Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA)

Summary: The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis who have not been previously treated with DMARDs.~Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.
Inclusion criteria: inclusion criteria:

 Subjects must satisfy the following criteria to be enrolled in the study:

 Male or female, aged ≥ 18 years at time of consent.

 Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.

 Able to adhere to the study visit schedule and other protocol requirements.

 Have a documented diagnosis of Psoriatic Arthritis (PsA, by any criteria) of ≥ 3 months duration.

 Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA at time of screening.

 Have ≥ 3 swollen AND ≥ 3 tender joints.

 Have not been previously treated with disease-modifying antirheumatic drugs (DMARDS) (small molecules or biologics)

 Be receiving treatment on an outpatient basis.

 If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 1 month prior to screening.

 If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 24 study visit.

 Low potency topical corticosteroids (Appendix M or locally available equivalent) will be allowed as background therapy for treatment of psoriasis on the face, axillae and groin in accordance with the manufacturers' suggested usage during the course of the study. Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. A non-medicated skin emollient (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not use these treatments within 24 hours prior to the clinic visit.

 Meet the following laboratory criteria:

 White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L)

 Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)

 Serum creatinine ≤ 1.5 mg/dL(≤ 132.6 μmol/L)

 Aspartate aminotransferase/Serum glutamic oxaloacetic transaminase (AST/SGOT) and Alanine aminotransferase/Serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2 x upper limit of normal (ULN)

 Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L)

 Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)

 Hemoglobin A1c ≤ 9.0%

 Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on IP and for at least 28 days after the last dose of IP.

 Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception while on investigational product (IP) and for at least 28 days after the last dose of IP: one highly effective form (ie, hormonal, intrauterine device [IUD], tubal ligation, vasectomized partner) and one additional form (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane], diaphragm, sponge). If one highly effective form of contraception cannot be used, then 2 forms of barrier contraception must be used, ie, latex condom or any nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane) with either of the following: sponge with spermicide or diaphragm with spermicide.

Exclusion criteria: :

 History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.

 Any condition, including the presence of laboratory abnormalities that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

 Clinically significant abnormality on 12-lead electrocardiography (ECG) at Screening.

 Pregnant or breast feeding.

 History of allergy to any component of the IP.

 Hepatitis B surface antigen positive at screening.

 Hepatitis C antibody positive at screening.

 AST/SGOT and/or ALT/SGPT > 1.5 x ULN and total bilirubin > ULN or albumin < lower limit of normal (LLN).

 History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).

 Active tuberculosis or a history of incompletely treated tuberculosis.

 Clinically significant abnormality based upon chest radiograph with at least PA view (radiograph must be taken within 12 weeks prior to Screening or during the Screening visit). An additional lateral view is strongly recommended but not required.

 Active substance abuse or a history of substance abuse within 6 months prior to Screening.

 Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed at least 4 weeks prior to Screening.

 Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix).

 Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.

 Erythrodermic, guttate, or pustular psoriasis.

 Topical therapy for psoriasis, except as noted in the inclusion criteria, within 2 weeks of randomization (including but not limited to topical corticosteroids, topical retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin).

 Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, or polymyositis.

 Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix Q).

 Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease).

 Prior use of disease modifying antirheumatic drugs (DMARDS; small molecules or biologics).

 Use of the following systemic therapy(ies) within 4 weeks of randomization, including but not limited to corticosteroids (except as noted in inclusion criteria), oral retinoids and fumaric acid esters.

 Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA).

 Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20).

 Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column within 6 months of baseline.

 Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.

 Prior treatment with apremilast.

 Use of any investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/ pharmacodynamic half lives, if known (whichever is longer).

['Apremilast 20mg', 'Apremilast 30mg', 'Placebo']


Improve the Treatment of Thoracic Esophageal Cancer

Summary: The purpose of this study is~To compare the effects of the two types of thoracic esophageal cancer lymphadenectomy on the staging and prognosis of resectable esophageal cancer, which defined by the International Association of esophageal disease(ISDE) - standard mediastinal lymphadenectomy,total mediastinal lymphadenectomy and three field lymphadenectomy,and to find out reasonable range of lymphadenectomy.~To compare the effects of Chemotherapy Group (Docetaxel + Nedaplatin) with Control Group on the prognosis of resectable thoracic esophageal cancer,and to explore the indications of adjuvant chemotherapy.
Inclusion criteria: inclusion criteria:

 Age≤70 years old;

 Karnofsky Performance Status（KPS）≥80;

 Pathological diagnosis is squamous cell carcinoma of thoracic esophageal which is treated initially;

 Clinical stage is c T 1

  3 N 0

  1 according to the results of endoscopic ultrasonography，chest and abdomen CT and neck ultrasonic.

