In-vivo Optical Coherence Tomography Imaging in Dermatooncology

Summary: In vivo differentiation of benign and malignant skin lesions is a fundamental issue in clinical dermatology. Malignant skin diseases are known to be accompanied by structural alterations. Conventional excisional biopsies and further histopathology are regarded as the reference standard for investigating these pathologies. Biopsies are invasive procedures and additionally may cause side effects. Therefore, research efforts are focused on the development of diagnostic techniques capable of providing in vivo information on the skin's structure. Optical coherence tomography (OCT) is a technical application, which allows the identification of microscopic patterns indicative for benign and malignant skin lesions. OCT is a promising noninvasive imaging technique for the micromorphology of the skin. So far, it's clinical application, as an additional diagnostic tool for malignant skin lesions has been studied in a limited extend. To evaluate the clinical usefulness of OCT, we conducted a prospective pilot study at the Department of Dermatology, Medical University of Vienna. The study is in cooperation with the Center of Biomedical Engineering and Physics at the Medical University of Vienna.~A total of 70 malignant skin lesions was evaluated during this prospective pilot study. Diagnoses based on OCT imaging as an additional diagnostic tool, were compared to those based on the clinical standard pathway at the Department of Dermatology, Medical University of Vienna. For the purpose of this study, the histopathological diagnosis was used as the reference diagnostic standard.~The major aims of this study is the investigation of the ability of ultrahigh resolution OCT to identify fine morphological characteristics associated with basal cell carcinoma, actinic keratosis, superficial squamous cell carcinoma, seborrheic keratosis, melanocytic nevi and melanoma.~To correlate the morphologic features identified with ultrahigh resolution OCT with routine histopathology~To investigate the clinical feasibility of ultrahigh resolution and spectroscopic OCT technology~To assess the effectiveness of ultrahigh resolution and spectroscopic OCT imaging to diagnose various melanocytic and non-melanocytic skin tumors~To compare the diagnostic capabilities of ultrahigh resolution OCT with standard non-invasive diagnostic procedures such as epiluminescence microscopy
Inclusion criteria: inclusion criteria:

 seborrhoeic warts

 nevi

 dermatofibroma

 basal cell carcinoma

 actinic keratosis

 squamous cell carcinoma

 Bowen's disease

 Merkel cell carcinoma

 malignant melanoma

Exclusion criteria: :

 employers of the Medical University of Vienna

 patients during compulsory military service

 patients with an appointed guardian

['in-vivo skin tumor imaging via optical coherence tomography']

['Non-melanocytic Skin Tumors', 'Melanocytic Skin Tumors']

Non-melanocytic Skin Tumors
Melanocytic Skin Tumors


ESWT as a Treatment for Chronic NHO in TBI Patients

Summary: Effect of Extracorporeal Shock Wave Therapy on Chronic Neurogenic Heterotopic Ossification in Traumatic Brain Injured (TBI) patients~Chronic Neurogenic Heterotopic Ossification (NHO) - Heterotopic ossification is a well known late complication of traumatic brain injury. Extracorporeal Shock Wave Therapy - ESWT- is used in various medical situations and is being tested for feasibility of use in TBI patients.
Inclusion criteria: inclusion criteria:

 Age > 18 years

 Brain injured patients with a diagnosis of NHO around the hip and/ or knee for a period of greater than one year.

 Patients who are able, or legal guardians who are willing, to provide informed consent after both oral and written information.

Exclusion criteria: :

 Pregnancy.

 Rheumatoid arthritis, ankylosing spondylitis, or femoral neck fractures

 Elevated serum alkaline phosphatase (SAP) levels and/or evidence of active bone remodelling in bone scan

['ESWT - Extracorporeal Shockwave Therapy']


Genetic Study of Familial Factors in Patients With Colon Cancer

Summary: RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer.~PURPOSE: Clinical trial to study the cancer-related genes in patients who have colon cancer or adenomatous polyps.
Inclusion criteria: DISEASE CHARACTERISTICS:

 Diagnosis of colon cancer or polyps at age 70 or under

 Has a living full sibling with diagnosis of colon cancer or polyps at age 70 or under

 No history of familial adenomatous polyposis syndrome

 No hereditary nonpolyposis colon cancer, according to Amsterdam criteria

 No known I1370K adenomatous polyposis of the colon susceptibility variant

 Enrolled on 1 of the following clinical trials:

 CLB-9581

 CLB-89803

 CLB-80001 NOTE: Patients do not need to be receiving protocol therapy. Patients who are outside the treatment protocol's follow-up range are eligible. Patients who discontinued therapy for any reason, including toxic effects, are eligible.

 PATIENT CHARACTERISTICS:

 Age

 70 and under at diagnosis

 Other

 No significant psychiatric illness that would preclude giving informed consent

 No inflammatory bowel disease (in patient or sibling)
Exclusion criteria:

['cytogenetic analysis', 'gene mapping', 'microarray analysis']

cytogenetic analysis
gene mapping
microarray analysis


Anterior Cruciate Ligament Pain Study

Summary: The objective of this study is to compare the pain control benefit of two different types of nerve blocks in patients undergoing anterior cruciate ligament (ACL) reconstruction.
Inclusion criteria: inclusion criteria:

 Patients undergoing scheduled anterior cruciate ligament (ACL) surgery at the Emory Orthopaedic and Spine Center

 Patients willing and able to provide written informed consent

 Parents willing and able to provide written informed consent for minors

Exclusion criteria: :

 Patients who are pregnant or lactating

 Patients with liver dysfunction or renal failure

 Patients with a known allergy to ropivacaine

 Patients with a local infection

 Patients who take chronic pain medications

 Patients with an opioid tolerance

 Patients with known coagulopathy or bleeding risk.

 Patients who are getting neuraxial anesthesia for surgery

['Ropivacaine 0.5%', 'Percocet 7.5/325', 'Naprosyn 500 mg']

Ropivacaine 0.5%
Percocet 7.5/325
Naprosyn 500 mg

['Anterior Cruciate Ligament Reconstruction']


Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST)

Summary: Trauma is the leading cause of death in people 44 years of age or younger. After major trauma, such as following high-speed motor vehicle collision, bleeding coupled with clotting defects is responsible for most of deaths in the first hours of hospital admission. Of note, these bleeding-related deaths are potentially preventable. Accordingly, the initial in-hospital management of severely injured patients focuses on stopping bleeding, replacing blood loss and correcting clotting defects.~Recently, animal and human research demonstrated that one of the major clotting defects following injury and bleeding is the drop in blood levels of fibrinogen (a clotting factor), which is detected on hospital admission in severely injured patients. These low fibrinogen levels are associated with increased blood transfusion and death. However, in North America, the standard of care for replacing low fibrinogen requires the use of cryoprecipitate, which is a frozen blood product with long preparation time, and similarly to other blood products, carries the risk of viral transmission and transfusion complications. Alternately, many Europeans countries where cryoprecipitate has been withdrawn from the market due to safety concerns, use fibrinogen concentrate. Fibrinogen concentrate undergoes pathogen inactivation, which is a process to eliminate the risk of transmitting viruses, bacteria and parasites, is likely a safer and faster alternative to cryoprecipitate. In Canada, fibrinogen concentrate is licensed for congenital low fibrinogen only.~Although preliminary data suggest that fibrinogen supplementation in trauma is associated with reduced bleeding, blood transfusion, and death, the feasibility, safety and efficacy of early fibrinogen replacement remains unknown. We proposed to conduct a feasibility randomized trial to evaluate the use of early fibrinogen concentrate against placebo in injured patients at our trauma centre.~A pilot trial is necessary to demonstrate the feasibility of rapidly preparing, delivering, and infusing fibrinogen concentrate as an early therapy to prevent excessive bleeding in trauma. This feasibility trial will provide preliminary safety and clinical outcome data to inform the design of larger trials; which ultimately aims to prevent bleeding-related deaths in the trauma population.
Inclusion criteria: inclusion criteria:

 1. Injured trauma (penetrating or blunt) patients who are at risk of significant bleeding, defined as: i. Systolic blood pressure (SBP) ≤ 100mmHg at any time from the injury scene until 30min after hospital admission AND ii. Red blood cell transfusion has been ordered by the trauma team leader (or delegate)

Exclusion criteria: :

 Patients in shock which the etiology is purely not related to bleeding:

 i. Cardiogenic (myocardial or valvular dysfunction); ii. Distributive (septic, anaphylactic, acute adrenal insufficiency and neurogenic) and iii. Obstructive (cardiac tamponade, tension pneumothorax and massive pulmonary emboli).

 Severe head injury, defined as any of the following:

 i. Glasgow coma scale (GCS) of 3 due to severe traumatic brain injury (TBI); ii. TBI with clear indication of immediate neurosurgical intervention based on clinical findings (mechanism of trauma associated with focal signs such as anisocoria with fixed pupil) or on CT results (bleeding causing mass effect); iii. Unsalvageable head injury such as through-through gunshot wound to the head, open skull fracture with exposure/loss of brain tissue; as per the trauma team or neurosurgery initial clinical assessment or as per initial CT of the head findings;

 Known complete or incomplete spinal cord injury;

 Known hereditary or acquired coagulopathies unrelated to the trauma resuscitation (e.g. known hepatic dysfunction);

 Use of anticoagulant medications such as warfarin, low-molecular weight heparin, and direct thrombin and factor Xa inhibitors;

 Moribund with evidence of unsalvageable injuries and withdrawal of care, as per the trauma team;

 Received blood products prior to admission;

 Patients with estimated body weight under 50Kg;

 Patients with known or suspected pregnancy;

 Patients arriving more than 6hr after injury.

