Combination Treatment of S-1 With Paclitaxel in Advanced Esophageal Cancer

Summary: Esophageal cancer is one of the common malignant disease, especially in China. The annual incidence of esophageal squamous cell carcinoma is 260,000 with the motility of 210,000. The prognosis of esophageal cancer is very poor. About 50% of patients have advanced disease at diagnosis and the natural course is only 6-8 months with a 5-year survival rate of 5-7%. Though some patients received surgical treatment, disease will recurrent and metastasis in nearly 90% of the patients.~In past decades, there isn't much improvement of the outcome and survival of advanced esophageal cancer due to the lack of effective chemotherapy agents. The traditional chemotherapy drugs include 5-fluorouracil and cisplatin and the combination of them results in a 25-35% response rate in both first-line and palliative treatment. Paclitaxel plus cisplatin regiment is another promising treatment of esophageal cancer and have been proved effective in many studies. One of our previous study showed paclitaxel and cisplatin treatment resulted in encouraging response rate with manageable side-effects in 131 patients of advanced esophageal cancer.~However, the toxicities of paclitaxel and cisplatin limit their combination in clinic. For example, the polyoxyethylene castor oil paclitaxel could induce acute hypersensitivity reactions and neurotoxicity. Cisplatin could result in dysfunction of kidney and neurotoxicity. In addition, most of esophageal cancer patients are age 65 to 70. Many of them have simultaneously other diseases such as hypertension, diabetes, and chronic kidney disease which cause varying damages of renal function and limit the use of cisplatin in these patients. Therefore, it is urgent for doctors to seek an alternative of cisplatin in the combination chemotherapy treatment.~Therefore, the investigators designed this randomized clinical trial in which a novel combination of S-1 with paclitaxel is used to treat advanced esophageal cancer patients in compare with paclitaxel/cisplatin and 5-FU/cisplatin treatment to explore its efficacy and toxicity. The investigators hope this study will provide some clues for the treatment of esophageal cancer patients.
Inclusion criteria: inclusion criteria:

 Patients who have histologically confirmed diagnosis of esophageal cancer without prior palliative treatment or an interval of at least 6 months from the last operation, adjuvant radiation therapy and adjuvant chemotherapy. If patients received adjuvant chemotherapy, paclitaxel and cisplatin must be excluded from the regiment or the total dosage of cisplatin must be less than 300mg/m2.

 - Patients must be 18 to 75 years old and both genders are eligible.

 - Patients must have measurable or evaluable disease with at least one tumor mass maximum diameter ≥10mm by multi-slice spiral CT or MR scan. If ordinary CT scan is used the tumor mass maximum diameter must ≥ 2cm. Imaging exam must be performed within 15 days from enrollment.

 - Patients must have an expected life expectancy of ≥ 3 months

 - Patients must have a performance status of ≥ 80 on the Karnofsky scale

 - Patients must have normal marrow function and the blood tests must be collected within 7 days from enrollment with a hemoglobin (HGB) of ≥90g/L, an white blood cell (WBC) counts of ≥4.0×109/L，a neutrophil count of ≥2.0×109/L, , a platelet count of ≥100×109/L, a total bilirubin (TBil) of ≤1.0 upper normal limitation (UNL), a creatinine (Cr) of ≤ 1.0 UNL, alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL, Alkaline phosphatase (AKP) ≤5.0 UNL. For patients with liver metastasis, the ASAT/ALAT must be ≤5.0 UNL.

 - Patients must have normal electrocardiogram results and no history of congestive heart failure.

 - Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events.

 - Patients must give written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors

Exclusion criteria: :

 Patients who have received prior palliative treatment or less than 6 months from the last operation, adjuvant radiotherapy, adjuvant chemotherapy.

 Previous treatment regiment involve paclitaxel and S-1

 Tumor mass >10mm by CT or MR scan. The total area of metastatic tumor lesions in liver is over 50% of whole liver or the total area of metastatic tumor lesions in lung is over 25% of whole lung.

 Patients without measurable or evaluable disease, for example cavity effusion or diffusive metastasis of organs.

 Patients with history of other tumors except for those of cervical carcinoma in situ or skin basal cell carcinoma who had been completely treated and without relapse in last 5 years.

 Patients with serious diseases such as congestive heart failure, uncontrolled myocardial infarction and arrhythmia, liver failure and renal failure.

 Patients with only brain metastasis or bone metastasis

 Patients with chronic diarrhea

 Patients with neurological or psychiatric abnormalities including metastasis of the central nervous system that affect cognitive.

 Pregnant or lactated women (premenopausal women must give urine pregnancy test before enrollment).

['S-1 and Paclitaxel', 'Paclitaxel and Cisplatin', '5-FU and Cisplatin']

S-1 and Paclitaxel
Paclitaxel and Cisplatin
5-FU and Cisplatin


The Regain of Gastrointestinal Motility After General Anaesthesia Versus Spinal Anaesthesia in Caesarean Section

Summary: This study aims to compare the time to regain intestinal motility after general anesthesia versus spinal anesthesia for cesarean section.~A double blinded randomized controlled trial was conducted at the Department of Obstetrics and Gynecology, Kasr El-Aini Teaching Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt, between July 20 and November 20, 2015. In the study hospital, the total number of deliveries in 2012 was 15 167, 6244 (41.2%) of which were by cesarean; in 2013, the total number of deliveries was 16 057, 5200 (32.4%) of which were by cesarean.
Inclusion criteria: inclusion criteria:

 Patients set for planned cesarean section under general or spinal anesthesia:

 age from 18 to 37 years.

 Full term(37-41 weeks).

 Singleton pregnancy.

 Hemoglobin level more than 11 gm/dl.

Exclusion criteria: :

 Contraindication to regional anesthesia i.e(patient refusal,coagulopathy,significant hypovolemia,systemic or local sepsis,increased intracranial pressure,severe stenotic valvular heart disease,pre existing neurologic conditions and local anesthetic or fentanyl allergy.

 High risk pregnancies as pre eclampsia,eclampsia,any medical disorder(DM,cardiac and thyroid diseases).

 Previous intestinal surgery,previous C.S. and previous gynecological operations.

['G.I.T. Motility After General Versus Spinal Anaesthesia']


Modafinil Versus Placebo for Hypoactive Delirium in the Critically Ill

Summary: This is a randomized, double-blind, placebo controlled study of 30 patients. Patients who qualify, as per the inclusion criteria (RASS greater than -3, less then +1, CAM positive, present gastric access) will either be given 200mg of modafinil or an identical, indistinguishable placebo. The placebo and study drug will be distributed by the hospital pharmacy. Once enrolled, each patient will be reassessed every morning to determine appropriateness for drug administration. If the RASS is less than -3 (i.e. comatose) or greater then 0 modafinil will not be given. He/she will then be assessed each morning thereafter. Due to the stimulant-like actions of modafinil, the drug will be administered only in the morning. Patients will be assessed for delirium at least twice a day; trained personnel using the Confusion Assessment Method (CAM) will do the assessment. Qualification for a delirium free day will be no positive CAM screens for 24 hours following drug administration. Additional data such as days on mechanical ventilation and progression to tracheotomy will also be collected hypothesizing that patients who take modafinil will have a shorter time to extubation therefore avoiding the need for a tracheotomy. Post-discharge from the unit, but within 48 hours, patients will be asked to participate in a survey (The Richards-Campbell Sleep Questionnaire (RCSQ) assessing their perception of daytime and nighttime sleepiness in the intensive care unit as well as their overall perception of rest. Their functional capacity will also be evaluated at this time and compared to their pre-morbid baseline. The hypothesis tested is that Modafinil restores sleep cycle synchrony in the ICU therefore increasing delirium free days and improving ICU outcomes.
Inclusion criteria: inclusion criteria

 Adult patients ≥ 18 yrs of age, < 76 yrs of age

 Admitted to MICU (3B and 3C) or SICU (8C, 8D, 11C)

 Surrogate present to provide informed consent when patient is not able

 RASS score of >-3, < +1

 CAM positive

 Enteral access

Exclusion criteria: :

 Recent MI (within past 2 weeks)

 High risk of dysrhythmias (i.e. bundle branch block, QT prolongation, class IV HF, implanted device)

 Unable to tolerate enteric medication

 History of stimulant induced mania/psychosis

 Pre-existing neurologic disease

 Patients transferred from outside hospital

 Pregnancy

 Alcohol withdrawal

 History of end stage liver disease (Childs-Pugh class B or worse)

 Prognosis considered hopeless (CMO)


Treatment of Acute Migraine Headache in Children

Summary: Migraine is common in children and is one of the most common etiologies of headache leading to emergency room presentation in children. Despite this, few studies have investigated the treatment of acute migraine headache in the emergency room. We will perform a prospective, double-blind, placebo-controlled study of metoclopramide versus placebo in the treatment of acute migraine headache. The primary outcome will be the number of subjects headache free at two hours.
Inclusion criteria: inclusion criteria:

 Males or Females age 8-18 years

 Girls 11 years or older must have a negative urine/serum pregnancy test.

 Diagnosis of pediatric migrainous headache. The criteria for pediatric migraine headache based on the most recent ICHD criteria are listed below. The requirement of 5 attacks (A) will not be required for this study, this making the diagnosis migrainous headache. As described elsewhere in the protocol, this change is required to make the study applicable to ED patients who require treatment before five attacks have occurred.

Exclusion criteria: :

 Evidence that headache is due to a secondary underlying disorder based on history or physical examination.

 Pregnant or lactating females.

 Any investigational drug use within 30 days.

 Known to have a contraindication to metoclopramide or valproic acid such as pregnancy, liver disease, hematologic disease, or metabolic disease.

 Have used metoclopramide (or other antidopaminergic medications) or valproic acid within two days of presentation.

 Severe developmental disorders or mental retardation if insufficient information can be obtained to make a clear diagnosis of migraine or judge headache severity.

 If patients re-present to the ED, they can not be re-enrolled.


Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

Summary: Infants handle ketorolac differently than adults. Study of handling of this pain medication given to infants following surgery. Detailed analysis of how the drug is eliminated from age 2 months to 18 months. Compared morphine use in infants who received the drug to the group getting placebo. Safety testing for kidney and liver function, breathing measured by continuous oximetry, and any bleeding issues.
Inclusion criteria: inclusion criteria:

 Non-prematurely-born infants admitted to hospital following surgery ages 2-18 months, studied by age group 12-18 months, 6-12 months, < 6 months

Exclusion criteria: :

 Bleeding history in infant or family

 Coagulopathy

 Gastrointestinal bleeding history

 Renal or hepatic disease assessed by history and by pre-drug blood tests

 Premature birth (<36 weeks gestation)

['Ketorolac Tromethamine 1 mg/kg', 'Ketorolac Tromethamine 0.5 mg/kg', 'Placebo']

Ketorolac Tromethamine 1 mg/kg
Ketorolac Tromethamine 0.5 mg/kg
Placebo


Evaluation of Low Source of Signal in SCOUT DS

Summary: The overall objective of this study is to increase the number of dark skin tone individuals in the data set and evaluate if this increase in dark skin tone data has an impact on the accuracy of the SCOUT DS Diabetes Risk Score (DRS).
Inclusion criteria: inclusion criteria:

 Dark Skin Tone (Von Luschan chromatic skin color > 35)

 Age greater than or equal to 45 years;

 OR

 Age 18 to 44 years and a BMI > 25 kg/m² with one or more of the following diabetes risk factors:

 Habitually physically inactive (less than 30 minutes of moderate physical activity most, if not all, days of the week)

 Has a first-degree relative with type 2 diabetes

 African American, Latino, Native American, Asian American, Pacific Islander

 Has delivered a baby weighing > 9 lb or previously diagnosed with gestational diabetes

 Hypertension (≥140/≥ 90 mmHg) or being treated for hypertension

 HDL cholesterol level < 35 mg/dL and/or a fasting triglyceride level ≥ 250 mg/dL or being treated for dyslipidemia with medication

 Has been previously diagnosed with Polycystic Ovary Syndrome (PCOS)

 Had impaired glucose tolerance or impaired fasting glucose on previous testing within the last 3 years

 Conditions associated with insulin resistance such as severe obesity or acanthosis nigricans

 History of vascular disease including heart attack, stroke, angina, coronary heart disease, atherosclerosis, congestive heart failure or peripheral arterial disease

Exclusion criteria: :

 Prior participation under VeraLight protocols: VL-2710, VL-2711 or VL-2712

 Under 18 years of age

 Receiving investigational treatments in the past 14 days

 Psychosocial issues that interfere with an ability to follow study procedures

 Conditions that cause secondary diabetes including Cushing's syndrome, acromegaly, hemochromatosis, pancreatitis, or cystic fibrosis

 Diagnosed with any type of diabetes, including type 1 or 2

 Taking glucose lowering medications

 Known to be pregnant

 Receiving dialysis or having known renal compromise

 Scars, tattoos, rashes or other disruption/discoloration on the left volar forearm.

 Recent (within past month) or current oral steroid therapy or topical steroids applied to the left forearm; inhaled steroid therapy is not excluded

 Current chemotherapy, or chemotherapy within the past 12 months

 Receiving medications that fluoresce*

 Known to have, or at risk for, photosensitivity reactions ( e.g., sensitive to ultraviolet light, or taking medication known to cause photosensitivity)

 Known to have, or at risk for, sensitivity to skin lotions or shaving (creams, lotions, soap, shaving cream)

 Prior bariatric surgery

['Metabolic Syndrome', 'Impaired Glucose Tolerance', 'Gestational Diabetes']

Metabolic Syndrome
Impaired Glucose Tolerance
Gestational Diabetes


Comparison of Balloon Kyphoplasty and Vertebroplasty in Subacute Osteoporotic Vertebral Fractures

Summary: This study aims to compare two treatments in subacute (more than 6 week duration) non-traumatic (usually osteoporotic) vertebral fractures. The two treatments are the following:~Vertebroplasty consisting in the percutaneous injection into the fractured vertebra of polymethylmetacrylate cement (the cement used to fix prosthesis in joint replacement) through a posterior route through the vertebral pedicles under radiological guidance.~Balloon Kyphoplasty which consists of placing through a percutaneous posterior approach under radiological guidance, into the fractured vertebra a balloon which is inflated with fluid and creates a cavity. This may restore part of the vertebral height loss due to the fracture. In addition, after balloon deflation, polymethylmetacrylate cement is injected with low pressure into the created cavity to fix fracture reduction. The study will indicate if balloon kyphoplasty is able to restore vertebral height of the fractured vertebra better than vertebroplasty.
Inclusion criteria: inclusion criteria:

 Patient is able to undergo the vertebroplasty or Balloon kyphoplasty procedure

 Patient has read and sign the informed consent

 Male or female, 50 years or older

 One or two non-traumatic vertebral fracture(s):

 Of osteoporotic origin (low speed trauma such as fall from his own height or less than 80 cm)

 Fracture(s) older than 6 weeks duration after the onset of pain related to the fracture· The fracture(s) exhibit(s) high signal intensity on T2-weighted images and a benign appearance at MRI

 Persistent pain despite medical treatment according to VAS ≥ 5 or a last resort to morphine treatment

 The patient will be able to receive the selected protocol treatment within 15 days after treatment randomization.

 The benign nature of the vertebral fracture has to be confirmed by the results of the biopsy performed during vertebroplasty or balloon kyphoplasty.

Exclusion criteria: :

 Patient with a vertebral fracture of less than 6 week duration after onset of fracture-related symptoms.

 Neurological signs related to the vertebral fracture to treat

 History of surgical or percutaneous spine treatment except simple discectomy at a single or multiple vertebral levels with no residual pain.

 Patient with more than 2 fractures corresponding to the inclusion criteria (old fractures are not taken into account)

 Known allergy to a contrast media or to one of the cement components used for kyphoplasty.

 More than two recent vertebral fractures

 Current infection

 Impossibility to perform the percutaneous approach of the vertebra to treat.

 Known allergy to a contrast media or to one of the cement components used for kyphoplasty.

 Reduction by more than 50% of the anteroposterior width of the bony spinal canal due to the vertebral fracture to treat.

 Vertebral fracture with loss of 90%or more of the vertebral body height

 Malignant and traumatic vertebral fractures

 Contraindication to MRI :

 Metallic implant : pace-maker, no auditive implant , metallic vascular or movable cardiac device

 Metallic surgical clips Claustrophobia

 Evolutive cardiac disease nonreactive to medical treatment

 Patient presenting a non correctable spontaneous or therapeutic coagulation disorder.

 Presence of an unexplained biological inflammatory syndrome with VS≥20

 Non compliant patient: Impossibility to participate to the study and to be followed up for 1 year.

 Pregnant or breast feeding women

 Patient not affiliated to social security

['Osteoporotic Vertebral Fracture', 'Between T5 and L5', 'Chronic Arthritis, Longer Than Six Weeks Duration']

Osteoporotic Vertebral Fracture
Between T5 and L5
Chronic Arthritis
Longer Than Six Weeks Duration


Effects of Pain on Driving Performance and Cognition.

Summary: It has been suggested that cognitive functioning is impaired in chronic pain patients. Since most of these pain patients engage in daily activities including driving, it was hypothezised that they may have an increased risk of becoming involved in traffic accidents.
Inclusion criteria: inclusion criteria:

 age driving licence driving experience normal vision right-handed fluently Dutch speaking

Exclusion criteria: :

 psychological or physical disorder drug or alcohol abuse psychotropic medication use excessive smoking, drinking


A Safety and Efficacy Study of Hospitalized Patients With Community-Acquired Pneumonia and Sepsis

Summary: The objective of this study is to demonstrate the safety and efficacy of IC14 in the treatment of hospitalized patients with community-acquired pneumonia and sepsis.
Inclusion criteria: inclusion criteria:

 Current diagnosis of community-acquired pneumonia.

 Evidence of systemic inflammatory response to infection.

Exclusion criteria: :

 Atypical or viral pneumonia based on clinical or epidemiologic suspicion by the investigator.

 Presence of organ failure.

['Recombinant Chimeric Monoclonal Antibody']


A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma

Summary: Relapsed and/or refractory neuroblastoma, osteosarcoma, Ewing sarcoma and melanoma are considered difficult to treat and cure. For this study we are testing the use of a new experimental (investigational) antibody called hu14.18K322A. GD2 is expressed on the surface of most of these tumor types.~Two schedules of hu14.18K322A antibody will be evaluated in this study, (1) daily for four consecutive days schedule every 28 days and (2) once weekly for 4 weeks schedule every 28 days. Approximately 25-40 participants will be required to define the maximum tolerated dose for each schedule. Participants will continue on treatment for a maximum of 4 to 8 courses or until one or more of the criteria for off-treatment are met.
Inclusion criteria: inclusion criteria:

 Diagnosis:

 Part A: Recurrent or refractory neuroblastoma or melanoma.

 Part B: Recurrent or refractory neuroblastoma or melanoma.

 Part C: Recurrent or refractory osteosarcoma and Ewing sarcoma.

 Age: ≤ 21 years of age at the time of enrollment (i.e. participants are eligible until they reach their 22nd birthday).

 Does not have a clinically significant neurologic deficit or objective peripheral neuropathy (greater than or equal to grade 2). Peripheral (sensory or motor) neuropathy related to limb sparing procedure or amputation is allowed.

 Life expectancy: at least 8 weeks.

 Organ Function: Must have adequate organ and marrow function

 Performance status: Karnofsky ≥ 50 for > 10 years of age; Lansky ≥ 50 for children < 10 years of age.

 Prior Therapy: Patient must have fully recovered from the acute toxic effects of all prior therapy prior to enrolling on study.

 Myelosuppressive Chemotherapy: Must not have received myelosuppressive therapy within 2 weeks prior to study entry (4 weeks if nitrosurea).

 Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with biologic agent, including retinoic acid. Participants receiving IVIG are eligible; however, participant must not receive IVIG during the 4 days of antibody infusion.

 Radiation therapy: At least 2 weeks since prior local radiation therapy at the time of study entry.

 Growth factors: Must not have received hematopoietic growth factors (G-CSF, GM-CSF) for at least 1 week prior to study entry.

 Investigational agent: Must not have received investigational agent within 14 days of study entry.

 Immune therapy: Must not have received immunosuppressive (including glucocorticoids), immunostimulatory or any immunomodulatory treatment within 2 weeks of study entry. Steroid containing inhalers, steroid replacement for adrenal insufficiency and steroid premedication for prevention of transfusion or imaging contrast agent-related allergic reaction will be permitted.

 Patients may have had prior CNS metastasis providing: CNS disease has been previously treated and CNS disease has been clinically stable for 4 weeks prior to study entry (assessment must be made by CT or MRI).

