostic test. The MR scan is only used for scientific purposes. It will be evaluated by a radiologist blinded for the results of the CT scan. Fourteen days after admission, a final diagnosis is established based on clinical, peroperative, pathological and lab. findings. The performance of CT and MR will then be compared. The investigators hypothesize that MR can provide a diagnostic accuracy comparable to CT.
Inclusion criteria: inclusion criteria:

 Signed informed consent form

 Age > 18 years old

 Nontraumatic acute abdomen

 Weight < 120kg

 Can keep apnoea for 15s

 Surgeon in charge considers patient fit for participation in study

Exclusion criteria: :

 Contraindications of MRI

 Suspicion of acute vascular disease

 Severe cardial or pulmonal insufficiency

 Pregnancy

 Untreated psychiatric illness


Childhood Schistosomiasis: a Novel Strategy Extending the Benefits/Reach of Antihelminthic Treatment

Summary: Objective and Hypotheses: This project has the overall objective of implementing and evaluating new approaches to reducing the current and future burden of urinary schistosomiasis in young children using the antihelminthic drug Praziquantel. The project aims to (1) determine the operational health benefits of treating schistosome infections early on re-infection and morbidity reduction, (2) determine if gut or urine microbiome structure (species diversity or abundance) is a risk factor for S. haematobium infection or morbidity, and (3) elucidate the factors and underlying mechanisms mediating the reduction/reversal of schistosome-related morbidity and resistance against infection/re-infection in young children.
Inclusion criteria: inclusion criteria:

 lifelong residents of the area

 have provided at least 2 urine and 2 stool for parasitological examination

 have given a blood sample before and after each treatment episode

 be negative for schistosomes, hookworm, Trichuris and Ascaris

 have frequent contact with infective water

Exclusion criteria: :

 clinical signs of tuberculosis or malaria

 presenting with fever

 have had a recent major operation, illness or vaccination

 have previously received antihelminthic treatment

 are infected with any helminths


Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

Summary: 96 TB subjects and 96 non-TB subjects with lung disease who all meet the standard are divided into different groups through a randomized, blind methods.Every subject inject intradermally ESAT6-CFP10 and TB-PPD in different arms of the same person.Specific γ- IFN(gamma interferon) detection is needed before the injection.Evaluate the sensitivity (positive coincidence rate) ,the specificity (negative coincidence rate) and the coincidence rate of ESAT6-CFP10 in the tuberculosis patients and non-tuberculosis patients with lung diseases, and determine the optimal dose of ESAT6-CFP10 for clinical auxiliary diagnosis of tuberculosis.
Inclusion criteria: inclusion criteria of TB (tuberculosis ) subjects:

 Diagnosis TB ;

 18 to 65 years ;

 Consent and signed informed consent forms(ICF) ;

 Comply with follow-up .

Exclusion criteria:  of TB (tuberculosis ) subjects:

 advanced cancer, diabetes,copd in acute episodes, acute/ progressive liver disease or kidney disease, congestive heart failure, etc ;

 Taking part in other clinical or within 3 months involved in any other clinical;

 histories of allergy ;

 in pregnancy or lactation;

 In a mental illness ;

 Any conditions affect the trial evaluation.

 inclusion criteria of Non-tuberculosis subjects with lung disease :

 Diagnosis non-tuberculosis subjects with lung disease ;

 18 to 65 years ;

 Consent and signed signed informed consent forms(ICF) ;

 Comply with follow-up .

['5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm', '5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm', '10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm', '10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm']


Efficacy Of Itraconazole In Chronic Cavitary Pulmonary Aspergillosis

Summary: The purpose of this study is to determine whether there itraconazole is effective in the treatment of chronic cavitary pulmonary aspergillosis
Inclusion criteria: inclusion criteria:

 Clinical symptoms: -presence of chronic pulmonary/systemic symptoms lasting ≥ six weeks.

 Radiological findings:

 Evidence of slowly progressive pulmonary lesions over weeks-months including cavities with surrounding inflammation.

 presence of intracavitary mass with a surrounding crescent of air,and presence of pleural thickening in peripheral lesions.

 Microbiological/Immunological findings: Positive results in the aspergillus precipitin test, demonstration of aspergillus hyphae in sputum or BAL fluid or cultures of BAL/sputum growing aspergillus species.

 The diagnosis of CCPA will be made if

 Patient satisfies at least 1, 2a or 2b and/ or any of the 3rd criteria.

 FNAC from the cavity wall will be considered in atypical cases

Exclusion criteria: :

 Invasive aspergillosis

 Allergic broncho-pulmonary aspergillosis (ABPA)

 Active tuberculosis or malignancy

 Pregnant females

['Itraconazole', 'treatment in cavitary pulmonary aspergillosis']

['Chronic Cavitary Pulmonary Aspergillosis']


Study to Evaluate the Diagnostic Value of a Combined Molecular Breast Imaging/ Breast Tomosynthesis Modality

Summary: The purpose of this pilot study is to investigate the potential clinical benefits of combining two new diagnostic tools to provide co-registered anatomical and functional information in the breast in patients with suspected breast cancer.
Inclusion criteria: inclusion criteria:

 over the age of 25

 enrolled in one of the following protocols:

 IRB # 08-005522: Evaluation of Molecular Breast Imaging in Patients with a High Likelihood of Ductal Carcinoma in Situ. 07-004241: Molecular Breast Imaging in the Preoperative Evaluation of Women with Biopsy Proven Breast Cancer. 1204-03: Evaluation of a Small Field of View Gamma Camera for Scintimammography in Patients with Atypical Ductal Hyperplasia, Atypical Lobular Hyperplasia, and Lobular Carcinoma In Situ. 07-003397: Comparison of MRI and Molecular Breast Imaging in Breast Diagnostic Evaluation. 17-05: Determination of the Sensitivity of a Dual-Headed Small Field of View Gamma Camera for the Detection of Small Breast Lesions.

 Digital mammogram at the Mayo Clinic within the past 30 days

Exclusion criteria: :

 They are unable to understand and sign the consent form

 They are pregnant or lactating

 They are physically unable to sit upright and still for 40 minutes.

 Recently enrolled on one of the ongoing tomosynthesis vs. mammography studies (rationale - avoid performing duplicate tomosynthesis studies in the same patient)