['Fibrinogen concentrate', 'Placebo Comparator']

Fibrinogen concentrate
Placebo Comparator

['Trauma', 'Injury', 'Bleeding', 'Haemorrhage', 'Coagulopathy']

Trauma Injury Bleeding Haemorrhage Coagulopathy


Efficacy and Safety of Quetiapine Versus Quetiapine Plus Lithium in Bipolar Depression

Summary: The purpose of this study is to compare the efficacy of quetiapine fumarate monotherapy with quetiapine fumarate in combination with lithium in the treatment of a major depressive episode in patients with bipolar disorder.
Inclusion criteria: inclusion criteria:

 Outpatients that meet the diagnostic criteria for bipolar disorder I and bipolar disorder II with the most recent episode depressed

 The total score of the scale that's used for the evaluation of depression (HAM-D) should be ≥20

 The total score of the scale that' used for the evaluation of mania (YMRS) should be ≤12

Exclusion criteria: :

 Patients with a current DSM-IV-TR Axis I disorder other than bipolar disorder within 6 months of enrollment. Patients who pose a current serious suicidal or homicidal risk

 Use of drugs that induce or inhibit the hepatic metabolizing enzymes within 14 days before randomisation

 Patients who are unable to discontinue all psychoactive medications, including antidepressants, antipsychotics, and mood stabilizers at least 7 days prior to randomisation and consistent with the pharmacokinetics of the drug

['Quetiapine fumarate XR', 'Lithium carbonate']

Quetiapine fumarate XR
Lithium carbonate


Naproxen for the Prevention of HO After Complex Elbow Trauma

Summary: Complex elbow fractures can lead to formation of new bone (called Heterotopic ossification). This new bone is unwanted and it can restrict motion. This research study is being done to learn more about the effect of the drug naproxen, on unwanted formation of new bone around the elbow as it heals after a fracture. Naproxen belongs to a class of drugs called NSAIDs which stands for non-steroidal anti-inflammatory drugs.~Several research studies suggest that NSAIDs such as Naproxen can prevent the unwanted formation of new bone around the hip. The effect of NSAIDS on the formation of bone around the elbow has not been studied as well as it has been studied for their effect on the hip.~The drug, Naproxen is approved by the US food and drug administration (FDA) for sale but ot specifically for the treatment of heterotopic ossification.
Inclusion criteria: inclusion criteria:

 Subjects aged 18 years or greater

 Operative treatment of one of the following injuries

 An elbow dislocation with or without associated fractures

 An olecranon fracture-dislocation, but not simple olecranon fractures

 A distal humerus fracture

Exclusion criteria: :

 An existing diagnosis of one of the following conditions

 Injury to the central nervous system, thorax, or abdomen precluding the immediate use of non-steroidal anti-inflammatory medications

 Fracture of any long bone since non-steroidal anti-inflammatory medications may increase the risk of nonunion

 History of gastritis, peptic ulcer disease, or upper gastrointestinal bleeding

 Impaired renal function (creatinine > 2.0), hypovolemia, heart failure, high blood pressure ( > 160/90), fluid retention, asthma, liver dysfunction (bilirubin > 2.0), or a coagulation disorder

 Allergy to non-steroidal anti-inflammatory medications

 Asthma, nasal polyps, urticaria, and hypotension associated with the use of NSAIDs

 Considerable dehydration

 Pregnant or breast-feeding women

 Concomitant use of one of the following drugs:

 Aspirin

 Other naproxen products (ec-naprosyn, anaprox, anaprox ds, naprosyn suspension, aleve)

 Methotrexate

 Diuretics (thiazides / furosemide)

 ACE-inhibitors (captopril, enalapril, ramipril etc.)

 Beta-blockers (propanolol etc.)

 Probenecid (for gout or hyperuricemia)

 H2-blockers, sucralfate and intensive antacid therapy

 Lithium

 Anticoagulants / Warfarin (coumadin, waran, jantoven etc.)

 Sulfonamides

 Anticonvulsant medication (peganone, mesantoin, cerebyx, dilantin, etc.)


Genetic and Neural Predictors of Adolescent Depression

Summary: This study aims to examine the relationship between mood and brain activity in adolescent girls in order to better understand the genetic and neural predictors of adolescent depression. The participants in this study will be healthy female adolescents aged 12-14 and their mothers. They will participate for a total of six months. Adolescent participants will have three study sessions at McLean Hospital, and during two of them, their mothers will also have assessments. Adolescent assessments will include interviews, questionnaires, computer tasks, and collection of a saliva sample for genetic analyses. Their second study visit will include an fMRI scan. Parent assessments will include an interview, questionnaires, and a computer task.
Inclusion criteria: Adult Cohort

 A. MDD Mothers Cohort inclusion criteria:

 Current or past Major Depressive Disorder

 English as first language or English fluency

 Biological daughter who meets inclusion/
Exclusion criteria:  for High Risk Female Adolescent

 B. Healthy Control Mothers Cohort inclusion criteria:

 No history of psychopathology

 English as first language or English fluency

 Biological daughter who meets inclusion/


Towards Better Prognostic and Diagnostic Strategies for Haemostatic Changes During Major Obstetric Haemorrhage

Summary: Major obstetric haemorrhage (MOH) remains a cause of significant maternal morbidity and mortality worldwide. By identifying women with a higher a priori risk of major haemorrhage during their pregnancy or early during postpartum haemorrhage extra measures to prevent MOH can be taken.~In this study the investigators aim to identify haemostatic parameters that during the course of haemorrhage are responsible for the on-going towards major bleeding. By doing this, cut-off points can be defined for future interventions aiming to stop this bleeding process in an early stage. Traditional coagulation parameters are currently not useful for clinical decision making, because of long turn around times. Therefore the added value of available coagulation 'point of care' tests will be evaluated during obstetric haemorrhage.These Point-of-Care (POC) tests could lead to a goal-directed haemostatic therapy for obstetric haemorrhage.~A cohort of 9.500 pregnant women will be followed during their pregnancy and delivery. From all women a bleeding score will be obtained during their pregnancy by means of a validated questionnaire. The predictive value of this bleeding score for the occurrence of major obstetric haemorrhage will be evaluated.~If postpartum haemorrhage develops (blood loss) > 1000 cc, blood samples will be drawn for conventional haemostatic parameters and ROTEM profiles. The pathway between minor bleeding and major bleeding will be elucidated. Interchangeability and comparability of conventional haemostatic parameters and ROTEM profiles will also be evaluated.~The overall goal of the investigators is becoming more able to predict major obstetric haemorrhage in an early stage of postpartum haemorrhage and define thresholds for goal-directed hemostatic therapies.
Inclusion criteria: inclusion criteria:

 - Pregnancy, gestation age > 24 weeks

Exclusion criteria: :

 Age < 18

 Adults incapable of giving informed consent

 Gestational age < 24 weeks


Role of Prostaglandins in the Regulation of Brain Blood Flow

Summary: This study will use magnetic resonance imaging (MRI) to examine the role of prostaglandins-a type of fatty acid with hormone-like actions-in the regulation of brain blood flow. The results will provide information on how to better use this technique to study brain function, which, in turn, may lead to a better understanding of certain illnesses and more effective treatments.~Healthy normal volunteers 18 years of age and older may be eligible for this study. Participants will fill out a health questionnaire and undergo a history, physical examination and MRI studies. MRI is a diagnostic tool that uses a strong magnetic field and radio waves instead of X-rays to show structural and chemical changes in tissues. During the scanning, the subject lies on a table in a narrow cylinder containing a magnetic field. An intercom system allows the subject to speak with the staff member performing the study at all times during the procedure. Four separate studies will be done-two carbon dioxide inhalation studies and two functional activation studies-as follows:~Carbon dioxide inhalation (indomethacin): This study is done in two parts. In both parts, an MRI brain scan is done. During the scan, the subject inhales an air mixture containing 6% carbon dioxide through a facemask or mouthpiece. Blood pressure and heart rate are monitored during inhalation of the mixture. For the second part of the study, indomethacin-a non-steroidal anti-inflammatory drug-is injected through a catheter (thin flexible tube) in an arm vein. Indomethacin inhibits prostaglandin production. Total scan time averages between 45 and 90 minutes, with a maximum of 2 hours.~Carbon dioxide inhalation (rofecoxib and celecoxib): This study is identical to the one above, except either rofecoxib or celecoxib is given instead of indomethacin. Both of these drugs are also non-steroidal anti-inflammatory drugs that inhibit prostaglandin production. Unlike indomethacin, rofecoxib and celecoxib are given orally instead of through a vein, so, to allow time for the drug to be absorbed, the second scan is delayed for 2 hours.~Functional activation (indomethacin): This study is done in two parts. In both parts, a MRI brain scan is done. During the study, the subject performs a simple motor task, such as finger tapping. For the second part of the study, indomethacin is injected through a catheter in an arm vein.~Functional activation (rofecoxib and celecoxib): This study is identical to the indomethacin functional activation study, except either rofecoxib or celecoxib is given instead of indomethacin. Because they are given orally instead of through a vein, the second scan is delayed 2 hours to allow time for the drug to be absorbed.
Inclusion criteria: inclusion criteria:

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

Exclusion criteria: :

 Subjects will be excluded for the following reasons.

 They have contraindications to MR scanning, such as the following: aneurysm clip, implanted neural stimulator, implanted cardiac pacemaker or autodefibrillator, cochlear implant, ocular foreign body (e.g., metal shavings), or insulin pump.

 They have panic disorder or migraine (because of possible complications with CO2 inhalation).

 They have cirrhosis, any renal dysfunction, or a chronic respiratory illness (such as asthma).

 They have allergies to sulfonamide drugs or cyclo-oxygenase inhibitors (NSAIDS).


Detecting Chronic Subdural Hematoma With Microwave Technology

Summary: An open study evaluating the sensitivity and specificity of a microwave-based device, Medfield Strokefinder MD100, to detect chronic subdural hematoma, by comparing measurements on patients recruited for surgery of chronic subdural hematoma to an age- and gender-matched group of healthy volunteers.
Inclusion criteria: inclusion criteria:

 Patient admitted for surgery of chronic subdural hematoma.

 A CT scan of the patient has been performed, within the latest 96 hours.

 The patient should be able to have a normal conversation and understand the information about the study, corresponding to Glasgow Coma Scale (Verbal Response) of 5.

 Patient/healthy volunteer should be ≥ 18 years of age.

 The patient/healthy volunteer has signed a written informed consent.

Exclusion criteria: :

 Females who are pregnant or breast feeding women.

 Patient/healthy volunteer has a shunt or other foreign object implanted in the brain.

 Patient/healthy volunteer participating in any other clinical study that could interfere with the result in the ongoing study.

['Chronic Subdural Hematoma', 'Healthy Volunteers']

Chronic Subdural Hematoma
Healthy Volunteers


Improving Diabetic Foot Ulcers With Atorvastatin

Summary: Lower limb complications are a substantial matter in the diabetic population and studies show that the annual incidence of foot ulcers ranges from 1.0-4.1% while the cumulative lifetime incidence is approximately 15%. Foot ulcers may become complicated by infection or gangrene, and ultimately result in amputation. In addition, foot ulcers have a significant impact on quality of life (QoL). The treatment of diabetic foot ulcers has not made substantial progress in recent years with regards to improved healing although there have been several actions taken to update the process. The current practice consists of wound debridement, treatment of underlying infections and pressure relief. This trial investigates the adjunctive effects of high (80 mg) or low (10 mg) dose atorvastatin to conventional treatment on the healing of diabetic foot ulcers.
Inclusion criteria: inclusion criteria:

 Provision of a written informed consent at the enrolment visit

 Men or women above 30 years of age

 Fertile women need to take contraceptives or have to be sterilised

 Diagnosed with any diabetes mellitus type 1 or type 2

 Present foot ulcer with an ulcer duration <= 12 months

Exclusion criteria: :

 Intolerance to statins at any time in the past.

 Unwillingness to participate

 A history of alcohol or drug abuse within the last 2 years

 Foot ulcer with the etiology from vasculitis, pyoderma gangrenosum, angiodermatitis necroticans (hypertensive ulcer), necrobiosis lipoidica, hydrostatic pressure/venous insufficiency or any neoplasms (basalioma, kaposis sarcoma, squamous cell carcinoma etc).

 History of drug-induced hepatitis or previous liver enzyme elevations (> 3 times the upper limit of normal) while taking statins.

 History of drug-induced creatine phosphokinase (CPK) > 3 times the upper limit of normal.

 Critical limb ischemia that requires re-vascularisation procedures within 2 months

 Brachial-ankle index < 0.5

 Other serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the patient's safety or successful participation in the trial.