 Written informed consent following institutional and federal guidelines.

Exclusion criteria: :

 Prior monoclonal antibody: Participants having received in vivo monoclonal antibodies for biologic therapy or for tumor imaging are eligible provided they did not experience a severe allergic reaction with the antibody.

 Pregnancy or Breast Feeding: Study participants who are pregnant are not eligible for this study. Pregnancy tests must be obtained in girls who are > 10 years of age or post-menarchal within 7 days prior to study enrollment. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during participation in the trial. Breast feeding should be discontinued if a mother wishes to participate in this study.

 Allergy: known hypersensitivity to other recombinant human antibodies.

 An uncontrolled infection.

['Neuroblastoma', 'Melanoma', 'Osteosarcoma', 'Ewing Sarcoma']

Neuroblastoma
Melanoma
Osteosarcoma
Ewing Sarcoma


Modafinil for Atypical Depression

Summary: The purposes of the study are to: 1) evaluate the short-term efficacy and safety of modafinil in atypical depression; and 2) to evaluate the efficacy of modafinil in preventing relapse of atypical depression. The hypothesis is that modafinil is safe and effective in the treatment of atypical depression.
Inclusion criteria: inclusion criteria:

 adults 18-65 years of age

 DSM-IV criteria for major depressive episode with atypical features as assessed by the Atypical Depression Diagnostic Scale

 minimum score of 18 on the Hamilton Depression Scale (29-item version) at baseline

 baseline Clinical Global Impressions Severity score of 4 or more

 written informed consent

 negative serum pregnancy test for women of childbearing potential

Exclusion criteria: :

 any current primary DSM-IV Axis I disorder other than depression

 history of DSM-IV diagnosis of bipolar I disorder, schizophrenia or other psychotic disorder, mental retardation or other pervasive developmental disorder, or cognitive disorder due to a general medical condition

 history of substance abuse or dependence within the last 3 months

 suicide risk or serious suicide attempt with the last year

 clinically significant medical condition or laboratory or EKG abnormality

 history of non-response to three prior adequate trials of antidepressants

 women of childbearing potential who are unwilling to practice an acceptable method of contraception

 history of hypersensitivity to modafinil

 use of an investigational medication within the last 28 days

 use of antidepressant medication with 28 days of screening


Pilot Study of Femring Estrogen Supplementation During Depo-Provera Initiation

Summary: Many women choose Depo-Provera for birth control because it is easy to use and very effective. However, a significant number of Depo-Provera users experience irregular bleeding during the first 90 days. Many users discontinue after their first injection due to irregular bleeding. This study will evaluate the effect of using an estrogen vaginal ring during the first 90 days of Depo-Provera use to see if it is acceptable to women and whether it decreases irregular bleeding during the first 90 days of use and increases continuation to a second injection.
Inclusion criteria: inclusion criteria:

 Women age 18 or older who are initiating Depo-Provera for contraception

 English or Spanish-speaking

 Have a negative urine pregnancy test

Exclusion criteria: :

 Contraindications to either Depo-Provera or Femring (estrogen vaginal ring)

 Have used Depo-Provera or Mirena in the prior 6 months

 Have had an induced abortion, spontaneous abortion, or birth in prior 8 weeks


Voice and Swallowing Outcomes Following Revision Anterior Cervical Spine Surgery

Summary: Evaluate voice and swallowing outcomes post operatively.
Inclusion criteria: inclusion criteria:

 Patients undergoing revision anterior cervical spine surgery

Exclusion criteria: :

 Primary pathology of the upper aero-digestive tract other than mild chronic pharyngitis, pre-existing vocal cord paralysis.


Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity in Patients With Obstructive Sleep Apnea - Study B

Summary: Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal participants. Until recently, the search for medicines to activate pharyngeal muscles in sleeping humans has been discouraging. However, exciting new animal research has shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle activity to waking levels. In this protocol the investigators will test the effect of desipramine (a tricyclic antidepressant with strong noradrenergic and antimuscarinic effects) on upper airway collapsibility and genioglossus muscle activity (EMG GG) during sleep in OSA patients.
Inclusion criteria: inclusion criteria:

 Diagnosed OSA (moderate-to-severe; apnea hypopnea index >15 events/hr)

Exclusion criteria: :

 Cardiovascular disease other than well controlled hypertension

 Depression


Thrombolysis Versus Primary Angioplasty for AMI in Elderly Patients

Summary: General objective: To compare the efficacy and safety of primary angioplasty(PA) with that of thrombolytic therapy (TT) for the treatment of AMI in patients >=75 years old with ST-segment elevation or LBBB AMI <6 hours of evolution without contraindications for TT.~Hypothesis: The therapeutical strategy based on PA is superior to that based initially on TT in patients >=75 years old with AMI.~Participating Centers: 27 Spanish hospitals performing >50 PA/year. Primary Endpoint (PE): Incidence of the aggregate of death of any cause, reinfarction or disabling stroke at 30 days. There are also 7 secondary endpoints (SE).~Procedure: Diagnosis of inclusion/exclusion criteria --> Centralized randomization --> Treatment allocation to 1) TT with weight adjusted TNK + unfractionated heparin or 2) PA within 120 minutes. Estimated Sample size and recruitment time: 570 patients in 19 months. Follow-up: Blinded evaluation of events (PROBE regulations) specified in PE and SE at 30 days and 12 months. Quality control: 100% variable and follow-up review by external CRO. Safety Committee and Event Adjudication Committee formed by experts not participating in the study.
Inclusion criteria: inclusion criteria:

 Subjects of 75 or more years of age

 Diagnosis of AMI: chest pain or any symptom of myocardial ischemia of, at least, 20 minutes of duration, not responding to nitrate therapy, an evolution period of less than 6 hours after symptom onset until randomization process, and, at least, one of the following alterations:

 ST-elevation >=2 mm in 2 or more precordial leads

 ST-elevation >=1 mm in 2 or more anterior leads

 Complete de novo (or probably de novo) left bundle branch block (LBBB)

 Subject should be able to give informed consent prior to randomization process and should agree to fulfill all procedures described in the protocol, including follow-up after hospital discharge. A written consent signed by a close relative with witness is also acceptable.

Exclusion criteria: :

 Documented contraindication to the use of fibrinolytics. 1.1. Internal active bleeding or known history of hemorrhagic diathesis 1.2. History of previous CVA of any kind or at any time 1.3. Intracranial tumor, arteriovenous malformation, aneurysm or cerebral aneurysm repair 1.4. Major surgery, parenchymal biopsy, ocular surgery or severe traumatism in the 6 weeks prior to randomization 1.5. Unexplained puncture in a non-compressible vascular location in the last 24 hours prior to randomization 1.6. Confirmed arterial hypertension with a reliable measurement of systolic AP >180 mmHg or diastolic AP >110 mmHg 1.7. Known thrombocytopenia < 100.000 platelets/mL 1.8. Prolonged (>20 minutes) or traumatic cardiopulmonar resuscitation (CPR) in the 2 weeks prior to randomization 1.9. History or signs suggesting aortic dissection

 Cardiogenic shock

 Estimated door-to-needle time >120 minutes

 Administration of fibrinolysis in the 14 days prior to randomization

 Administration of any glycoprotein IIa/IIIb inhibitor in the 24 hours prior to randomization

 Administration of any Low Molecular Weight Heparin (LMWH) in the 8 hours prior to randomization

 Actual oral anticoagulant treatment

 Suspected AMI secondary to occlusion of one lesion treated previously with a percutaneous coronary intervention (within the previous 30 days for angioplasty or conventional stent and within the previous 12 months for coated stents)

 Dementia or acute confusional state at the time of randomization

 Subject incapacity or unwillingness to give informed consent -at least, verbally

 Known renal failure (basal creatinine> 2,5 mg/dl)

 Reduced life expectancy (<12 months) due to advanced or terminal concomitant condition

 Subject participation in another clinical trial (assessing a drug or a device) in the 30 days prior to randomization

['Tenecteplase + UFH (+ clopidogrel, since 01/97)', 'Primary angioplasty']

Tenecteplase + UFH (+ clopidogrel
since 01/97)
Primary angioplasty


Calcium and Bone Mass in Young Females

Summary: We originally suggested that calcium in the diet is important in determining the amount of bone (bone mass) that builds up in young adults. We are testing the effect of calcium on bone mass in 354 Caucasian (white) girls. At the start of this 7-year study, the average age of the girls was 11 years, and they had not yet reached puberty. The study will also provide information about the effect of calcium on body composition (body fat) and blood pressure in young women.~We have been giving calcium to one group of participants in this study and giving a placebo (an inactive pill, or sugar pill) to the other group. The results of this research will be important in preventing osteoporosis, because building more bone as a young person should reduce a woman's chances of developing osteoporosis later in life.
Inclusion criteria: inclusion criteria:

 Pubertal stage II

 Calcium intake below a threshold level

 Caucasian

 Normal health

Exclusion criteria: :

 Medications affecting calcium and bone metabolism

 Chronic diseases

 Metabolic bone disease

 Abnormality in calcium metabolism


Dynamic Plantar Microvascular Skin Response to Compressive Loads in At-risk Diabetic and Healthy Control: a Pilot Study

Summary: The purpose of this pilot study is to compare the dynamic response of microcirculation in the skin on the bottom of the big toe after applying controlled plantar stress in 25 diabetic subjects with a history of foot ulcer and 25 age-matched healthy controls to better understand the role of local hypoxia in neuropathic foot ulceration in subjects with diabetes.~The investigators hypothesize that if they apply a gait simulating load to the plantar foot and measure microvascular function, diabetic individuals will demonstrate an increased delay in reestablishing microvascular flow compared to healthy individuals.
Inclusion criteria: inclusion criteria:

 between ages 40 and 75

 history of diabetic neuropathic plantar ulcer (test subjects)

 no history of diabetes (control subjects)

 no peripheral sensory neuropathy (control subjects)

Exclusion criteria: :

 amputation or surgery on right Great Toe


Clinical Study to Evaluate Efficacy and Safety of ALLO-ASC-DFU in Patients With Diabetic Foot Ulcers

Summary: This is a phase II single-blinded study to evaluate the efficacy and safety of ALLO-ASC-DFU in patients with Diabetic Foot Ulcer, compared to standard therapy.
Inclusion criteria: inclusion criteria:

 Subject is between 18 years and 80 years of age.