 The preoperative evaluation of organ function is tolerant of surgery and chemotherapy;

 The subject can understand and sign the informed consent form (ICF);

 The following laboratory tests, made in 4 weeks before first medication, confirmed that bone marrow, liver and kidney function in line with the requirements to participate in research; Hemoglobin（HGB）≥9.0g/L; absolute neutrophils count（ANC）≥1.5×109/L; platelet count（PLT）≥100×109/L; total bilirubin（TBIL）≤1.5N;aspartate aminotransferase (AST)≤2.5N;alanine aminotransferase(ALT)≤2.5N;prothrombin time(PT)≤1.5N, and activated partial thromboplastin time(APTT) is in normal range;endogenous creatinine clearance rate(CRE)≤1.5N.

Exclusion criteria: :

 Cervical esophageal cancer and Non-squamous cell carcinoma of thoracic esophageal cancer;

 Advanced Esophageal Cancer;

 Prior malignancy in 5 years recently;

 History of previous chest radiotherapy;

 History of cardio-cerebral vascular accident in 6 months lately;

 The subject can not understand and sign the informed consent form(ICF).

['adjuvant chemotherapy', 'standard two field Lymphadenectomy', 'Total two field Lymphadenectomy', 'three field Lymphadenectomy']

adjuvant chemotherapy
standard two field Lymphadenectomy
Total two field Lymphadenectomy
three field Lymphadenectomy

['Thoracic Esophageal Squamous Cell Carcinoma']


Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Doses of Zolpidem in Children

Summary: This is a multicenter trial to evaluate the single-dose safety, tolerability and pharmacokinetics-pharmacodynamics of Zolpidem in a group of children with sleep disturbances stratified by age and dose.
Inclusion criteria: inclusion criteria:

 Male or female between the ages of 2 years and 18 years.

 Written consent must be obtained form the parent/legal guardian for all minors. Written assent must be obtained from all minors > 6 years of age.

 Female subjects of child-bearing potential must not be pregnant and if females are fertile and sexually active, must have documented a negative urine HCG and assure use of effective contraception acceptable to the investigator (abstinence accepted) during the study period.

 Subjects must meet the following criteria for a diagnosis of insomnia as determined by the subject's private physician or study investigator and subject's history:

 the complaint is significant difficulty (defined by frequency, severity, and/or chronicity) initiating or maintaining sleep;. The problem is viewed problematic by the child and/or caregiver;

 the sleep disturbance causes clinically significant impairment in school performance, behavior, learning, or development for the child as reported by the child and/or caregiver;

 the sleep disturbance does not occur exclusively in the context of an intrinsic dyssomnia such as narcolepsy, restless legs syndrome, or sleep-related breathing disorders; a circadian rhythm disorder; or a parasomnia;

 the sleep disturbance is not attributable to either the direct physiologic effect of a drug of abuse or misuse of a prescribed medication.

Exclusion criteria: :

 Pregnancy and/or breastfeeding;

 The presence of any untreated (where treatment is available), or unstable, progressive, or evolving clinically significant renal, endocrine, hepatic, respiratory, cardiovascular, neurologic, hematologic, immunologic, cerebrovascular disease or malignancy;

 Elevations in screening blood tests of renal (SCr) and liver (ALT, AST and/or bilirubin) > 2 times the upper limit of normal for age.

 Receiving any medications that may modulate Zolpidem metabolism, primarily drugs that will enhance or reduce the activity of CYP450 3A, 2C9, or 2D6 activity. Note: If patient is receiving a medication that might be considered an inducer or an inhibitor, please discuss with the PI prior to excluding them.

 Receiving any medications with sleep-impairing properties at a dose/dose interval that would be judged by the study investigator as to interfere with the assessment of Zolpidem sleep response.

 Currently using any systemic contraceptive steroids including: oral contraceptives, transdermal patch, vaginal insert, levonorgestrel implant and medroxyprogesterone acetate contraceptive injection.


Norwegian Adenomyosis Study III: Peristalsis

Summary: Spontaneous contractions (peristalsis) of the non-pregnant uterus is widely investigated and the role of correct peristalsis is most important for correct sperm transport towards the fallopian tubes and implantation of the embryo, thus obtaining pregnancy. At the same time, an impaired uterine peristalsis is discussed to be the reason for lower pregnancy rates and may also account for heavy menstrual bleedings and menstrual pain.~In this study, the uterine peristalsis of women with adenomyosis will be investigated. This condition is associated to heavy menstrual bleeding, menstrual pain and infertility.
Inclusion criteria: inclusion criteria:

 Premenopausal women aged 20-45 years having been diagnosed with adenomyosis earlier and have no other pathology of the uterus, regardless of clinical symptoms.