 Any clinically significant abnormality identified in the enrolment medical history, physical examination, laboratory test which, in the judgement of the investigator, would preclude safe completion of the study.

 Active liver disease or hepatic dysfunction defined as ALAT or ASAT elevations > 2 times the upper limit of normal or total bilirubin > 1.5 times the upper limit of normal.

 Pregnancy


Echo-Cardiographic Assessment of Cardiovascular Characteristics During Pregnancy and Postpartum Periods

Summary: The purpose of this echocardiographic study is to restudy the longitudinal changes in cardiac size and function during and after pregnancy in healthy women using relatively new parameters of systolic and diastolic function as well as classical measures of left ventricle (LV) function using contemporary echocardiographic machines.~We, the researchers at Hillel Yaffe Medical Center, will assess diastolic function and its possible relation to shortness of breath.
Inclusion criteria: inclusion criteria:

 Healthy women

 First trimester of a normal pregnancy

 Normal baseline echocardiogram

Exclusion criteria: :

 Pregnancy with more than one fetus.

 Any hemodynamically significant cardiac condition

 Any known systemic disease

 Poor quality echocardiogram


Cerebrospinal Fluid (CSF) Drainage and Cytokine Profiling in the Treatment of Acute Spinal Cord Injury (SCI)

Summary: The overall purpose of this pilot study is to evaluate CSF drainage as a potential neuroprotective strategy after acute spinal cord injury (SCI).
Inclusion criteria: inclusion criteria:

 Injured subjects:

 Complete or incomplete acute SCI between C0 and T11

 Admitted within 48 hours of injury

 Undergoing spinal decompressive surgery

 Undergoing lumbar puncture for spinal anesthetic or myelography

 Neurologically intact

Exclusion criteria: :

 Pre-existing neurodegenerative disorder

 Associated head or spine injury


Dose-finding Study to Investigate the Safety and Immunogenicity of Two Vaccinations With FSME IMMUN NEW in Healthy Volunteers Aged 1 to 6 Years.

Summary: The purpose of this study is to investigate the safety and immunogenicity of three different concentrations of a TBE vaccine in healthy children aged 1 to 6 years.
Inclusion criteria: inclusion criteria:

 Male and female children will be eligible for participation in this study if:

 they are 1 year (from the 1st birthday) to 6 years (to the last day before the 6th birthday) old;

 they are clinically healthy;

 their legal representative understands the nature of the study, agrees to its provisions and gives written informed consent;

 their legal representative agrees to keep a Volunteer Diary.

Exclusion criteria: :

 Children will be excluded from participation in this study if they:

 have a history of any previous TBE vaccination;

 have a history of TBE infection or show evidence of a latent TBE infection (as demonstrated by screening ELISA > 126 VIEU/ml and / or neutralization test > 1:10);

 have a history of allergic reactions, in particular to one of the components of the vaccine;

 have received antipyretics within 4 hours prior to the first TBE vaccination;

 suffer from a disease that cannot be effectively treated or stabilized;

 suffer from a disease (e.g. autoimmune disease) or are undergoing a form of treatment that can be expected to influence immunological functions;

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

 are known to be HIV positive (a special HIV test is not required for the purpose of the study);

 suffer from a febrile illness at study entry;

 have a history of vaccination against yellow fever and / or Japanese B-encephalitis;

 are participating simultaneously in another clinical trial.


Foscarnet Treatment of Serious CMV Retinitis Infection in Patients With Acquired Immunodeficiency Syndrome

Summary: To explore the safety and usefulness of foscarnet, an antiviral agent, in the treatment of cytomegalovirus (CMV) retinitis. Untreated CMV retinitis is a rapidly progressive, blinding disease in AIDS patients. The manner in which foscarnet breaks down in the body and the effect of increasing periodic intravenous doses are also studied. Foscarnet is active in vitro (test tube) against herpes viruses, including CMV, by inhibiting the virus DNA polymerases, enzymes necessary for virus replication, without affecting cellular DNA polymerases. Opportunistic CMV disease in AIDS is usually seen as retinitis, colitis, esophagitis, hepatitis, pancreatitis, encephalitis, or pneumonia. Ganciclovir has been used to treat AIDS patients with CMV disease but can cause severe neutropenia (very low neutrophil cell counts). Foscarnet does not suppress the production of neutrophils or other leukocytes (myelosuppression) and has shown in vitro activity against HIV.
Inclusion criteria:
Exclusion criteria:

 Concurrent Medication:

 Excluded:

 Acyclovir.

 Zidovudine (AZT).

 Any potentially nephrotoxic agent, especially aminoglycosides, pentamidine, or amphotericin B.

 Prior Medication:

 Excluded:

 Ganciclovir.

 Foscarnet.

 Excluded within 7 days of study entry:

 Any potentially nephrotoxic agent.

 Excluded within 14 days of study entry:

 Cytomegalovirus hyperimmune globulin in therapeutic doses.

 Immunomodulators.

 Biologic response modifiers.

 Investigational agents.

 Amphotericin B maintenance for a systemic mycosis.

 Known allergy to foscarnet.

 Active AIDS-defining opportunistic infection other than cytomegalovirus (CMV) including systemic mycosis, pulmonary or neurologic impairment (comatose).

 Patient must be diagnosed as having:

 AIDS CDC Group IV.C.

 Cytomegalovirus (CMV) retinitis as identified by its characteristic ophthalmoscopic appearance and verified by fundus photography.

 One pending culture for CMV from blood and urine prior to study entry.

['Cytomegalovirus Retinitis', 'HIV Infections']

Cytomegalovirus Retinitis
HIV Infections


Tissue Biopsy and Imaging Studies in HIV-Infected Patients

Summary: This study will examine tissue from the tonsils, lymph nodes and large bowel of HIV-infected patients to investigate changes in viral load and certain white blood cells during treatment.~Normal volunteers and HIV-infected patients 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests and possibly an electrocardiogram (EKG). Blood tests may include HLA typing, a genetic test of immune system markers.~Participants may undergo the following procedures:~Blood tests (patients and volunteers)~Biopsies The frequency of biopsies for given patients may vary, depending on their specific therapy. Typically, biopsies are done at a single time, or for patients starting a new therapy, biopsies could be performed before starting therapy, during therapy and possibly after completion of therapy.~Tonsil biopsies (patients and volunteers) Volunteers will have one tonsil biopsy. Patients will have no more than six tonsil biopsies, with no more than three in a 10-day period. The biopsy is done by an ear, nose and throat specialist as an outpatient procedure. The tonsils are numbed with a local anesthetic, and one to four pieces of tissue are extracted.~Lymph node biopsies (patients only) Patients will have no more than four lymph node biopsies, performed no more frequently than once a month. The biopsy is done by a surgeon and may require a 2- to 3-day hospital stay. The skin above the lymph nodes is numbed with a local anesthetic, an incision is made and the tissue is removed. Alternatively, a needle biopsy may be done, in which a small amount of lymph tissue is withdrawn through a special needle injected into the site.~Intestinal biopsies (patients and volunteers) Volunteers will have one intestinal biopsy procedure. Patients may have up to six intestinal biopsy procedures, each separated by at least 10 days. This is done by a gastroenterologist as an outpatient procedure. A flexible tube (sigmoidoscope or colonoscope) with a light and special lens at the tip is inserted into the rectum and large bowel. Wire instruments passed through the tube are used to extract small tissue samples.~Bronchoalveolar lavage (BAL; patients and volunteers) Volunteers and patients will undergo bronchoscopy in which a flexible tube (bronchoscope) with a light and special lens at the tip is inserted through the nose or mouth into the lungs, and the lining of the lung is sampled by washing the airways with small amounts of saline. The procedure is performed by a pulmonologist or critical care specialist, usually as an outpatient.
Inclusion criteria: inclusion criteria:

 Greater than or equal to 18 years old.

 Ability to sign informed consent.

 For women of child-bearing potential, negative result on a serum or urine pregnancy test within 1 week prior to the procedure.

 Willingness to allow storage of blood or biopsy samples for possible future use to study HIV/AIDS, related diseases or the immune system; willingness to permit HLA testing.

 FOR PATIENTS UNDERGOING BIOPSIES:

 No medical contraindication to tonsillar, lymph node, or intestinal biopsy.

 For tonsillar biopsy, presence of visible tonsillar tissue; for lymph node biopsy, palpable lymph nodes.

 No aspirin or piroxicam (Feldene) for 10 days prior to the procedure; other non steroidal anti-inflammatory drugs (e.g. ibuprofen) must be discontinued the day prior to the procedure. Acetaminophen [Tylenol] is permitted at any time.

 FOR PATIENTS UNDERGOING BAL:

 Hematocrit greater than 27 percent, platelets greater than 50,000/ml.

 Baseline pulse-oximetry recording of 94 percent or greater unless clinical indication for bronchoscopy.

 No medical contraindication to bronchoscopy.

 In addition to the above:

 FOR HIV POSITIVE VOLUNTEERS:

 HIV infection must be confirmed by ELISA and western blot or dot blot. For patients with acute HIV infection and negative HIV serology, plasma HIV viral load greater than 10,000 copies/ml.

 FOR HEALTHY VOLUNTEERS:

 No underlying significant medical problem, especially an immunodeficiency or autoimmune disease, or an underlying problem requiring immunosuppressive therapy.

 Absence of HIV infection as confirmed by negative ELISA and, if indicated, western blot or dot blot.

 FOR ICL PATIENTS:

 Patients must meet the definition of ICL according to the CDC criteria: documented absolute CD4 T lymphocyte count of less than 300 cells per cubic millimeter or of less than 20 percent of total T cells on more than one occasion usually two to three months apart, without evidence of HIV infection or any defined immunodeficiency or therapy associated with depressed levels of CD4 T cells.

 Absence of HIV infection as confirmed by negative ELISA and, if indicated, western blot or dot blot.

Exclusion criteria: :

 FOR ALL VOLUNTEERS UNDERGOING BIOPSIES:

 Platelet count less than 75,000 platelets/mm(3).

 PT or PTT prolonged by greater than 2 seconds unless patient has documented lupus anticoagulant/anti-phospholipid syndrome, which is not associated with an increased bleeding risk

 Known underlying bleeding disorder.

 Pregnancy.

 FOR HIV-POSITIVE OR ICL VOLUNTEERS FOR LYMPH NODE BIOPSIES:

 Use of narcotics (other than as prescribed by a physician) or cocaine less than 1 week prior to the date of biopsy.

 FOR ALL VOLUNTEERS FOR INTESTINAL BIOPSIES:

 Use of narcotics (other than as prescribed by a physician) or cocaine less than 1 week prior to the date of biopsy.

 Significant heart valve abnormalities.

 Presence of pacemaker, artificial joint or vascular surgery graft.

 FOR ALL VOLUNTEERS FOR BAL:

 Use of narcotics (other than as prescribed by a physician) or cocaine less than 1 week prior to the date of biopsy.

 Pregnancy.

 Any medical condition for which the investigators believe bronchoscopy may be contraindicated.

 Allergy to lidocaine.

 History of asthma requiring therapy.