 Subject is diagnosed with Type I or Type II diabetes, and had defined as diabetic foot ulcers presence of wound for more than 4 weeks at the screening visit.

 Ulcer located the foot, and ulcer size is between 1 cm^2 and 25 cm^2.

 Ulcer extends into the dermis, subcutaneous tissue, tendon or joint capsule (Wagner grade 1 or 2).

 Ulcer is free of necrotic debris.

 Subjects had adequate circulation to ulcer as documented by one of the methods below:

 Palpation of pulses around ulcer using Doppler exam

 Ankle Brachial index (ABI) values ranging between 0.7 and 1.3, or

 Transcutaneous Oxygen Pressure (TcPO2) > 30 mmHg.

 Subject is able to give written informed consent prior to study start and to comply with the study requirements.

Exclusion criteria: :

 Ulcer is of non-diabetic pathophysiology.

 The ulcer has increased or decreased in size by 30% or more during one week after the screening visit.

 Subject is Human Immunodeficiency Virus (HIV) positive.

 Subjects with severe hepatic deficiencies.

 Subjects with a glycated hemoglobin A1c (HbA1c) level of > 15%.

 Subject who are allergic or have a hypersensitive reaction to bovine-derived proteins or fibrin glue.

 Subjects requiring intravenous (IV) antibiotics to treat the index wound infection.

 Subjects with severe renal deficiencies that is uncontrolled by dialysis

 Subjects who are pregnant or breast-feeding.

 Subjects who are unwilling to use an effective method of contraception during the study.

 Current evidence of severe infection including pus drainage from the wound site.

 Subjects who have a clinically relevant history of alcohol or drugs abuse.

 Subject's blood sugar is > 450 mg/dL at postprandial.

 Subjects who are not able to understand the objective of this study or to comply with the study requirements.

 Subjects who are considered to have a significant disease which can impact the study by the investigator.

 Subjects who are considered not suitable for the study by the investigator.

 Subjects who have a history of surgery for malignant tumor within the last five years (except carcinoma in situ).

 Subjects who are currently or were enrolled in another clinical study within 60 days of screening.

 Subjects who have undergone wound treatments with cell therapy, dermal substitutes, or other biological therapies within the last 30 days.

 Subjects who are receiving oral or parenteral corticosteroids, immunosuppressive, or cytotoxic agents to unstable dosage.


Effect Of Treatment With Oral Zolpidem On Polysomnography And Actigraphy Measures In Healthy Volunteers

Summary: This study will assess the feasibility of conducting sleep studies in a clinical research unit environment. In addition, the sensitivity of polysomnography and mobile actigraphy technologies will be compared for evaluating sleep stages and sleep architecture.
Inclusion criteria: inclusion criteria:

 Age 18-55

 BMI 18-30 kg/m2

 body weight > 50 kg

Exclusion criteria: :

 no history of sleep disorder

 no concurrent medications

 no alcohol use

 no medical issues

 no smoking


Bacterial Meningitis in Adults: Analysis of the Determinants of Mortality and Neurosensory Sequelae

Summary: Major changes in the epidemiological characteristics of bacterial meningitis have been observed as a result of changes in behaviour, human interventions (use of antibiotics, prophylactic vaccinations), as well as poorly elucidated mechanisms responsible for epidemic outbreaks.~The objective of this study is to identify the determinants of in-hospital mortality of bacterial meningitis in adults.~Hypothesis : the standardized data collection concerning cases of bacterial meningitis in adults with telephone follow-up would allow analysis of the determinants of mortality and neurosensory sequelae, description of the psychosocial impact and proposal of new treatment strategies.
Inclusion criteria: inclusion criteria:

 Positive CSF culture and/or positive soluble antigens in CSF with or without a cell reaction

 Positive PCR in CSF

 Purpura fulminant (with or without positive CSF culture)

 Positive PCR in blood and/or positive blood culture AND CSF cell reaction.

Exclusion criteria: :

 Age less than 18 years old

 Refusal to participate


PREVAIL: PREvention of VTE After Acute Ischemic Stroke With LMWH Enoxaparin ( - VTE: Venous Thromboembolism - LMWH: Low Molecular Weight Heparin)

Summary: Primary objective:~To demonstrate superiority of enoxaparin 40 mg sc qd in the prevention of VTE compared to UFH (unfractionated heparin) 5000 U sc q12 hours given for 10 ± 4 days following acute ischemic stroke.~Secondary objectives:~To compare the incidence of VTE between the 2 treatment groups at 30, 60, and 90 days from the time of randomization~To compare neurologic outcomes between the 2 treatment groups, including incidence of stroke recurrence, rate of stroke progression, and patient functional status, during the 10 ± 4 days of treatment, and after 30, 60, and 90 days from the time of randomization~To evaluate the safety of using enoxaparin compared to UFH for VTE prevention in patients following acute ischemic stroke
Inclusion criteria: inclusion criteria:

 Acute ischemic stroke, any territory, with an appropriate neuroradiologic study (head CT scan or brain MRI scan) providing results consistent with non hemorrhagic stroke

 Onset of symptoms of qualifying stroke within 48 hours prior to randomization. In patients receiving thrombolytic therapy for the acute stroke, such as tissue-type plasminogen activator (tPA), administration of study drug may not start until at least 24 hours after completion of thrombolytic therapy

 Significant motor impairment of the leg, as indicated by a NIHSS score ≥2 on item 6

 Inability to walk without assistance

Exclusion criteria: :

 Females who are pregnant, breast-feeding, or of childbearing potential and not using medically acceptable and effective contraception

 Clinical evidence of VTE at screening

 Any evidence of active bleeding on the basis of clinical judgment

 Prior history of intracranial hemorrhage (including that at screening)

 Spinal or epidural analgesia or lumbar puncture within the preceding 24 hours

 Thrombolytic therapy (e.g., tPA) or intra-arterial thrombolytic therapy within the preceding 24 hours.Thrombolytic therapy is permitted for treatment of the acute stroke but must have been completed 24 hours prior to randomization.

 Comatose at screening (NIHSS score ≥2 on item 1a)

 Known or suspected cerebral aneurysm or arteriovenous malformation

 Confirmed malignancy that may pose an increased risk for bleeding or otherwise compromise follow-up or outcome assessment (e.g., lung cancer)

 Impaired hemostasis, i.e., known or suspected coagulopathy (acquired or inherited); baseline platelet count <100,000/mm3; aPTT 1.5 X the laboratory upper limit of normal; or international normalized ratio(INR) >1.5

 Major surgery or recent major trauma within the previous 3 months

 Anticipated need for full-dose treatment with therapeutic levels of an anticoagulant (LMWH, UFH, oral anticoagulant), e.g., for cardiogenic source of embolism or dissection

 Treatment with a LMWH or UFH at prophylactic dose for more than 48 hours prior to randomization(patients receiving LMWH or UFH less than 48 hours prior to randomization may be randomized)

 Allergy to heparin or enoxaparin sodium, or known hypersensitivity to heparin, enoxaparin, or pork products

 History of heparin or enoxaparin induced thrombocytopenia and/or thrombosis (heparin-induced thrombocytopenia [HIT], heparin-associated thrombocytopenia [HAT], or heparin-induced thrombotic thrombocytopenia syndrome [HITTS])

 History of hypersensitivity to iodinated contrast media and/or iodine

 Bacterial endocarditis

 Prosthetic heart valve

 Known or suspected severe anemia (Hg <10.0 g/dL)

 Uncontrolled arterial hypertension (systolic blood pressure [BP] >180 mmHg or diastolic BP >100 mmHg) at the time of randomization or clinical hypertensive urgency

 Any other clinically relevant serious diseases, including severe liver disease or renal failure [creatinine clearance <30 mL/min on at least two occasions].

 Treatment with other investigational agents or devices within the previous 30 days, planned use of other investigational drugs or devices, or previous enrollment in this study.


Fibrin Sealant for the Sealing of Dura Sutures

Summary: The purpose of this study is to investigate the efficacy and safety of FS VH S/D 500 s-apr, a double virus-inactivated biological two-component fibrin sealant, for use in posterior fossa surgery as an adjunct to dura and dura substitute sutures in preventing postoperative cerebrospinal fluid (CSF) leakage.
Inclusion criteria: inclusion criteria:

 Preoperative inclusion criteria:

 Subjects undergoing elective craniotomy / craniectomy for pathological processes in the posterior fossa (such as benign and malignant tumors, vascular malformations, and Chiari 1 malformations) that result in dura defects requiring dura substitution for closure and who are able and willing to comply with the procedures required by the protocol

 Signed and dated written informed consent from the subject or from his/her legal representative prior to any study-related procedures

 Age >= 3 years, either gender

 Intraoperative inclusion criteria:

 Surgical Wound Classification Class I and Risk Index Category (RIC) <= 2. Penetration of mastoid air cells during partial mastoidectomy is permitted and will be recorded.

 A patch of autologous fascia or pericranium or suturable collagen-based dura substitute was cut to size and then sutured into the dura defect.

 The hem of native dura exposed along and under the craniotomy edge is wide enough to facilitate suturing and to allow for sufficient surface area for adherence of the investigational product.

Exclusion criteria: :

 Preoperative

['Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr)', 'Standard of care']

['Pathological Processes in the Posterior Fossa', 'Dura Defects']


Phenotype Depression Study

Summary: To facilitate the development of a personalized approach to the treatment of patients with major depression, this study is designed to elaborate the clinical and neurobiological phenotype of depressed patients with increased inflammation. The data obtained in this proposal will allow the investigators to test the hypothesis that depression and inflammation interact to elaborate a relatively discreet phenotype that warrants an individualized approach to diagnosis and treatment of patients with depression. Moreover, the identification of specific environmental risk factors for inflammation will foster the elaboration of preventative strategies for patients at risk.
Inclusion criteria: inclusion criteria:

 age 21-65 years including males, females and minorities

 diagnosis of DSM-IV major depression or Bipolar I or II with current episode of depression

 HDRS-17 > 20 and HDRS-24 > 24

 negative pregnancy test for women of childbearing potential

 not breast feeding

 stable on current dose of psychotropic medication or free from all psychotropic medications for 4 weeks prior to EUH CIN admission (8 weeks for fluoxetine)

 no suicide attempt within six months of screening

Exclusion criteria: :

 evidence of untreated or poorly controlled endocrine, cardiovascular, pulmonary, hematological, renal, or neurological disease

 history of CNS trauma or active seizure disorder requiring medication unless otherwise approved by principle investigator

 autoimmune or inflammatory disorder of any kind

 chronic infection (e.g. hepatitis B or C or HIV)

 chronic use of agents known to affect the immune system including glucocorticoid therapy within the past 1 year, methotrexate within the past 1 year, chemotherapy of any kind (past or present), immunotherapy of any kind (past or present), aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) (within the past 2 weeks) and statins (within the past 1 month) unless otherwise approved by principle investigator

 hemoglobinopathies (e.g. thalassemia)

 a positive pregnancy test

 organ transplants

 cancer of any type

 a score of <28 on the Mini Mental Status Exam (MMSE)unless otherwise approved by principle investigator

 meets criteria for schizophrenia (Given overlap of generalized anxiety disorder (GAD) with major depression, GAD will not be exclusionary)

 current eating disorders

 active abuse of alcohol or illicit/prescription drugs within the past year unless otherwise approved by principle investigator.

 MGH-S >3 unless otherwise approved by principle investigator

 BMI >40 unless otherwise approved by the principle investigator

 active suicidal intent or plan and a score >2 on the HDRS suicide item (item #3).

 any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with participating in or completing the protocol


Pexacerfont for Stress-induced Food Craving

Summary: Background:~- Stress can cause people to give in to temptations to eat less healthily. People who are on weight loss diets often have problems sticking to their diets when they are stressed. Some tests have shown that the drug pexacerfont can help reduce stress-related seeking of high-calorie foods. However, it has not been tested on reducing food craving. Researchers want to test pexacerfont on people who are on diets to see if it can reduce stress-related food cravings.~Objectives:~- To see if pexacerfont can help reduce stress-induced food cravings.~Eligibility:~- Individuals between 21 and 65 years of age who are on a diet to control their weight.~Design:~Participants will be screened with a physical exam and medical history. This study requires seven visits over about 35 days.~Participants will take either pexacerfont or placebo pills during the study. They will have three pills every morning. They will record video of themselves taking the pills every day.~Every evening, participants will fill out a questionnaire. It will ask questions about feelings and behaviors related to eating and food craving.~Participants will have regular study visits while taking the pills. The visits will involve questions about stressful situations and food cravings. One visit will involve a mildly stressful math test, followed by tasting of different foods. This test will look at whether pexacerfont can affect food preferences. Participants will provide blood and saliva samples as directed at these study visits.~Participants will have follow-up phone calls 1, 3, and 6 months after the end of the study.
Inclusion criteria: inclusion criteria:

 Body Mass Index (BMI) > 22 kg/m(2)

 Score of 15 or higher on the Dietary Restraint Scale, with endorsement of the Restraint

 Scale item Do you give too much time and thought to food?

 Age 21 - 65 years.

 (4a) For women of childbearing potential: must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study drug, and agree to use an adequate method of contraception to avoid pregnancy for a period of 6 months beginning from first dose of randomized treatment. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Adequate methods of contraception for sexually active women are having a male sexual partner(s) who is surgically sterilized prior to inclusion; having a sexual partner(s) who is/are exclusively female; using oral contraceptives (either combined or progesterone only) with a single-barrier method of contraception consisting of spermicide and condom or diaphragm; using double-barrier contraception, specifically, a condom plus spermicide and a female diaphragm or cervical cap; or using an approved intrauterine device (IUD) with established efficacy.

 (4b) Men, unless surgically sterilized (vasectomy with documentation of azoospermia), must agree to practice abstinence or use barrier contraception, and not donate sperm, for a period of 6 months beginning from first dose of randomized treatment.

Exclusion criteria: :

 Current employment at NIDA IRP or Bristol-Myers Squibb (BMS), or being in the immediate family of an employee. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

 Current participation in another clinical study that includes exposure to an investigational or non-investigational drug or device.

 Participation in a clinical study for a condition related to weight or dieting within the preceding month.

 Any history of participation in a trial involving pexacerfont or closely related compounds.

 Any medical condition or laboratory finding that, in the judgment of the investigators, could adversely affect safety or study integrity. Examples include but are not limited to diabetes type 1 and type 2, ischemic heart disease, uncontrolled hypertension, and history of cerebrovascular accident or transient ischemic attack.

 For women: pregnancy, breastfeeding, or planning to become pregnant within 6 months from the administration of first dose of study drug.

 Past or present diagnosis of any eating disorder, including Anorexia Nervosa, Bulimia Nervosa, and Eating Disorder NOS (e.g., Binge-Eating Disorder). (Eating-disordered individuals probably represent a distinct population and should therefore be studied separately.)

 Past or present diagnosis of schizophrenia, bipolar disease, or any psychotic disorder; past or present diagnosis of dementia or any other disorder that has led to a clinically significant cognitive impairment; present diagnosis of any mood or anxiety disorder; any other psychiatric condition that presently requires, or in the past month has required, pharmacological intervention.

 Past or present diagnosis of any substance-use disorder except nicotine dependence.

 Urine tests positive for illegal drugs.

 Evidence of thyroid disorder by medical history or screening physical exam, with TSH < 0.36 or greater than 3.74 UIU/ml; or current or history of use of thyroid medication.

 Adrenal or pituitary pathology as evidenced by medical history or suggested by abnormal screening labs.

 Current seizure disorder or a significant history (as judged by the investigators) of a seizure disorder, other significant neurological disorders (e.g., Parkinson's Disease, multiple sclerosis, stroke, neurodegenerative disease, cerebral palsy) or severe head trauma (including closed head trauma, penetrating head injury, skull fracture, or intracranial hemorrhage), or CNS tumor.

 Active liver disease or a history of hepatic intolerance to medications that, in the investigators' judgment, is medically significant.

 History of diabetes mellitus type I and II or gastric bypass or reduction surgery.

 Justification: illnesses that change metabolism or the absorption from the GI tract, would interfere with drug metabolism or absorption).

 Difficulty swallowing tablets or capsules.

 Exclusionary physical and laboratory test findings:

 QTc > 475 msec

 platelets less than or equal to 75,000/mm(3)

 hemoglobin less than or equal to 9g/dL

 neutrophils, absolute less than or equal to 1000/mm3

 SGOT (AST) > 2.5 times upper limit of normal

 SGPT (ALT) > 2.5 times upper limit of normal

 bilirubin 2 times upper limit of normal

 GFR < 60mL/min/1.73m2 or significant proteinuria

 diastolic blood pressure > 105 mmHg

 TSH < 0.36 or > 3.74 UIU/ml

 Current use or history of use in the last 3 months of psychiatric medications, including but not limited to antidepressants, lithium, antipsychotics, anxiolytics, antiepileptics, opiates, or hypnotics.

 Any change in a non-excluded medication in the past 3 months.

 Systemic intake of corticosteroids acutely within 2 weeks or chronically (> 28 days) within the last 6 months. (Topical hydrocortisone and inhaled corticosteroids are allowed.)

 Use of medications that are CYP3A4 inhibitors or inducers (see Appendix 3); study applicants should not take these medications for at least 7 days prior to randomization and during the remainder of the study.

 Dietary restrictions or food aversions that would interfere with valid assessment of eating in our laboratory sessions.

['Daily Oral Pexacerfont for 28 Days (300 mg/Day Loading Dose for 7 Days, Followed', 'Placebo']


Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension

Summary: The purpose of this study is to compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone, once daily (QD), versus olmesartan medoxomil-hydrochlorothiazide in adults with essential hypertension.
Inclusion criteria: inclusion criteria:

 Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg on Day, or has not received antihypertensive treatment within 14 days prior to Screening and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day 1.

 Females of childbearing potential who are sexually active agree to routinely use adequate contraception, and can neither be pregnant nor lactating from before study participation to Screening to 30 days after the last study drug dose.

 Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.

 Is willing to discontinue current antihypertensive medications up to 3 weeks before enrollment.

Exclusion criteria: :

 Has a mean clinic diastolic blood pressure (sitting, trough) greater than 119 mm Hg on Day 1.

 Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).

 Has a recent history (within the last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident or transient ischemic attack.

 Has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome).

 Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.

 Has severe renal dysfunction or disease.

 Has known or suspected unilateral or bilateral renal artery stenosis.

 Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.

 Has poorly-controlled type 1 or 2 diabetes mellitus at Screening.

 Has hypokalemia or hyperkalemia at Screening.

 Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.

 Has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow according to the protocol.

 Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.

 Has been randomized/enrolled in a previous azilsartan or azilsartan medoxomil plus chlorthalidone study.

 Currently is participating in another investigational study or has received any investigational compound within 30 days prior to Screening.

 Has a history of drug abuse or a history of alcohol abuse within the past 2 years.

 Is taking or expected to take any excluded medication, including:

 Antihypertensive medications must be discontinued completely by Day -14, except antihypertensive medications used in the open-label treatment period in accordance with the titration-to-target blood pressure titration.

 Angiotensin II receptor blockers or thiazide-type diuretics other than study medication.

 Over-the-counter products not permitted by investigator.

['Azilsartan medoxomil and chlorthalidone', 'Olmesartan medoxomil and hydrochlorothiazide']


Pregabalin and Colonic Function

Summary: This study is being done to evaluate the effects of pregabalin, a drug approved for anticonvulsive therapy and for neuropathic pain, on colonic and sensory functions in healthy individuals.~The specific study hypotheses were as follows: 1) pregabalin increases sensation thresholds, decreases sensation ratings, and increases compliance in response to balloon distension in the colon; 2) pregabalin reduces colonic phasic and tonic motility in response to a standardized meal; and 3) sensation ratings are lower with higher colonic compliance.
Inclusion criteria: inclusion criteria:

 - Healthy males or females

Exclusion criteria: :

 Abdominal surgery other than appendectomy, laparoscopic cholecystectomy, cesarean section, vaginal or laparoscopic hysterectomy or tubal ligation

 A history of chronic gastrointestinal or systemic illnesses that could affect gastrointestinal motility

 Any history of hypertension

 Use of medications that may alter gastrointestinal motility or interact with the study medications

 Use of any of the study medications within the past 30 days

 Pregnancy

 Chronic renal insufficiency (serum creatinine >1.5 mg/dL)

 Psychiatric or psychologic dysfunction.