Safety Study of Outpatient Treatment for Pulmonary Embolism

Summary: The purpose of this randomized clinical trial is to determine whether outpatient treatment is as effective and safe as inpatient treatment among low-risk patients with pulmonary embolism.
Inclusion criteria: inclusion criteria:

 age >18 years

 objectively confirmed diagnosis of pulmonary embolism

 patients at low-risk (Pulmonary Embolism Severity Index score <=85)

Exclusion criteria: :

 patients at high-risk (Pulmonary Embolism Severity Index score >85)

 presence of hypoxemia (arterial SO2 <90% measured by pulse oximetry or an paO2 on room air of <60 mm Hg measured by blood gas analysis)

 systolic blood pressure of <100 mm Hg

 chest pain necessitating parenteral opioid administration

 active bleeding or at high-risk of major bleeding (stroke during the preceding 10 days, gastrointestinal bleeding during the preceding 14 days, or platelets <75,000 per mm3)

 renal failure (creatinine clearance of <30 ml/minute based on the Cockcroft-Gault formula)

 body mass >150 kg

 history of HIT or allergy to heparins

 therapeutic oral anticoagulation (INR ≥2)at the time of pulmonary embolism diagnosis

 potential barriers to treatment adherence or follow-up (alcoholism, illicit current or recent drug use, psychosis, dementia, homelessness, lack of telephone access, transportation time to nearest ED >45 minutes)

 known pregnancy

 imprisonment

 diagnosis of pulmonary embolism >23 hours ago

 refusal or inability to provide informed consent

 prior enrollment in the study

['Outpatient care (vs traditional inpatient care)']


Role of Stem Cells in Improving Implantation Rates in ICSI Patients

Summary: Background:~Improving implantation rates in ICSI cycles has been the focus of research in recent decades. Because success rates is not satisfactory enough especially when transferring good embryos to the uterine cavity and pregnancy does not occur. Trying to improve endometrial receptivity, the investigators have thought about stem cell therapy as stem cells have played a pivotal role in regenerative medicine in many pathologies as myocardial infarction, Diabetes Mellitus and spinal cord injuries.~Garget and Healy reported in 2011 treatment of a case with Asherman's syndrome by administration of bone marrow stem cells in the uterine cavity. Endometrial growth and improved vascularity has been observed by ultrasound follow-up and Doppler study of endometrial blood flow. Endometrial regeneration has been enough to support pregnancy through successful IVF trial.~The investigators have succeeded in previous work to isolate MSC from placental tissue and differentiate it to endometrium-like cells. The investigators compared the differentiation ability of placental derived mesenchymal stem cells (MSC) and Wharton Jelly derived MSC to differentiate to endometrium under 3 different culture conditions: endometrium conditioned medium (ECM), follicular fluid (FF) conditioned medium and medium containing both. The investigators found that placental MSC has better differentiating ability to endometrium especially under culture conditions containing both ECM and FF as evidenced by prominent appearance of glandular pattern and expression of progesterone receptors in differentiated cells.~Therefore the investigators need to direct this study and test the effect of placental derived MSC in improving implantation rates in patients with recurrent implantation failure, unresponsive endometrium to ovulation induction drugs or with endometrial atrophy or advanced maternal age planning for ICSI trial.~Patients and Methods:~60 patients attending Kasr El-Aini assisted reproduction unit and private IVF center will be randomized to three groups by computer generated programs:~The first group, patients randomized to receive differentiated stem cell therapy:~After ovum pick-up, MSC differentiated to endometrium is deposited in the uterine cavity through an IUI catheter. Embryo transfer will be done at day 5 at the blastocyst stage to allow enough time for endometrial regeneration and increased endometrial receptivity.~The second group, patients randomized to receive undifferentiated stem cell therapy:~Immediately postmenstrual undifferentiated MSC is deposited in the uterine cavity through an IUI catheter to allow enough time for the MSC to differentiate as it needs 7-10 days for differentiation. Ovum pick-up will be done as usual while all other steps will be the same including embryo transfer which will be done at day 5.~The third group, control group:~Patients are randomized to receive no stem cell therapy; All ICSI steps from ovulation induction protocol to embryo transfer conditions will be the same for all groups.~Informed consent will be taken from the patients after detailed explanation of all steps of the procedure.
Inclusion criteria: inclusion criteria:

 ICSI candidates with repeated implantation failure and history of development of good embryos in previous ICSI cycles.

 Advanced maternal age above 38 years.

 Poor endometrial response to ovulation induction drugs.

 Endometrial atrophy.

Exclusion criteria: :

 Presence of infection in the form of vaginitis, cervicitis or hydrosalpinx.

 Presence of uterine abnormality as uterine septum.

 Presence of any pathology distorting the uterine cavity as:

 submucus polyp or submucus myoma.

 Marked sperm morphology abnormality.

 High FSH > 12 IU.

['Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter', 'Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter.']

['Assess the Efficacy of Differentiated and Undifferentiated Stem Cell Therapy in Improving Endometrial Receptivity.']


Study Comparing Etanercept (ETN) Against a Placebo for Etanercept on a Background Nonsteroidal Anti Inflammatory Drug (NSAIDs) in the Treatment of Early Spondyloarthritis (SpA) Patients Who do Not Have X-ray Structural Changes

Summary: This is a two part study. During period one there will be a comparison of Etanercept (ETN) against a placebo with both arms maintaining the background anti inflammatory drug prescribed by their Physician. The hypothesis is that Etanercept will be superior to the placebo arm as determined by the proportion of subjects achieving Assessments in Ankylosing Spondylitis (ASAS)40 improvement at 12 weeks. This will be followed by 92 weeks extension where everyone in the trial receives Etanercept (ETN) and a background non steroidal anti inflammatory drug(NSAID).
Inclusion criteria: inclusion criteria:

 Diagnosis of axial spondyloarthritis as defined by Assessments in Ankylosing Spondylitis (ASAS)criteria

 Active symptoms defined as Ankylosing Spondylitis Disease Activity Index{BASDAI) > or = 4

 Axial symptoms of back pain with a less than favorable response to on steroidal anti inflammatory drugs at optimal dosage for greater than 4 weeks

Exclusion criteria: :

 Evidence of current or recent episode of uveitis

 Evidence of IBD flare within 6 months

 Previous treatment with an anti Tumor necrosis factor(TNF)

 Active tuberculosis

 Radiographic sacroiliitis grade 3-4 unilaterally or >= 2 bilaterally

['etanercept', 'Background NSAID', 'PLACEBO', 'Background NSAID']

etanercept
Background NSAID
PLACEBO
Background NSAID


The SNORES Randomized Clinical Trial

Summary: Randomized clinical trial among women with polycystic ovary syndrome (PCOS) who present for fertility treatment to evaluate the impact of screening for obstructive sleep apnea.
Inclusion criteria: inclusion criteria

 Females 18 - 50 years old.

 Receiving care from an Obstetrician / gynecologist or a Reproductive endocrinology infertility specialist

 Polycystic ovarian syndrome defined by the modified Rotterdam criteria

 Able to speak and understand as well as give informed consent in English

Exclusion criteria:

 Late onset congenital adrenal hyperplasia

 Cushings disease

 Androgen-secreting tumors

 Previous diagnosis of obstructive sleep apnea

 Current use of over the counter or prescribed sleep medications.

 Examples of medications that exclude a patient from this study include but are not limited to Unisom, Ambien or Lunesta.

 Patients who are taking non-prescribed herbal medications for sleep will not be excluded from the study. Examples of these include but are not limited to melatonin, chamomile, or valerian.

 Untreated thyroid disease

 Prolactin excess

 Patients with the following medical conditions will be excluded from the study as portable sleep apnea monitors are not indicated in patients with severe pulmonary disease, neuromuscular disease, or congestive heart failure.

['Screening for obstructive sleep apnea', 'CPAP - continuous positive airway pressure']


Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus

Summary: The trial is designed to investigate differences in outcome of patients with esophageal adenocarcinoma and junctional adenocarcinoma treated with perioperative (neoadjuvant + adjuvant) chemotherapy (FLOT) plus surgical resection versus neoadjuvant chemoradiation (CROSS) plus surgical resection.
Inclusion criteria: inclusion criteria:

 Histologically verified adenocarcinoma of the esophagus according to the UICC definition (TNM7)

 Pre-treatment stage cT1N+, M0 or cT2-4a, N0/+, M0

 Age ≥18 years

 No prior abdominal or thoracic radiotherapy

 ECOG Performance status 0-2

 Adequate cardiac function ( Patients with a cardiac history (e.g. myocardial infarction, heart failure, coronary artery disease) should have a cardiology review)

 Adequate bone marrow function (WBC>3x10^9/l; Hb>9g/dl; platelets >100x10^9/l)

 Adequate respiratory function. Symptomatic Patients should have pulmonary function tests with FEV1 >65% of predicted)

 Adequate renal function (GFR >60ml/min)

 Adequate liver function (serum bilirubin <1.5x Upper level of Normal (ULN); AST <2.5x ULN and ALT <3x ULN (ULN as per institutional standard)

 written informed consent

Exclusion criteria: :

 Tumors of squamous or other non-adenocarcinoma histology

 Patients with advanced inoperable or metastatic esophageal adenocarcinoma

 Stage cT1N0 and cT4b

 Gastric carcinoma

 Prior chemotherapy for cancer,

 Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months)

 Clinical significant lung disease (FEV1 <65% of predicted)

 Peripheral neuropathy Grade >1

['5-Fluorouracil', 'Leucovorin', 'Oxaliplatin', 'Docetaxel', 'Carboplatin', 'Paclitaxel', 'Neoadjuvant radiation']

5-Fluorouracil
Leucovorin
Oxaliplatin
Docetaxel
Carboplatin
Paclitaxel
Neoadjuvant radiation

['Esophageal Adenocarcinoma (UICC TNM7)', 'Adenocarcinoma of the Esophagogastric Junction']


REBEAT Resynchronisation and Beta-Blocker European Trial

Summary: This protocol will evaluate the effect of cardiac resynchronization therapy (CRT) combined with beta-blocker therapy in patients with symptomatic heart failure in whom beta-blocker therapy was either not tolerated or could not be up titrated to optimal doses before CRT. Cardiac resynchronization therapy will be combined with automatic implantable cardioverter defibrillator (AICD, CRT-D) as it has been shown to be associated with an improvement in prognosis in the patients with left ventricular systolic dysfunction and heart failure.
Inclusion criteria: inclusion criteria:

 Symptomatic heart failure and indication for cardiac resynchronization therapy (CRT), Hemodynamic stability with documented intolerance to beta-blocker therapy or treatment with beta-blocking agents at sub-optimal dosages (<25% of optimal dosage).

Exclusion criteria: :

 chronic atrial fibrillation; indications for permanent antibradycardia pacing; mechanical tricuspid valve; Severe aortic stenosis or other primary valve disease causing cardiomyopathy


Lamotrigine in the Treatment of Binge Eating Disorder Associated With Obesity

Summary: This research study is to evaluate the effectiveness, tolerability, and safety of lamotrigine therapy in the treatment of binge eating disorder associated with obesity.~Lamotrigine has been approved by the Food and Drug Administration for the treatment of bipolar disorder, but has not been approved for use in the treatment of binge eating disorder with obesity.
Inclusion criteria: inclusion criteria:

 Patients will meet DSM-IV-TR criteria for BED for at least the last 6 months, determined by the Structured Clinical Interview for DSM-IV-TR (SCID) (61) and supported by the Eating Disorder Examination (EDE) (62). These criteria are as follows:

 Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:

 eating, in discrete period of time (e.g., within any two hour period), an amount of food that is definitely larger than most people would eat in a similar period of time under similar circumstances

 a sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating)

 The binge eating episodes are associated with at least three of the following:

 eating much more rapidly than normal

 eating until uncomfortably full

 eating large amounts of food when not feeling physically hungry

 eating alone because of being embarrassed by how much one is eating

 feeling disgusted with oneself, depressed, or feeling very guilty after overeating

 Marked distress regarding binge eating.

 The binge eating occurs, on average, at least two days a week for six months.

 Does not occur exclusively during the course of bulimia nervosa and anorexia nervosa.

 Obesity, defined by body mass index > 30 kg/m2.

 Men or women, between the ages of 18 and 65.

Exclusion criteria: :

 Have current body mass index < 30 kg/m2.

 Women who are pregnant or lactating and women of childbearing potential who are not taking adequate contraceptive measures. (All women of childbearing potential will have a negative pregnancy test before entering the study.)

 Subjects who are displaying clinically significant suicidality or homicidality.

 Subjects who are displaying a current clinically unstable depressive or bipolar disorder, defined as a Montgomery Asberg Depression Rating Scale (MADRS) (63) > 24 or a Young Mania Rating Scale (YMRS) (64) > 8.

 A current or recent (within 6 months of the start of study medication) DSM-IV-TR diagnosis of substance abuse or dependence.

 A lifetime history of a DSM-IV-TR psychotic disorder or dementia.

 History of a personality disorder (e.g., schizotypal, borderline, or antisocial) which might interfere with assessment or compliance with study procedures.

 Clinically unstable medical disease, including cardiovascular, hepatic, renal, gastrointestinal, pulmonary, metabolic, endocrine or other systemic disease which could interfere with diagnosis, assessment, or treatment of binge eating disorder. Patients should be biochemically euthyroid prior to entering the study.

 History of seizures, including febrile seizures in childhood.

 Subjects requiring treatment with any drug which might interact adversely with or obscure the action of the study medication (e.g., stimulants, sympathomimetics, antidepressants, carbonic anhydrase inhibitors, anti-obesity drugs).

 Subjects who have received psychoactive medication (other than zaleplon [Sonata] or zolpidem [Ambien] -- as needed for restlessness/insomnia) within one week prior to randomization.

 Subjects who have begun and/or are receiving formal psychotherapy (cognitive behavioral therapy, interpersonal therapy, or dietary behavioral therapy) for BED or weight loss within the past 3 months.

 Subjects previously enrolled in this study or have previously been treated with lamotrigine.

 Subjects who have received an experimental drug or used an experimental device within 30 days.


Pathways Linking Reduced Sleep Duration and Quality to Obesity Risk

Summary: This study is designed to study the pathways through which short sleep duration or poor sleep quality can lead to an increased risk of developing diabetes and obesity.
Inclusion criteria: inclusion criteria:

 Normal weight

 Healthy

 Normal sleep times

Exclusion criteria: :

 Sleep disorders

 Overweight

 Diabetes

 Other health conditions

 Excessive caffeine and alcohol intake

 Smoking

['Baseline', 'Sleep restriction', 'Reduced Sleep Quality']

Baseline
Sleep restriction
Reduced Sleep Quality


Impact of Literacy Level on Patient Education and Health Among People With Arthritis

Summary: People with poor literacy may have worse health and less knowledge about how to manage their disease than patients at high reading levels. Patients with arthritis usually receive information on how to manage their disease that is written at an 11th grade reading level. The purpose of this study is to compare the health outcomes of patients with arthritis given either standard 11th grade level materials or interactive, in-person arthritis education along with materials written at a lower reading level.
Inclusion criteria: inclusion criteria:

 Native English speaker

 Patient at the Rheumatology Clinic at Brigham and Women's Hospital, Boston, Massachusetts

 Diagnosis of rheumatoid arthritis, psoriatic arthritis, or seronegative polyarthritis
Exclusion criteria:

['11th grade reading level arthritis materials', 'Interactive in-person arthritis education']

['Rheumatoid Arthritis', 'Psoriatic Arthritis', 'Polyarthritis']

Rheumatoid Arthritis
Psoriatic Arthritis
Polyarthritis


A Study of Nitazoxanide in Patients With AIDS and Diarrhea Caused by Cryptosporidium

Summary: To determine the frequency of complete, marked, and partial clinical responses in patients with cryptosporidiosis treated with 6 weeks of NTZ versus 21 days of placebo. To determine the safety of NTZ in subjects with cryptosporidiosis.~There is no proven therapy for cryptosporidiosis in persons with AIDS. Nitazoxanide appears to be a good candidate drug for further evaluation because of its effectiveness in preclinical models, the data from early clinical trials and its safety profile. Cooperation between clinical researchers and basic scientists in clinical trials of agents for HIV infection and its complications is a high priority for the ACTG, the NIAID, and the NIH. Thus, it is important to design a clinical trial of NTZ that includes cooperation with basic scientists.
Inclusion criteria: inclusion criteria

 Patients must have:

 Documented HIV infection.

 Intestinal cryptosporidiosis.

 Willingness to undergo a 1 week washout phase of all anticryptosporidial medications and stabilization on a protocol directed, antidiarrheal regimen.

 Greater than or equal to 4 stools per day, on average, for a minimum of 21 out of 28 days prior to study entry, secondary to cryptosporidiosis.

 AS PER AMENDMENT 2/10/97:

 Four or more stools per day, on average, during the 5-day screening period prior to baseline.

Exclusion criteria:

 Co-existing Condition:

 Patients with the following symptoms and conditions are excluded:

 Inability to tolerate oral medications.

 Life expectancy less than 3 months in the opinion of the investigator.

 Active CMV colitis, C. difficile colitis, giardiasis, salmonellosis, shigellosis, campylobacteriosis, inflammatory bowel disease, diarrhea secondary to another documented intestinal pathogen, or active or uncontrolled MAC disease, defined as symptomatic MAC disease and/or a patient who is not on appropriate anti-MAC therapy in the presence of MAC disease.

 NOTE:

 Patients who have been treated for MAC disease for at least 4 weeks and have resolved their symptoms may be enrolled. Patients dually infected with microsporidiosis may be randomized to the study but will not count toward the sample size.

 AS PER AMENDMENT 2/10/97:

 Failure to record a minimum of four days of information on the use of antidiarrheal medication and the frequency of bowel movements in the daily diary during the screening period.

 Allergy to corn or corn products.

 Concurrent Medication:

 Excluded:

 Need for continuing use of any medications with putative anticryptosporidial activity, including paromomycin, azithromycin, clarithromycin, spiramycin, bovine colostrum, monoclonal anticryptosporidial antibody preparations, letrazuril, atovaquone, diclazuril, octreotide and albendazole (prohibited during the acute treatment phase for patients dually infected with microsporidiosis)..

 NOTE:

 Patients who develop cryptosporidiosis while taking azithromycin or clarithromycin may be enrolled as long as they have been taking those medications for at least four weeks and remain on a stable dosage.

 All antidiarrheals that are not part of the protocol directed Antidiarrheal Stabilization Regimen.

 The addition of any new antiretroviral agent or immunomodulator therapy the first 63 days on the study.

 Prior Medication:

 Excluded:

 Treatment at any time prior with nitazoxanide.

 Addition of any new antiretroviral or increase in the dosage or current antiretrovirals within 4 weeks to study entry.


Prophylaxis With Single Versus Five Dose of Antibiotic Therapy as Treatment of Patients With Gangrenous Acute Appendicitis

Summary: A prospective, randomized controlled clinical trial was conducted at the Hospital Universitario de Santander to test the effectiveness of providing a single 1-dose therapy of antibiotic prophylaxis versus a 5-day antibiotic therapy in patients with acute gangrenous appendicitis.
Inclusion criteria: inclusion criteria:

 patients with diagnosis of acute appendicitis with intraoperative finding of a gangrenous appendix who accepted to enter the study

Exclusion criteria: :

 patients under 12 or older 65 years old

 Patients with possible immunosuppression such as diabetes, cancer, kidney failure, liver failure

 Pregnancy

 Patients who have received antibiotic treatment within seven days before surgery

 Patients difficult to monitor or follow up


A Trial of Anti-TNF Chimeric Monoclonal Antibody (cA2) in Korean Patients With Active Rheumatoid Arthritis Despite Methorexate (Extension Part)(Study P05645)(COMPLETED)

Summary: This trial is extension part of the P04280 (placebo-controlled, double-blind, randomized study of chronic treatment with infliximab in approximately 140 patients, NCT00202852). This study will be conducted at 6 study centers in South Korea. After completion of the last follow-up visit at Week 30 and code break in main double-blind trial, subjects randomized to the placebo group and those who were treated with an infliximab-containing regimen who maintained clinical response at the time of study completion will be provided with open-label infliximab for treatment of their conditions and additional safety data will be collected.
Inclusion criteria: inclusion criteria:

 Patients received placebo in main double-blind study (P04280, NCT00202852)

 Patients received Infliximab-containing regimen showing clinical response at week 30 in main double-blind study (P04280)

 [Main double-blind study (P04280, NCT00202852) inclusion criteria]

 Diagnosis of rheumatoid arthritis (RA) according to the revised 1987 criteria of the American Rheumatism Association (Arnett et al, 1988). The disease should have been diagnosed >6 months prior to screening.

 Active disease at the time of screening and pre-infusion as defined by:

 >=6 swollen joints

 >=6 tender joints and

 2 of the following:

 morning stiffness >=45 min

 erythrocyte sedimentation rate (ESR) >=28 mm/h

 C-reactive protein (CRP) >=20 mg/L

 Men and women, >=18 to <=75 years of age

 Men and women of childbearing potential must be using adequate birth control measures (abstinence, oral contraceptives, intrauterine device (IUD), barrier method with spermicide, or surgical sterilization) and should continue such precautions for 6 months after receiving the last infusion.

 Must have been using oral or parenteral MTX for >3 months with no break(s) in treatment of >2 weeks total during this period. Patients must have been on a stable dose of >=12.5 mg/wk (maximum 20 mg/wk) for at >4 weeks prior to screening.

 Must be on a stable dose of folic acid prophylaxis for >4 weeks prior to screening.

 Patients using oral corticosteroids, must have been on a stable dose of <=10 mg/day for >4 weeks prior to screening. If currently not using corticosteroids the patient must have not received corticosteroids for >4 weeks prior to screening.

 If using nonsteroidal anti-inflammatory drugs (NSAIDs), patients should have been on a stable dose for >4 weeks prior to screening.