['Pregabalin', 'Placebo', 'Bowel preparation']


Cognitive Training for the Remediation of Functional Brain Health in HIV

Summary: Cognitive deficits in HIV reflect degraded brain network functioning that may be amenable to remediation through cognitive training. In this sub-study, we will make use of Plasticity-based Adaptive Cognitive Remediation (PACR), which applies well-understood techniques derived from brain plasticity and implicit/procedural/perceptual learning to improve the speed and accuracy of information processing, with exercises that are designed to drive generalized improvements. Simultaneously, these exercises heavily engage neuromodulatory systems to re-establish their normal control over learning and memory. As an individual restores these degraded abilities through intensive procedural learning, the encoding of naturalistic information significantly improves, and all resulting declarative memory and cognitive functions based on the quality of that incoming information necessarily improve as well, leading to improvement that generalizes beyond the trained tasks.~A subset of 80 HIV+ individuals will undergo eight weeks of PACR to determine its feasibility and appropriateness for people with mild cognitive difficulties related to HIV infection. The results of this study are expected to be pivotal in generating data to create an optimal training program aimed at stabilizing or improving brain function in HIV infected individuals experiencing cognitive decline.
Inclusion criteria: inclusion criteria:

 age 35 years or older;

 HIV infection for at least 1 year;

 able to communicate in English or French;

 capable of providing informed consent;

 easy access to the internet;

 EEG and MRI compatible

Exclusion criteria: :

 presence of dementia;

 life expectancy < 3 y;

 other neurological disorder including active opportunistic CNS infection;

 psychotic disorder;

 current substance dependence or abuse; and

 Hepatitis C requiring interferon therapy during the study period

['Plasticity-based Adaptive Cognitive Remediation (PACR)']

['HIV - Human Immunodeficiency Virus', 'Cognitive Impairment']

HIV - Human Immunodeficiency Virus
Cognitive Impairment


Study of Incidence of Drug-induced Upper Gastrointestinal Bleeding

Summary: The purpose of this study is to determine and analyse the incidence, severity, risk factors and routine management of acute drug-induced upper gastrointestinal bleeding (UGIB) in the population of Russian patients
Inclusion criteria: inclusion criteria:

 Established diagnosis of acute upper gastrointestinal bleeding, confirmed by presence of hematemesis/ coffee ground vomiting, melena, as well as other clinical or laboratory evidence of acute blood loss from the upper gastrointestinal tract

 Written informed consent provided prior the start of participation in the study.

Exclusion criteria: :

 Subjects who are unwilling or unable to provide informed consent.


Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer.

Summary: Atrophic vaginitis is a condition in which the skin lining of the vagina and labia becomes thin and symptoms develop including vaginal itching, vaginal discomfort and dyspareunia. These can significantly affect women's comfort, sexuality and quality of life.~Treatment for this condition includes estrogen given in pill form, commonly known as hormone replacement therapy and local estrogen treatments, such as vaginal estrogen creams and topical vaginal lubricants. Unfortunately, systemic estrogen is contraindicated in many women with breast cancer. Some providers also feel that women who are taking aromatase inhibitors for their breast cancer should also not use local estrogens as several small studies suggest that these treatments might effect estrogen levels and thus might change how effective the aromatase inhibitors are. If these women choose not to use any form of estrogen therapy there symptoms may not be well controlled with other treatments.~The investigators hypothesize that a vaginal testosterone cream might be a safe and effective alternative treatment for these women. This small study is intended to test the hypothesis that testosterone cream will not increase estrogen (estradiol) levels and that it will improve the symptoms of atrophic vaginitis including vaginal dryness, vaginal itching and pain with intercourse.~The investigators will enroll women in the trial who are taking an aromatase inhibitor and have the symptoms mentioned above. They will receive a testosterone cream which will be applied vaginally once a day for 28 days. If good results are found with a prespecified dose of testosterone, a lower dose will be tested in the next group of women enrolled.
Inclusion criteria: inclusion criteria:

 Histologically or cytologically confirmed breast cancer (any stage).

 Currently be using an aromatase inhibitor (anastrazole, exemestane or letrozole) for primary or adjuvant breast cancer treatment.

 Must have complaints of vaginal itching, vaginal dryness and/or dyspareunia.

 Not undergoing active chemotherapeutic or radiotherapeutic treatment

 Age >18 years

 Life expectancy of greater than 2 months.

 CALGB (ZUBROD) performance status <3.

 Post-menopausal - defined by absence of menses for at least 12 months and/or an FSH >25. Not post-menopausal as a function of medications intended to suppress ovarian function, such as gonadotropin releasing hormone agonists. Surgically post-menopausal subject eligible.

 The effects of topical testosterone cream on the developing human fetus at the recommended therapeutic dose are unknown. For this study only post-menopausal women are included and all women of child-bearing potential are excluded. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion criteria: :

 Patients who have not recovered from adverse events due to chemotherapeutic agents administered more than 4 weeks earlier.

 History of allergic reactions attributed to compounds of similar chemical or biologic composition to testosterone or the emollient delivery cream used in the study.

 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

 Pregnant women and women who are breast-feeding are excluded from this study because it is limited to post-menopausal women.

['Vaginitis', 'Dyspareunia', 'Breast Neoplasms']


Inhaler Lung Deposition in Chronic Obstructive Pulmonary Disease (COPD)

Summary: Patients with chronic obstructive pulmonary disease (COPD) experience breathing difficulties because the airways deep in their lungs become narrowed. COPD patients use inhaler drugs to provide relief from breathlessness. However, current inhalers are inefficient as they deliver a 'coarse-mist' of drug-droplets that do not reach the deep airways.~In our study, we will use an inhaler of 'fine-mist' drug-droplets, tagged with a radioactive tracer to track them. We will take images of the lungs to see if the fine-mist droplets reach the deep airways, and assess if this improves the breathing capacity in our patients. Our research may allow the development of new, more efficient inhalers to improve treatment for patients with COPD.
Inclusion criteria: inclusion criteria:

 - COPD patients, either male or female, over the age of 40 with a clinical diagnosis of COPD with airflow obstruction(FEV1/FVC<0.7) and post-bronchodilator FEV1>50% predicted, gas trapping (on lung volume testing), and decreased carbon monoxide transfer factor.

 Healthy subjects will be nonsmokers(or exsmokers stopped 5 years ago), will have no respiratory disease, normal spirometry and be age-matched to the COPD patients.

 Asthmatic subjects, either male or female, over the age of 18 with a clinical diagnosis of Asthma with airflow obstruction (FEV1/FVC<0.7).

 All patients should be capable of giving informed consent.

Exclusion criteria: :

 Oral corticosteroids taken within last month.

 Current involvement (or involvement in the last 4 weeks)in clinical trials assessing investigational medicinal products.

 Previous adverse reaction to short or long acting β2 agonist.

 Any subject with a contraindication to taking inhaled beta2-adrenoceptor agonists (especially salbutamol) as listed in the British National Formulary will not be entered into this study.

 Those who have experienced an acute respiratory exacerbation requiring emergency room treatment and/ or hospitalisation within four weeks of visit 1 (screening visit).

 Pregnant or breastfeeding women.

 Subjects unable to give Informed Consent.

['CHRONIC OBSTRUCTIVE PULMONARY DISEASE', 'ASTHMA', 'HEALTHY SUBJECTS']

CHRONIC OBSTRUCTIVE PULMONARY DISEASE
ASTHMA
HEALTHY SUBJECTS


Peripheral Nerve Block Anaesthesia for Ankle Fracture Surgery - an Exploratory Study: Is Rebound Pain a Problem?

Summary: The purpose of this exploratory study is to characterize the postoperative pain profile of patients undergoing operation with internal fixation of an ankle fracture under nerve block anaesthesia. Special attention is payed towards the possible existence and clinical relevance of a rebound pain phenomenon upon cessation of the nerve block.~Results are used to guide the set up of a randomized controlled trial on the subject.
Inclusion criteria: inclusion criteria:

 Patients >= 18 years old scheduled for internal fixation of an ankle fracture as defined above.

 Ability to read and understand Danish and give informed oral and written consent

Exclusion criteria: :

 Multitrauma patients / other simultaneous fractures

 Cognitive or psychiatric dysfunction causing expected inability to comply with study protocol

 CAVE nonsteroidal antiinflammatory drugs (NSAID) or Morphine or Local Anaesthetics as evaluated by anesthesiologist for any reason

 Primary investigator unavailable for PNB administration at scheduled time of operation

 Infection at PNB injection site

 Time from fracture to operation > 5 days

 Existing neuropathy with functional impairment of the fractured extremity

 Bodyweight < 50 kg

 Daily use of opioids > 2 weeks preoperatively

 Pregnancy

 Nephropathy requiring dialysis


Trial Of Normal Saline Versus Ringer's Lactate In Paediatric Trauma Patients

Summary: Background: Trauma is a major cause of death in children and teenagers. When young patients have suffered major traumatic injuries, they require intravenous (iv) fluids to keep their blood vessels full and ensure blood flow to vital organs. Current fluid guidelines by International Trauma Committees recommend either Normal Saline (NS) or Ringer's Lactate (RL) as the fluid of choice for these patients. Although these solutions share some similarities in their composition, there are also some significant differences in sodium, chloride and lactate concentrations. Despite these differences in fluid composition, there has never been a study comparing these two fluids in paediatric trauma patients to determine which is optimal. In this study, the investigators aim to determine the optimal fluid choice for trauma resuscitation of young patients.~Hypothesis: The investigators hypothesize that severely injured paediatric trauma patients resuscitated with NS will have optimal blood sodium levels compared to patients resuscitated with RL.~Methods: The investigators will study 50 paediatric trauma patients that will be randomized so that half will randomly receive NS and half will receive RL as their only iv fluid for 24 hours. After 24 hours, the investigators will compare in blood the sodium level, the amount of acid, and the concentrations of inflammation molecules in relation to those whom received NS versus RL.~Expected Results and Significance: Maintaining optimal levels of these biochemical markers is imperative in reducing morbidity and mortality in severely injured paediatric patients. If significant differences are present, the investigators will be able to determine which fluid is preferred and expect these data to complement current trauma resuscitation guidelines.
Inclusion criteria: inclusion criteria:

 Pediatric trauma patients with Injury Severity Score greater than 12

 Age 1-17 years

 Trauma within 8 hours

Exclusion criteria: :

 Injury Severity Score less than 12

 Pre-existing renal disease

 On medication that affects serum sodium (i.e diuretic therapy)