 The screening laboratory tests must meet the following criteria:

 Hemoglobin >=5.3 mmol/L (>=8.5 g/dL), providing a low hemoglobin level is not due to nutritional deficiencies or due to diseases other than chronic RA

 white blood cell (WBC) >=3.5 x 10^9/L (>=3.5 x 10^3/mm^3)

 Neutrophils >=1.5 x 10^9/L (>=1.5 x 103/mm^3)

 Platelets >=100 x 10^9/L (>=100 x 103/mm^3)

 Serum transaminase <=2 times the upper limit of normal

 Alkaline phosphatase levels <=2 times the upper limit of normal

 Serum creatinine <=150 µmol/L (<=1.7 mg/dL)

 Must be able to adhere to the study visit schedule and other protocol requirements.

 Must be capable of giving informed consent and the consent must have been obtained prior to any study procedures including wash-out period.

Exclusion criteria: :


A Comparison of Certoparin and Unfractionated Heparin in the Prevention of Thromboembolic Events in Acutely Ill Medical Patients

Summary: This study is designed to provide efficacy and safety data for certoparin in the prophylaxis of venous thromboembolism in immobilized, acutely ill medical patients.
Inclusion criteria: inclusion criteria:

 Hospitalized medical patients 70 years of age or older

 Acute medical illness with significant decrease in mobility expected for at least 4 days (patient bedridden or only able to walk short distances)

 written informed consent

Exclusion criteria: :

 immobilization longer than 3 days prior to randomization

 prior major surgery, trauma or invasive procedure within the last 4 weeks including any injuries or operation of central nervous system

 expected major surgical or invasive procedure within the next 3 weeks after randomization

 LMWH/heparin administration longer than 48 hours in the 5 days prior to randomization

 immobilization due to cast or fracture

 indication for anticoagulatory or thrombolytic therapy

 acute symptomatic DVT / PE

 known hypersensitivity to any of the study drugs or drugs with similar chemical structures

 Acute or history of heparin induced thrombocytopenia type II (HIT II)

 Other protocol-defined inclusion/


The Therapeutic Role of Intravenous Albumin Administration for Peptic Ulcer Bleeding Patients With Hypoalbuminemia

Summary: To test whether intravenous albumin can decrease the rebleeding rate or shorten the duration of hospitalization in patients with peptic ulcer bleeding and hypoalbuminemia.
Inclusion criteria: inclusion criteria:

 Clinical presentations of melena, hematochezia, or hematemesis

 Gastroscopy confirmed peptic ulcers and major stigmata of recent hemorrhage

 A Rockal score ≥ 6

Exclusion criteria: :

 Gastric or esophageal, or duodenal tumor bleeding

 Ulcer due to mechanical factors

 Warfarin use

 Failure to establish hemostasis under gastroscopy

 Hypersensitivity to omeprazole, esomeprazole, albumin or any component of the formulation.

['Peptic Ulcer Bleeding', 'Hypoalbuminemia']


Evaluation of a Diagnostic Feature in a Cardiac Resynchronization Therapy (CRT) Device

Summary: The purpose of this study is to evaluate the performance of a new sensor-based diagnostic feature, which has been implemented in a cardiac resynchronization therapy (CRT) device. This trial will study the effectiveness of the diagnostic feature to detect heart failure events in medically stable, ICD-indicated, congestive heart failure patients.
Inclusion criteria: inclusion criteria:

 Subject eligible for implantation of a CRT-D device according to current available guidelines for cardiac resynchronization therapy

 Subject has severe heart failure (NYHA Class III or IV)

 Subject has experienced at least one heart failure event within six months prior to enrollment

 Subject continues to have heart failure symptoms despite receiving optimal medical therapy

 Schedule for implant of a PARADYM CRT-D (Model 8770)

 Subject has signed and dated an informed consent form

Exclusion criteria: :

 Any contraindication for standard cardiac pacing

 Any contraindication for ICD therapy

 Abdominal implantation site

 Hypertrophic or obstructive cardiomyopathy

 Acute myocarditis

 Unstable coronary symptoms (unstable angina or myocardial infarction) within the last month

 Recent (within the last month) or planned cardiac revascularization or coronary angioplasty

 Correctable valvular disease that is the primary cause of heart failure

 Mechanical tricuspid valve

 Receiving continuous intra-venous infusion of positive inotropic therapy or intermittent therapy (intravenous infusion) more than twice per week

 Heart transplant recipient

 Renal insufficiency requiring dialysis

 Already included in another clinical study

 Life expectancy less than 12 months

 Inability to understand the purpose of the study or refusal to cooperate

 Inability or refusal to provide informed consent or HIPAA

 Unavailability for scheduled follow-up at the implanting center

 Known sensitivity to 1mg dexamethasone sodium phosphate (DSP)

 Under guardianship

 Age of less than 18 years

 Pregnancy

['Paradym CRT + Physiological Diagnosis (PhD)']


Draining PLN and Synovial Inflammation in RA Knee Joints Pre and Post Anti-TNF or B Cell Depletion Therapy

Summary: The purpose of this study is to examine the effect of anti-TNF therapy on rheumatoid arthritis using magnetic resonance imaging (MRI) and ultrasound imaging.~Anti-TNF therapies include a group of medications such as Enbrel, Remicade and Humira that affect your body's inflammatory response. These medications are routinely prescribed for the treatment of rheumatoid arthritis.
Inclusion criteria: inclusion criteria

 Signed, IRB-approved, written informed consent

 Subjects can be of either gender but must be more than 18 years old.

 Subjects must fulfill the disease activity criteria for RA and a DAS28 will be assessed at baseline and at 2 months after rituximab therapy.

 Aim A - Eligible subjects must meet criteria for RA and have an inadequate response to MTX defined as DAS28 >5.1. They must have been on a steady dose of MTX (between 15 and 20 mg /week for a minimum of 8 weeks). Subjects must have evidence of knee synovitis on exam to enter the study.

 Aim B - Subjects must have demonstrated a response to a TNF antagonist as evidenced by a DAS score <2.8 or <4 tender and swollen joints. Flare will be defined as a DAS 28 >5.1 of more than 8 swollen and tender joints. Subjects must have evidence of knee synovitis to enter the study. Subjects will be off etanercept, infliximab or adalimumab for 4 weeks before starting BCDT. All subjects must also be on a stable dose of DMARD (MTX, leflunomide, azulfidine, hydroxychloroquine) for 8 weeks before entry into the study.

Exclusion criteria:

 Patients will be excluded for medical or other reasons at the discretion of the investigators. The reasons for the exclusion must be recorded, e.g. risk of non-compliance, vulnerability, medically unstable, etc.

 Active systemic disorders or inflammatory conditions (i.e., chronic infection with hepatitis B, hepatitis C or HIV) other than the conditions being studied.

 Patients with a plasma creatinine > 1.5 mg/dl

 Aim B - Subjects with an allergy to corticosteroids will be excluded from the study.

 Anyone answering yes to the following questions will be excluded:

 Do you have a history of:

 Cardiac (Heart) pacemaker or defibrillator?

 Cardiac (Heart) valve replacement or prosthesis?

 Aneurysm clips from brain surgery?

 Ear prosthesis (cochlear or stapedial implant)? (hearing aids?)

 Neurostimulator?

 Biostimulator?

 Any type of pumps in or on your body?

 Shrapnel, gunshot wound, BB pellet?

 Metallic penile prosthesis?

 Metallic blood vessel filter or stent?

 Orthopedic prosthesis?

 Have you ever had an injury involving metal fragments in your eye?

 Have you ever had neurosurgery (brain or skull surgery)?

 Note: Subjects treated with rituximab will not be excluded from study based on their immunosuppressive drugs but use of these agents will be recorded and discussed in the analysis.


Immune Response After Booster Vaccination in HIV - Infected Patients Who Received Rabies Primary Vaccination

Summary: Booster rabies vaccination in HIV - infected patients who have ever received rabies primary vaccination could improve their immune response to this kind of vaccine.
Inclusion criteria: inclusion criteria:

 HIV infected patients 18-60 years of age

 Ever received primary rabies immunization

Exclusion criteria: :

 currently have any active opportunistic infections

 have received blood or blood product within previous 3 months

 history of allergy to vaccine or any vaccine components

 currently received anti-malarial drugs


ACE Stapler Sub Study

Summary: Obesity and its associated conditions have reached epidemic proportions. Estimates are that about one third of the adults in the United States have obesity. At this moment there are many therapeutic approaches for the treatment of obesity. But, efficacy of most treatment options are limited and so far surgical intervention has been proven to be the only strategy to overcome severe obesity. However, bariatric surgery has limitations and risks, which might be minimized by non-incisional endoscopic procedures.~BaroSense developed a new device, called the Articulating Circular Endoscopic (ACETM) Stapler, which can be used in the treatment of obesity. It is a trans-oral procedure, which intends to reduce the ability of the stomach to expand by creating plications in the region of the fundus and greater curvature. In contrast with other bariatric surgery it is endoscopically performed, reversible and if it fails most future surgical options are still open.~The main study ('Open, prospective study to evaluate the safety and preliminary effectiveness of the BaroSense ACE™ Stapler for the treatment of obesity', multicenter study (MUMC+, AMC and St. Antonius), accepted by MEC AMC) seeks to determine the safety and efficacy of this plicating system for patients with severe obesity.~In this sub-study the investogators want to unravel the exact mechanism and provide more information about the efficacy of the BaroSense ACE™ Stapler. Therefore the authors will measure changes in various parameters that are known to affect weight loss and metabolism, before and after gastric plication (by using the BaroSense ACE™ Stapler) in overweight subjects (these parameters will only be measured in patients at MUMC+). These parameters are post-prandial satiety, food-reward and related brain signalling, gastric emptying, behaviour towards food, food intake, satiety hormone release, microbiota composition and inflammatory markers.~Objectives:~Aim of the present study will be to assess the effect of the BaroSense ACE™ stapler on postprandial satiety, food-reward and related brain signalling, gastric emptying, behaviour towards food, food intake, hormone release, microbiota composition and inflammatory markers.
Inclusion criteria: inclusion criteria:

 Criteria for inclusion in main ACE stapling study:

 Subject must be able to understand and be willing to sign an informed consent document.

 Subject must be willing and able to participate in all aspects of the study and agree to comply with all study requirements for the duration of the study. This includes availability of reliable transportation and sufficient time to attend all follow-up visits.

 Subject has a BMI of 40 - 45 or 30 to 39.9 plus one or more co-morbid diseases expected to improve with weight loss, including but not limited to hypertension, dyslipidemia, obstructive sleep apnea, or diabetes mellitus.

 Subject must be fully ambulatory, without chronic reliance on walking aids such as crutches, walkers or a wheelchair.

 Subject must be of sufficient and stable medical health, as evaluated by the Principal Investigator.

 Subject must have a primary care physician that will manage the subject for any co-morbid conditions throughout the study.

 Subject must have failed standard obesity therapy of diet, exercise, behaviour modification, and pharmacologic agents either alone or in combination, as assessed by an interview with a member of the study team at baseline.

 Subject agrees to refrain from any type of reconstructive surgery that may affect body weight such as mammoplasty or abdominal lipoplasty or liposuction, during the trial.

 inclusion criteria sub study

 • Patient must be included in the main study

Exclusion criteria: :

 Main study

 Subject has history of/or signs and/or symptoms of gastro-duodenal ulcer disease.