 Blood transfusion within first 24 hours

 Operation within first 24 hours

 Oral intake of fluid or solids in first 24 hours


Lung Ultrasound in the Evaluation of Pneumothorax Size

Summary: Background~Assessment of the percentage of lung collapse is crucial in the therapeutic decision-making of pneumothorax.~The methods normally used to this purpose are radiological. Computerized tomography scan (CT) is highly accurate because it allows the exact evaluation of the volume of the air layer. However, in clinical practice assessment of the volume of pneumothorax mainly relies on the measurement of the inter-pleural distance at conventional chest radiography (CXR). This latter method is inaccurate.~Lung ultrasound is a new method highly accurate in the first diagnosis of pneumothorax, with a sensitivity superior to CXR and similar to CT in case of traumatic pneumothorax.~The scientific community is actually debating about the usefulness of lung ultrasound in the quantification of pneumothorax []. Lung ultrasound can assess the superficial extension of the pneumothorax, but cannot evaluate its volume.~Aim~Main purpose of the study is to compare measurement of the superficial extension of pneumothorax on the chest wall obtained by lung ultrasound, to the evaluation of the air volume performed by CT in patients with pneumothorax.~The main hypothesis of the study is that the cut-off between small (<11% of lung collapse) and large (>11% of lung collapse) pneumothorax can be identified by a lung ultrasound evaluation of the superficial extension of pneumothorax.~Second purpose of the study is to compare the accuracies of lung ultrasound and CXR in predicting the volume of pneumothorax assessed by CT.~Secondary hypothesis is that lung ultrasound demonstrates greater accuracy in the prediction of volume of pneumothorax and percentage of lung collapse.~Methods~Patients with a diagnosis of pneumothorax confirmed at CT are prospectively enrolled and submitted to lung ultrasound within 20 min from the CT study.~Different locations of the sonographic lung point on the chest wall (i.e. the point on the chest wall where the sonographic pattern of the normally aerated lung alternates with the pathologic sonographic pattern of pneumothorax) are compared with different volumes of pneumothorax measured by CT.
Inclusion criteria: inclusion criteria:

 Radiologic diagnosis of pneumothorax

 Clinical need to perform a CT scan

 Ability to perform the lung ultrasound imaging within 20 minutes from the CT study

Exclusion criteria: :

 age less than 16 years


Feasibility Study Using Imaging Biomarkers in Lung Cancer

Summary: The purpose of this research study is to develop a method of using magnetic resonance imaging (MRI) to evaluate solitary pulmonary nodules (mass in the lung smaller than 3 centimeters). A pulmonary nodule is a mass or growth on the lung. An MRI is a scanning device that uses magnets to make images (pictures) of the body. This study is being done to determine what series of reactions (metabolic pathways) pulmonary nodules use as they burn sugar as fuel for growth. The manner in which the tumor burns (metabolizes) sugar for fuel is being investigated by using a natural, slightly modified, sugar solution (13C-glucose) and studying a small sample of the tumor once it is removed at the time of surgery.
Inclusion criteria: inclusion criteria:

 Subjects of all races and ethnic origins over 18 years of age will be recruited.

 Patients must have suspicious or known to be malignant solitary pulmonary nodule,5cm or less in size.

Exclusion criteria: :

 Patients with a contraindication to MRI examinations will be excluded from this study.

 Contraindications to MRI examinations include:

 Medically unstable

 Heart failure

 Unstable angina

 Child bearing

 Lactating

 Not a surgical candidate

 Any contraindication per MRI Screening Form (Appendix A attached). This is the same form used in clinical practice at UT Southwestern.

 Titanium implants, pacemakers

 Poorly controlled diabetes

 Body weight greater than 300 pounds

 Claustrophobic

 Since each patient is receiving a gadolinium based contrast agent intravenously:

 eGFR < 45 mL/min/1.73m2

 Sickle cell disease

 Hemolytic anemia


Individualized Prevention Strategy for High Risk Patients in Cardiovascular Disease: Prospective Cohort Study (Cardiovascular and Metabolic Disease Etiology Research Center - HIgh Risk Cohort) CMERC-HI

Summary: Set the prospective cohort (CMERC-HI) to study the known and novel etiologies and related factors for predicting clinical outcomes in Korean patients with high risk cardiovascular disease.
Inclusion criteria: inclusion criteria:

 high risk hypertension patients a. eGFR > 60 with one of target organ damages b. eGFR <= 60

 diabetes mellitus with microalbumin ration (AC ratio >= 30mg/g)

 anuric ESRD patients on dialysis

 the relatives of acute myocardial infarction patients under 55 years old (men)/ 65 years old (women)

 atherosclerotic cardiovascular disease (abdominal aorta diameter ≥3 cm or ankle-brachial index <0.9, or carotid plaque or carotid intima-media thickness ≥0.9 mm, or asymptomatic old cerebrovascular accident, or >30% stenosis in at least one major coronary artery)

 rheumatoid arthritis patients aged > 40 years on MTX and steroid therapy

 atrial fibrillation patients with CHADS-VASc Score ≥ 1

 kidney transplant recipient at > 3 months after transplantation

Exclusion criteria: :

 acute myocardial infarction, acute coronary syndrome patients, symptomatic coronary artery disease or history of these diseases

 symptomatic peripheral artery disease, heart failure and history of these diseases

 desired life time under 6 months due to non-cardiovascular disease (e.g. cancer, sepsis)

 women with pregnancy or on nursing

 history of contrast allergy and related side effects

 within the first three months after transplantation

 acute renal allograft rejection

['High Risk Cardiovascular Disease Patients']


Usability of the CollaGUARD Adhesion Barrier Following Hysteroscopic Adhesiolysis

Summary: Assess the feasibility of CollaGUARD following Hysteroscopic Adhesiolysis.
Inclusion criteria: inclusion criteria:

 Diagnosed with intrauterine adhesions and found eligible for hysteroscopic adhesiolysis

 Willing to use additional contraception throughout study

Exclusion criteria: :

 Be pregnant or having a suspected molar pregnancy, lactating, or planning to become pregnant at any time during the study

 Has suffered or currently suffers from a gynaecological malignancy

 Has undergone a previous hysteroscopic surgery (such as removal of fibroids)


D-dimer to Select Patients With First Unprovoked Venous Thromboembolism Who Can Have Anticoagulants Stopped at 3 Months

Summary: The purpose of this study is to determine if the risk of recurrent venous thromboembolism (VTE) after stopping therapy is low and acceptable in patients with a first unprovoked proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) who have completed 3 months of therapy and who have a negative D-dimer test on therapy and 1 month after stopping therapy.
Inclusion criteria: inclusion criteria:

 Be >= 18 years of age

 Have had ONE episode of unprovoked proximal DVT and/or PE

 Have completed 3 uninterrupted months of warfarin therapy (target INR of 2.0-3.0)

Exclusion criteria: :

 Another indication for long-term anticoagulation (e.g., atrial fibrillation)

 A high risk of bleeding as evidenced by any of the following:

 Age greater than 75 years

 Previous episode of major bleeding where the cause was not effectively treated

 Known chronic thrombocytopenia with a platelet count of less than 120,000 x 10^9 /L

 Known chronic renal impairment with a creatinine of more than 150 mumols /litre (1.7 mg/dl)

 Known chronic liver disease with a total bilirubin of more than 25 mumols /litre (1.5 mg/dl)

 Active peptic ulcer disease

 Poor compliance with, or control of, anticoagulant therapy during initial treatment

 Requires dual antiplatelet therapy (e.g. aspirin and clopidogrel)

 A vena caval filter

 Has had D-dimer testing performed within 2 months of potential enrollment other than for evaluation of suspected recurrent VTE that was not confirmed

 Has a life expectancy less than 5 years

 Is unable to attend follow-up visits because of geographic inaccessibility

 Is participating in a competing clinical investigation

['Discontinue anticoagulant therapy (Negative d-dimer)', 'Continue on anticoagulant therapy (positive d-dimer)']

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


Hypothermia for Cardiac Arrest in Paediatrics

Summary: The investigators hypothesized that, following cardiac arrest in pediatric patients, hypothermia therapy will improve the proportion of patients with a good functional outcome compared to a normothermic control group.
Inclusion criteria: inclusion criteria:

 Informed consent by parent or legal guardian

 Age ≥ 38 weeks gestation up to and including 17 years

 Patient admitted with a diagnosis of a cardiac arrest requiring compressions ≥3 minutes

 Remain comatose i.e. have Glasgow Coma Score less than or equal to 10 assessed at the tertiary level pediatric hospital at least 1 hour post- cardiac arrest

 Invasive mechanical ventilation

Exclusion criteria: :

 Cardiac arrest lasting ≥45 minutes, irregardless of commencement of ECMO

 Refractory hemorrhagic shock

 Dysrhythmia leading to cardiac arrest, where cooling would be part of standard therapy

 Suspected diagnosis of brain death as defined as fixed and dilated pupils, Glasgow Coma Score of 3 and no evidence of brain function on neurological examination

 Patients who have had a prolonged cardiac arrest at the scene of a trauma

 Decision to withhold (DNR) or withdraw life sustaining therapies

 Acute Birth asphyxia

 Terminal illness, not expected to survive 12 months

 Cardiac arrest caused by septic shock

 Severe neurodevelopmental disability or persistent vegetative state prior to cardiac arrest

 Near drowning in ice water and temperature <32ºC on admission to study site

 It has been more than 6 hours following cardiac arrest (estimated by first responder)

 Previous enrolment in the HypCAP Pilot Study

 Pregnant

 Parent/Guardian refuse consent

 Responsible physician refuses to enrol patient


A Prospective, Randomised Long-term Follow-up of Operative Versus Non-operative Treatment of Gr. 3 Acromioclavicular Dislocation

Summary: The purpose of this study is to compare the long-term clinical and radiological results of operative and conservative treatment of Tossy type 3 acromio-clavicular dislocation.
Inclusion criteria: inclusion criteria:

 Patient with Tossy grade 3 AC-dislocation was recruited between the years 1989 and 1991 at Kuopio University Hospital for a randomized controlled study

 A written informed consent.