 Subject has poorly controlled diabetes as indicated by the lack of stable diabetes medications and doses over the last month, or has a history of diabetes for greater than 10 years.

 Subject has had significant weight loss in the last 3 months, or between baseline and the study procedure.

 Subject has a history or is diagnosed with eating disorders.

 Subject has history of peptic ulcer and tests positive for H. pylori, unless treated before the procedure.

 Subject has symptomatic congestive heart failure, cardiac arrhythmia or unstable coronary artery disease.

 Subject has pre-existing respiratory disease such as chronic obstructive pulmonary disease (COPD), pneumonia or cancer.

 Subject has significant esophageal disease including Zenker's diverticulum, grade 3-4 reflux esophagitis, stricture, Barrett's esophagus, esophageal cancer, esophageal diverticulum, dysphagia, achalasia, or symptoms of dysmotility.

 Subject is observed during EGD to have heavily scarred, malignant or poor quality/friable tissue in areas of the stomach where plications are to be placed.

 Subject has renal and/or hepatic insufficiency.

 Subject has thyroid disease which is not controlled with medication.

 Subject has a history of intestinal strictures or adhesions.

 Subject has systemic infection in the body at the time of the plication procedure.

 Female subject who is pregnant (i.e., has a positive urine or blood pregnancy test prior to the procedure), is suspected to be pregnant, is lactating or is of childbearing potential but refuses to use adequate contraception during the study.

 Female subject who started birth control pills less than 3 months before enrollment, or who plans to start taking birth control pills during the study.

 Subject has had previous bariatric, gastric or esophageal surgery; intestinal obstruction; portal gastropathy; gastrointestinal tumors; esophageal or gastric varices, or gastroparesis.

 Subject has severe coagulopathy (prothrombin time > 3 seconds over control or platelet count < 100,000) or is presently taking heparin, coumadin, warfarin, or other anticoagulants or other medications which impede coagulation or platelet aggregation.

 Subject has chronic/acute upper GI bleeding conditions.

 Subjects who are unable to discontinue use of aspirin and/or non-steroidal anti-inflammatory agents (NSAIDs) at least 14 days prior to a plication procedure and continuing for 14 days post-procedure.

 Subjects undergoing chronic steroid therapy.

 Subjects undergoing immunosuppressive therapy.

 Subjects who cannot discontinue either prescription or over the counter weight loss medications for at least 30 days prior to the procedure as well as during the trial period.

 Subjects who have started medications within the last 3 months that are known to cause weight gain.

 Subjects who have cardiac pacemakers or other electronic implantable devices.

 Subjects who have hiatal hernias greater than 2 cm.

 Subjects who have current or potential neck masses that in the opinion of the investigator, may interfere with study-related procedures, or has a Mallampati (intubation) score greater than 3.

 Subjects who have poorly controlled psychiatric disease including but not limited to manic-depressive disorder, schizophrenia, borderline personality disorder, depression or suicidal tendencies.

 Subject has Crohn's disease or Ulcerative Colitis.

 Subject currently uses or has a history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day).

 Subject has participated in a clinical study with an investigational new drug, biological, or therapeutic device within ≤ 28 days prior to enrollment in this study, and does not agree to abstain from participation in other clinical trials of any kind during this study.


Study of Weekly Paclitaxel, Carboplatin and Irinotecan to Treat Lung Cancer

Summary: Evaluate the efficacy and toxicity of the weekly combination chemotherapy of Paclitaxel, Carboplatin and Irinotecan in Stage IIIb and IV NSCLC with malignant pleural effusion
Inclusion criteria: inclusion criteria:

 Histological or cytological diagnosis of non-small cell lung cancer.

 Malignant pleural effusion proven by cytological examination.

 Patient must have stage IIIB or IV disease with malignant pleural effusion.

 We plan to recruit 16 patients who have smoked cigarettes of at least 20 pack per year, 16 patients who do not smoke but have been exposed to second hand smoking by living with a person who has smoked 20 pack per year cigarette in the same household and 16 patients who are non-smokers (never smoked) and no second hand smoking exposure in the same household. The accrual will be stopped once the number of patients is reached in each group.

 ECOG PS 0, 1 or 2.

 Measurable disease (in addition to malignant pleural effusion).

 No prior chemotherapy for metastatic or recurrent disease. Patient may have surgery or radiation or combined chemoradiation, or neoadjuvant chemotherapy at primary diagnosis. This kind of chemotherapy will not be counted as patient has had prior chemotherapy for metastatic or recurrent NSCLC.

 WBC > 3500/uL and ANC > 2,000/uL, platelet > 100,000/uL AST/ALT < 3 X UNL, bilirubin < 1.5 mg/dL ( or < 35 uM), creatinine < 1.5 mg/dL (or < 125uM for men and 90uM for women).

 Age > 18

 No history of congestive heart failure, myocardial infarction or life-threatening arrhythmia (such as ventricular tachycardia, supraventricular tachycardia, brachycardia < 40/min or atrial fibrillation or flutter with ventricular rate > 150/min) within 6 months of entry.

 Signed informed consent

 Negative mammogram and ovaries examination by CT scans and no history of breast cancer or ovarian cancer in female patients.

 Negative pregnancy test in female menstruating patient within one week of starting chemotherapy and use of effective contraceptive methods during study.

 Patients with brain metastasis will be eligible provided their neurological abnormality is stable or improved after whole brain radiation, stereostatic radiosurgery or gamma knife treatment and/or dexamethasone for 3 weeks and patients fulfil all other eligibility criteria.

Exclusion criteria: :

 ECOG performance status 3 or worse.

 Any prior chemotherapy regimen for metastatic or recurrent diseases.

 No measurable disease, even after drainage of pleural effusion.

 ANC < 1,999/uL or Bilirubin > 1.5 mg/dL (or > 35uM)

 Plt < 100,000/uL or

 ALT/AST > 3 x UNL

 Creatinine > 1.5mg/dL (or > 125uM)

 Patient has history of congestive heart failure, myocardial infarction or life-threatening arrhythmia (such as ventricular tachycardia, supraventricular tachycardia, atrial fibrillation/flutter with ventricular rate > 150/min or bradycardia < 40/min) within 6 months before entry.

 Prior history of breast cancer or ovarian cancer in female patients or any cancer except cured cervical carcinoma in-situ or skin cancer.

 Fasting blood sugar > 200 mg/dL (> 14uM) except in patients on dexamethasone for brain metastases.

['Paclitaxel, Carboplatin and Irinotecan']


Study of Optimal Replacement of Thyroxine in the Elderly

Summary: All patients with hypothyroidism are currently treated the same way, regardless of age. The investigators want to look at whether people aged 80 years or older would benefit from being treated with lower doses of levothyroxine. There are three reasons why the investigators think this could be beneficial, but this is not yet proven:~Some older people with hypothyroidism may have few symptoms.~Doctors look at the amount of Thyroid Stimulating Hormone (TSH) in the patient's blood to decide the dose of Thyroxine received. The standard normal TSH range used to determine the dose of levothyroxine is from younger people. The investigators wonder whether this is appropriate to all age ranges particularly as the investigators know that older people may normally have higher TSH values.~If TSH levels are too low there may be a slight increased risk of problems such as brittle bones or an irregular heartbeat.~The best way to test whether older people benefit from lower doses of levothyroxine is by a large clinical trial. Before the investigators can do this, the investigators need to run a smaller clinical trial called a pilot study (SORTED 1) to examine whether this is practical and acceptable. The pilot study aims to recruit 50 patients with hypothyroidism aged 80 or above.~Participants will be randomly allocated to receive their routine or lower dose of levothyroxine. Follow-up will be conducted over approximately 25 weeks.~The investigators also propose a qualitative study (SORTED 2) to specifically understand patient's willingness to take part in a RCT and participant's experience of the intervention.~Finally, the investigators propose a retrospective cohort study of 400 treated hypothyroid patients aged 80 years or more registered in 2008 in Primary Care Practices with the aim of studying outcomes after 4 years. The cohort study will collect data required to inform a sample size calculation for a future full study where the primary outcome will be 4 year mortality.
Inclusion criteria: inclusion criteria:

 Males and Females aged 80 years or older

 Diagnosed with hypothyroidism and treated with Levothyroxine for at least 6 months

 Living independently in the community

 All TSH results within the range 0.4 - 4mU/L in the 3 months before commencing the study

 Participant has provided written informed consent for participation in the study, prior to any study-specific procedures

Exclusion criteria: :

 Established dementia and therefore deemed incapable of providing informed consent.

 Other medical conditions which, inthe opinion of the Chief Investigator, would prevent them from participating in the study (for example, end stage cancer, severe chronic health conditions where the patient is housebound)

 Nursing Homes or Residential Care Home residents

 Individuals with thyroid cancer: since they require high doses of LT4 to suppress their serum TSH

 Individuals on 25 mcg dailty of LT4: dose reduction will mean that they stop thyroid replacement treatment

 Non english speaking individuals

 Participation in any other investigational trials within the last 3 months

 Participants prescribed medications that can affect thyroid function (amiodarone, lithium, carbimazole or propylthiouracil)

 Known or suspected lactose intolerance (this would have implications for the proposed over-encapsulated IMP)


Study to Analyze the Clinical and Cost Impact of Complete and Incomplete Rotavirus (RV) Vaccination

Summary: This study aims to estimate the clinical and cost impact of RV vaccinations (both Rotateq® and Rotarix®) among children aged less than 5 years using insurance claims data from commercial plans and Medicaid low-income population. The impact of incomplete and complete RV vaccination will also be examined, overall and stratified by age (e.g., 6 weeks to 8 months, 8 months and onwards ) and calendar time of RV vaccination (e.g., 2006 onward).
Inclusion criteria: inclusion criteria:

 Continuously enrolled from birth. (Note: Due to the absence of birth dates in insurance claims data, this inclusion criterion will be met if a child's year of first enrollment and year of birth are the same. If so, then the date of first enrollment will be used as proxy for date of birth.)

 Received both medical and pharmacy benefits.

Exclusion criteria: :

 Enrolled in capitation-based health plans.

 For MarketScan Commercial, residence in states with universal vaccination programs that include the RV vaccine or where RV vaccine inclusion cannot be ascertained (i.e., Alaska, Idaho, Massachusetts, Maine, North Dakota, New Hampshire, New Mexico, Oregon, Rhode Island, Vermont, Washington, Wisconsin, and Wyoming).

 Lost to follow-up or had RV prior to 6 weeks of age.