Exclusion criteria: :

 Not written informed consent

['Non-surgical group', 'Surgical group']

['Acromioclavicular Joint', 'Dislocation', 'Surgical Procedures, Operative']

Acromioclavicular Joint
Dislocation
Surgical Procedures
Operative


Effect of a New High-protein Oral Supplement on Functional Parameters in Patients in Nursing Homes

Summary: The objective of this study is to determine whether a supplementation with a new high-protein oral supplement can improve the evolution of functional parameters in elderly patients in nursing homes.
Inclusion criteria: inclusion criteria:

 Man or woman aged more than 60 years old

 Living in a nursing home for at least 2 months

 Malnourished or at risk of malnutrition (MNA<23.5 or BMI<24 or albumin<35 g/l or weight loss of more than 5 kg in the last 6 months)

 Without dementia or with moderate dementia (MMSE > or =10/30)

 Able to walk without human assistance (technical assistance allowed)

 No vitamin D supplementation

 Able to follow the study procedures and agreed to consume oral supplement

Exclusion criteria: :

 Severe dementia (MMSE < 10/30)

 Enteral nutrition

 Severe renal or hepatic impairment

 Cancer with chemotherapy

 Uncontrolled diabetes

 Lactose intolerance

 Cow's milk protein allergy

['New DELICAL formula', 'Standard DELICAL formula']

New DELICAL formula
Standard DELICAL formula


Long Term Neurotoxic Effects of Chemotherapy in Survivors of Bone and Soft Tissue Sarcomas. A Retrospective Study

Summary: The aim of the proposed project is to study the long-term impact of adjuvant systemic multi- agent chemotherapy (cisplatin, anthracyclines, vincristine, methotrexate, alkylating agents) in survivors (treated between 1992 and 2014 in UZ Leuven) of paediatric bone or soft tissue sarcomas on neurocognitive functioning.
Inclusion criteria: inclusion criteria:

 Survivors of paediatric bone or soft tissue sarcomas, who were treated from 1992 onwards in the paediatric haematooncology department of UZLeuven according to one of the following treatment protocols.

 *For soft tissue sarcomas: MMT 95, MMT 98, RMS2005 or NRST2005

 *For Ewing sarcoma: EICESS 92, Euro-Ewing 99 or Euro-Ewing 2008

 *For osteosarcoma: EORTC 80931 or Euramos1 protocols

 There will be variability in treatment regimens, but the patient group will be clustered into four subgroups:

 Cisplatin and anthracyclines

 Cisplatin, anthracyclines and methotrexate

 Alkylating agents

 Alkylating agents and anthracyclines

Exclusion criteria: :

 Mental retardation documented before treatment

 Inability to perform the tests because of motor or sensory deficits

 Epilepsy

 Other cognitive disorders

 Depression

 Relapse

 Parameningeal or intracranial sarcomas

 Syndrome (e.g. Down)

 Autologous stemcell transplantation

 Head/neck/spinal radiotherapy or psychopharmaca

['Sarcoma, Soft Tissue', 'Osteosarcoma Tumor']


Freehand Ultrasound to Evaluate Scapular Kinematics in People With Paraplegia

Summary: Shoulder pain is very common in people with spinal cord injury (SCI). Persons with high-level paraplegia have higher chances to suffer shoulder pain and injury than those with lower-level paraplegia due to the shoulder muscle imbalance. As people with SCI overuse the shoulder during routine daily activities, the onset of pain or injury lead to increased healthcare expenses, limitation in activity, depression, decreased participation, and reduced quality of life. One of the main reasons of shoulder pain is believed to have a altered scapular movement. To clarify the mechanism of the shoulder pain and injury, comprehensive understanding of three-dimensional scapular kinematics is required. Ultrasound is a low-cost and non-invasive imaging system and has been used to diagnose the shoulder pain and injury in individuals with SCI. A freehand ultrasound (FUS) combining ultrasound with motion capture system to evaluate scapular movement was developed and presented favorable results in able-bodied population. The purpose of this study is to compare the FUS and widely used skin-based method against a radiographic based gold standard in people with paraplegia, and to elucidate the relationship among scapular movement and shoulder pain, pathology. This study will also allow us to gain more understanding of how level of injury influences the scapular behavior during functional activities. The investigators believe more severe shoulder pain and pathology will be associated with greater abnormal scapular movement. The investigators also believe that people with high-level paraplegia will have greater scapular abnormality than people with low-level paraplegia during arm elevation and weight relief raise tasks. By completing this study, the investigators will expect to deliver a reliable and valid tool to evaluate scapular movement and gain a better understanding how the altered scapular movement is related to shoulder pain and pathology. The investigators will also learn how the level of injury affects the scapular behavior during functional activities. The results of this study may help the shoulder pain management leading to the improvement in the quality of life of individuals with SCI.
Inclusion criteria: inclusion criteria:

 Above 18 years old

 Have paraplegia as a result of a spinal cord injury morn than one year;

 Able to perform push-ups independently and raise the arm above the head;

 Self-propel a manual wheelchair as the primary means of mobility

Exclusion criteria: :

 Have history of fractures or dislocations in the shoulder, elbow, or wrist from which you have not fully recovered;

 Have upper limb pain as a result of a complex regional pain syndrome;

 Have a implant or pacemaker within the torso or upper arm;

 Pregnant female.

['Spinal Cord Injuries', 'Shoulder Impingement Syndrome']

Spinal Cord Injuries
Shoulder Impingement Syndrome


Effect of Curodont™ Repair in Patients With Early Approximal Carious Lesions

Summary: The purpose of this study is to evaluate the therapeutic benefit of Curodont Repair for the treatment of early approximal carious lesions compared to fluoride.
Inclusion criteria: inclusion criteria:

 Two approximal carious lesions on different teeth with at least one tooth in between

 Both study lesions must not require an invasive treatment

 Size and form of the lesions: the lesions must be fully visible and assessable on radiographs

 The two carious lesions must fall into classes:

 D2 (inner half of enamel)

 D3 (outer part of dentine) but only if very little dentine is involved (enamel-dentine junction)

 Able and willing to observe good oral hygiene throughout the study

 Age ≥ 18 years and ≤ 65 years

 Willing and able to attend the on-study visits

 Willing and able to understand all study-related procedures

 Written informed consent before participation in the study

Exclusion criteria: :

 The two study test lesions are located on adjacent teeth

 Fluoride varnish application < 3 months prior to study treatment

 Tooth with numerous carious lesions

 Evidence of tooth erosion

 History of head and neck illnesses (e.g. head/neck cancer)

 Any pathology or concomitant medication affecting salivary flow or dry mouth

 Any metabolic disorders affecting bone turnover

 Patient suffers from diabetes

 Concurrent participation in another clinical trial

 Women who are breast-feeding, pregnant or who plan a pregnancy during the study

 Women of childbearing potential who declare being unwilling or unable to practice contraception such as hormonal contraceptives, sexual abstinence or intercourse with a vasectomised partner


Risperidone vs. Bupropion ER Augmentation of SSRIs in Treatment-Resistant Depression

Summary: The purpose of this study is to evaluate the comparative effectiveness of Risperdal (risperidone) or bupropion ER (extended release) combined with a SSRI medication and to test the relative safety of the combinations.
Inclusion criteria: inclusion criteria:

 Male or female 18 years or older

 DSM-IV diagnosis of major depressive disorder of at least moderate severity, but without psychotic features

 Ham-D 17 score of 18 or above

 Have a documentable history of 2 prior adequate trials of antidepressants including an SSRI without sufficient response. A clinically adequate trial is defined as having taken a minimum effective dose of an antidepressant for at least 3 weeks without a significant change in depressive symptoms.

 Must be currently on an serotonin uptake inhibitor (to include venlafaxine or duloxetine) at an adequate dose for at least 3 weeks.

 Ability and willingness to provide consent for participation in the study.

Exclusion criteria: :

 Any medical condition that would preclude treatment with an SSRI, risperidone, or bupropion ER

 Any clinically significant unstable medical condition

 Diagnosis of bipolar disorder or a primary diagnosis of any psychotic disorder

 Current psychotic symptoms (hallucination or delusions)

 Alcohol or drug abuse or dependence in the last 3 months (excluding nicotine and caffeine dependence/abuse) or abuse within the last month

 Documented non-response to the combination of a novel antipsychotic or bupropion ER and a SSRI

 Concomitant use of any psychotropic other than an SSRI or zolpidem (PRN for sleep)

 Score of 4 on the suicide item of the Ham-D scale and determination by the investigator of significant suicide risk

 Known sensitivity to risperidone or bupropion ER

['Rispridone (drug) and Bupropion ER (drug)']


Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure

Summary: This is a 26-week, prospective double-blind, randomized pilot trial of nebivolol versus an active control, metoprolol succinate, in patients with established lower-extremity peripheral artery disease, hypertension, and at least moderate risk for coronary artery disease.
Inclusion criteria: inclusion criteria:

 Men and non-pregnant, non-lactating women 45 years of age or older

 Able to give informed consent and complete scheduled visits

 Mild-moderate bilateral lower extremity peripheral arterial disease as defined by an ankle-brachial index (ABI measurement of 0.6-0.9. If a subject has baseline claudication symptoms, the symptoms must be stable for the 3 months preceding enrollment.

 History of hypertension. Blood pressure at the screening visit must be ≤160/100 mmHg and ≥100/60 mmHg for all subjects. If a subject is currently prescribed beta-blocker therapy, BP at the screening visit must be ≤140/90 mmHg. In addition, heart rate must be ≥55 beats per minute if currently prescribed a beta-blocker and ≤60 beats per minute if not currently prescribed a beta-blocker.

 At least moderate risk for CAD.

Exclusion criteria: :

 Participation in another clinical trial

 Ongoing ischemic (resting) limb pain, or lower extremity ulceration due to arterial insufficiency, or an ABI indicating <0.6 indicating disease potentially requiring revascularization

 History of limb or digit amputation due to arterial insufficiency

 Revascularization of peripheral vessels within the preceding 6 months

 Uncontrolled hypertension as defined by systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg

 Contraindication or allergy to beta blocker therapy

 History of myocardial infarction , coronary revascularization, or a cerebrovascular event within the preceding 6 months

 Class III or IV angina

 Current or past history of New York Heart Association (NYHA) class III or IV heart failure

 Inability to walk on a treadmill for any reason

 Regular use of nitroglycerin or nitrates including oral, transdermal ointment or patch, or sublingual, translingual spray and/or combination agents containing nitrates

 Active liver, pulmonary, infectious or inflammatory process

 History of malignancy within preceding 5 years (excluding basal or squamous cell skin cancer)

 History of any other condition that, in the opinion of the investigators, renders it unsafe for the subject to be enrolled

['Peripheral Artery Disease', 'Hypertension']