Clinical Validation of Lophius Biosciences Kit T-Track® CMV in Kidney Transplant Recipients

Summary: This study aims to validate whether Lophius Biosciences Kit T-Track® CMV is suitable to assess the functionality of CMV-specific cell-mediated immunity (CMI) and to determine a protective cut-off value for CMV reactivations/disease in kidney transplant recipients.~Lophius kit T-Track® CMV represents a highly standardized and sensitive diagnostic tool to assess the functionality of a network of clinically relevant CMV-reactive effector cells. It is based on the stimulation of peripheral blood mononuclear cells (PBMC) with urea-formulated immunodominant CMV proteins, pp65 and IE-1, and the subsequent quantification of CMV-specific CMI (spot forming colonies) using a highly sensitive IFN-γ ELISpot.
Inclusion criteria: inclusion criteria:

 Patient receiving a kidney graft

 Recipient being CMV-seropositive prior transplantation and receiving a graft from either a CMV-seropositive or from a seronegative donor (intermediate risk groups, D+/R+; D-/R+,)

 Patient scheduled to follow the preemptive antiviral strategy with oral valganciclovir or intravenous ganciclovir after transplantation

 Patient receiving the standard triple immunosuppressive regimen (CNI, MMF/MPA or mTOR inhibitors, steroids), with or without induction therapy (except ATG) as start therapy after transplantation

 Male or female patient at least 18 years of age

 Written informed consent

Exclusion criteria: :

 Patient is scheduled for the optional visit 1, but requires ongoing treatment with a systemic immunosuppressive drug already prior to kidney transplantation (except induction therapy other than ATG)

 Patient receiving ATG as induction therapy

 Patient is known to be positive for HIV or suffering from chronic hepatitis infections

 Patient has significant uncontrolled concomitant infections or other unstable medical conditions before transplantation that could interfere with the study objectives

 Patient is unable to comply with the visit schedule in the protocol

 Patient has any form of substance abuse, psychiatric disorder or condition that, in the opinion of the investigator may invalidate communication with the investigator

['Cytomegalovirus', 'Kidney Transplantation', 'CMV Specific Immune Response']

Cytomegalovirus
Kidney Transplantation
CMV Specific Immune Response


A Study Comparing High Dose Omeprazole Infusion Against Scheduled Second Endoscopy for Bleeding Peptic Ulcer

Summary: A prospective randomized study to compare the adjunctive use of high dose omeprazole infusion against scheduled second endoscopy in prevention of peptic ulcer rebleeding after therapeutic endoscopy.
Inclusion criteria: inclusion criteria:

 all consecutive patients admitted for peptic ulcer bleeding (including bleeding anastomotic ulcers) with emergency endoscopy done in 24 hours after admission with Forrest type Ia, Ib, and IIa, IIb

 age 15 - 90 years

 Written consent available

Exclusion criteria: :

 ulcer bleeding not controlled in first endoscopy

 Bleeding from malignant ulcer or tumor

 Bleeding from Dieulafoy lesion/ angiodysplasia

 Bleeding from injection sclerotherapy ulcer

 Patient with ASA category 5

['Intravenous omeprazole infusion', 'Scheduled second endoscopy']

Intravenous omeprazole infusion
Scheduled second endoscopy


Combivent vs. Salbutamol in Patients With Metacholine Induced Bronchospasm

Summary: The purpose of this study was to evaluate whether 2 puffs of fixed combination of aerosolized 120 mcg salbutamol sulphate (equivalent to 100 mcg of the base) + 20 mcg ipratropium bromide confers significant additional protection against metacholine induced bronchoconstriction in asthmatic atopic patients when compared to 2 puffs of aerosolized 100 mcg salbutamol alone.
Inclusion criteria: inclusion criteria:

 Male or female patients with a diagnosis of asthma according to the American Thoracic Society Criteria

 Patients aged 7 to 12 years inclusive

 Patients able to perform spirometry

 Patients with FEV1 (forced expiratory volume in the first second) ≥ 80% of predicted normal value after saline

 Patients with PD20 (provocative dose that reduces FEV1 by 20 %) metacholine lower than 8 mg/ml

 Patients or responsible relatives willing and able to sign an informed consent form

Exclusion criteria: :

 Patients on treatment for or suspected as having glaucoma

 Patients with known allergy of contra-indications to either salbutamol, ipratropium or their excipients

 Patients suspected on clinical grounds to have pneumonia, pneumothorax or pneumomediastinum

 Patients with a history of chest surgery

 Patients with other respiratory conditions if diagnosed. These include pulmonary fibrosis, bronchiectasis, cystic fibrosis, sarcoidosis, pulmonary tuberculosis, pulmonary complications of AIDS

 Patients requiring drugs for the treatment of the acute asthma attack other than the study drugs or oxygen

 Patients who have been previously recruited into this study

 Patients with myocardiopathy, pulmonary edema or other life threatening diseases, which in the judgement of the pediatrician precludes their entry into the study

 Patients with obvious or previously diagnosed serious hepatic or renal disease

 Patients who have been under the following drugs within the specified periods of time prior to determination of Baseline FEV1 or metacholine challenge

 INHALED:

 Short acting β2 agonists: 6 hours

 Long acting β2 agonists: 12 hours

 Ipratropium bromide: 8 hours

 DSCG (disodium cromoglicate): 7 days

 Nedocromil: 7 days

 ORAL:

 Short acting β2 agonists: 18 hours

 Anticholinergics: 7 days

 Short acting theophylline: 24 hours

 Long acting theophylline: 72 hours

 Antihistamines: 7 days

 Astemizole: 3 months

 Ketotifen: 3 months

 INHALED or ORAL: Other investigational drugs: 3 months

 INHALED or ORAL: Corticosteroids: 30 days

['Salbutamol sulfate/Ipratropium bromide', 'Salbutamol']

Salbutamol sulfate/Ipratropium bromide
Salbutamol


Exhaled NO Testing in Filariasis

Summary: This study is looking at the difference in exhaled nitric oxide levels in patients with and without laboratory evidence of filariasis.
Inclusion criteria: inclusion criteria:

 Age 6 years or older of either gender

 Patients presenting with pulmonary symptoms a. Confirmed or suspected asthma patients: i. Patients presenting with symptoms consistent with an acute exacerbation of asthma, including:

 1. Wheezing 2. Shortness of breath 3. Chest tightness 4. Cough ii. Disposition to the asthma room after triage and physician evaluation (disposition to other areas of the A&E allowed if due to no available space in the asthma room) iii. Patients are potentially eligible with or without a past history of health care provider diagnosed asthma iv. Patients are potentially eligible regardless of the number of previous episodes of wheezing (i.e. patients with a first episode of bronchospasm are potentially eligible) v. If suspected or documented to have pneumonia or a pulmonary infiltrate, patients are potentially eligible if:

 They have a dry cough (no production of purulent sputum)

 They have bronchospasm as manifested by wheezing or need for salbutamol (albuterol) breathing treatments vi. Patients with wheezing are not eligible if they:

 1. Have purulent sputum production 2. Have known or suspected:

 a. Tuberculosis b. Immunodeficiency c. Congestive heart failure d. Foreign body aspiration b. Patients presenting with a chief complaint of cough: i. Potentially eligible patients will have a cough of greater than one week (seven days) duration ii. Asthma room disposition is not required for these subjects iii. If suspected or documented to have pneumonia or a pulmonary infiltrate, patients are potentially eligible if:

 1. They have a dry cough (no production of purulent sputum) iv. Patients with cough are not eligible if:

 Have purulent sputum production

 Have known or suspected:

 Tuberculosis

 Immunodeficiency

 Congestive heart failure

 Foreign body aspiration

 Patients will be medically stable at the time of the consent process (see
Exclusion criteria:  below)

 A minimum of 2 years of continuous residence in Guyana at the time of enrollment, exclusive of short trips out of the country (at least 21 of previous 24 months physically in Guyana)

 English speaking


Comparison of Intravenous Injection of Calcium Antagonist and Beta-blockade on Endothelial Shear Stress of Coronary Artery

Summary: Both calcium channel antagonist and beta-blocker have cardioprotective effect. Endothelial shear stress is predictive factor of clinical outcomes in patients with obstructive stenosis.~The present study aims at comparing the re-distribution of shear stress and blood velocity during whole cardiac cycle after trans-coronary injection of Nicardipine and esmolol.
Inclusion criteria: inclusion criteria:

 Diagnosis of unstable angina and non-Q wave myocardial infarction

 Age 18-75 yr.

 Diameter stenosis of coronary artery<70% diameter stenosis by visual estimation

 Blood pressure >110/70 mmHg

 Heart rate 60-

 100 bpm, No cardiac arrhythmias

Exclusion criteria: :

 St-elevation myocardial infarction

 Lower blood pressure(<100/70mmHg)

 Heart rate <60 or >100 bpm, The presence of cardiac arrhythmias

 Allergy to study drugs

 Women in pregnancy

 Liver dysfunction

 Creatinine >2.5mg/dl

 Bleeding stroke within 6 months

 Left ventricular ejection fraction<30% before maximal medication

['Acute Coronary Syndrome', 'Coronary Artery Disease']

Acute Coronary Syndrome
Coronary Artery Disease


Improving Antibiotic Use in Hospitalized Patients With Pneumonia

Summary: The purpose of the study is to determine whether an antimicrobial stewardship program can decrease the length of hospital stay for patients with pneumonia. The antimicrobial stewardship program is run by a pharmacist and doctor with extensive training in managing infectious diseases. These two health care professionals are responsible for reviewing the records of patients admitted to hospital with pneumonia, and then making specific recommendations to the patient's attending physician about how to manage antibiotic treatment. These recommendations might include discontinuing the antibiotic, or changing the way antibiotics are delivered from intravenous form to pill form, among many other potential options. The attending physician considers whether these recommendations should be followed or rejected. The study has a control group of patients who are not reviewed by the antimicrobial stewardship team, and their length of hospital stay will be compared to the reviewed group of patients. Any differences between these two groups will be assumed to be due to the impact of the antimicrobial stewardship program. So far, no previous study has been able to demonstrate that an antimicrobial stewardship program can reduce the length of stay of patients admitted to hospital with pneumonia. This study has some important differences from previous studies that may make its conclusions more accurately reflect the true impact of antimicrobial stewardship programs. The most important difference is how the timing of the review is modelled in the analysis of the study results. Because the timing of the review varies between patients, with some patients being reviewed at earlier and some at later times, this subtle difference, if not accounted for in the analysis, can mask a true positive effect of the program on length of stay. The investigators study will account for this variation.
Inclusion criteria: inclusion criteria:

 have a positive Febrile Respiratory Illness (FRI) screen on admission to hospital (http://www.health.gov.on.ca/fr/public/programs/emu/sars/reports/dir_122303_acute_care_nonoutbreak.pdf)

 diagnosed with pneumonia by the admitting physician (Acute exacerbations of chronic obstructive lung disease are considered within the definition of pneumonia for the purposes of this study as they are commonly treated with the same antimicrobial regimens as patients with pneumonia)

 admitted to a medical ward

Exclusion criteria: :

 hospitalized for ≥ 48 consecutive hours in the preceding 3 months

 receiving immunosuppressants [defined as ≥ 40 mg prednisone daily (or steroid equivalent) for ≥ 2 weeks preceding hospitalization OR any other immunosuppressant used for systemic illness OR to prevent transplant rejection]

 neutropenic [defined as a polymorphonuclear count ≤ 0.5 x 109 cells/L] from any cause

 immunocompromised [defined as having leukemia, lymphoma, HIV with CD4 cell count ≤ 200, splenectomy or on cytotoxic chemotherapy]

 admitted to high acuity units such as intensive care units

 require mechanical ventilation, either non-invasive or invasive

 have a life expectancy of ≤ 3 months (palliative)