Exclusion criteria: :

 Postmenopausal women,

 Pregnant women,

 Gynaecological cancer,

 GnRH analog therapy or systemic hormone therapy in the last three months prior to hysterectomy,

 Endometriosis,

 Uterine fibroids


Management of Acute Myocardial Infarction in the Presence of Left Bundle Branch Block

Summary: The primary objective of this study is to propose new treatment algorithm (strategy) for patients with Acute Coronary Syndrome (ACS) and left bundle-branch block (LBBB).
Inclusion criteria: inclusion criteria:

 Age 18 - 75 years

 Ischemic discomfort (ie, ischemic chest pain or equivalent) at rest ≥20 minutes within previous 24 hours.

 Any (new, presumably new, or old) LBBB on the prehospital (ambulance) or admission ECG.

 Urgent coronary angiography (followed, when indicated, by PCI), ideally within 90 minutes after admission

Exclusion criteria: :

 all-comers design


Reducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics

Summary: This study will test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications.
Inclusion criteria: inclusion criteria:

 DSM diagnoses that have an FDA indication for atypical antipsychotic use for at least one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV diagnosis of Early Onset Schizophrenia Spectrum (EOSS; schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder NOS); Bipolar Spectrum (bipolar I, II and NOS); Major depressive disorder with psychosis; Mood disorder NOS corresponding to Leibenluft and colleagues severely mood dysregulated (SMD) broad spectrum bipolar disorder; Mood disorder NOS corresponding to irritability associated with autism spectrum disorders; or - for adult teen participants aged 18-19 years - Major depressive disorder. Diagnoses will be determined by clinical interview, Leibenluft's modification of the K-SADS-PL, and the Aberrant Behavior Checklist (cutoff score of 18, as used by FDA for approval of risperidone and aripiprazole in minors).

 Clinically stable on current treatment regimen for at least 30 days, as assessed in a three-step process

 Current SGA treatment with olanzapine, quetiapine, risperidone, ziprasidone aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine for ≥ 8 weeks

 Stable dose of current SGA and psychotropic co-medications for at least 30 days

 Body mass index (BMI) at least in the 85th percentile for age and gender

 Substantial weight gain over the previous 3 years while taking a SGA, as reflected by family and referring physician's judgment. The weight gain did not have to occur on the child's current SGA. Weight needs to have remained stable or increased over past year.

 Agrees to use two effective forms of birth control or to remain abstinent

 Has a primary caretaker who has known the child well for at least 6 months before study entry

 Primary caretaker is able to participate in study appointments as clinically indicated

Exclusion criteria: :

 Treatment with any medication (other than the currently prescribed psychotropic medications) that would significantly alter glucose, insulin, or lipid levels. Exception: orlistat and amantadine are permitted if the individual has taken the drug for at least one year without weight loss.

 Major neurological or medical illness that affects weight gain or that would prevent participation in physical activities

 Fasting glucose levels indicating need for prompt treatment

 Pediatrician or pediatric gastroenterologist recommendation to address abnormal fasting labs by pursuing more active treatment than those in the 2007 American Medical Association guidelines

 Diagnosis of anorexia nervosa or bulimia nervosa, as based on current or lifetime DSM-IV criteria

 Diagnosis of substance dependence disorder (other than tobacco dependence) within the past month, as based on DSM-IV criteria

 Positive urine toxicology indicating ongoing use of illicit substance

 Current treatment with more than one antipsychotic medication

 Current treatment with more than 3 total psychotropic medications (i.e., 2 psychotropics plus SGA), with the exception of subjects taking 2 medications for ADHD in which a total of 4 psychotropic medications are allowed.

 Known hypersensitivity to metformin

 Prior treatment with aripiprazole and perphenazine for more than 2 weeks that was stopped for inefficacy or intolerability

 Pregnant, breastfeeding, or unwilling to comply with contraceptive requirements of study

 IQ score less than 55

 Significant risk of dangerousness to self or to others that would make study participation inadvisable

 Language issues that prevent child and/or parent from completing assessments or treatment

 Ongoing or previously undisclosed child abuse requiring new department of social service intervention

['Aripiprazole or Perphenazine', 'Metformin', 'Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine']

Aripiprazole or Perphenazine
Metformin
Olanzapine
quetiapine
risperidone
ziprasidone
aripiprazole
asenapine
iloperidone
lurasidone
paliperidone
or olanzapine/fluoxetine


Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

Summary: The purpose of this ascending-dose research study is to determine whether the administration of ARC1779 Injection improves subject's health profile by protecting the brain, heart, and kidney from damage due to formation of small blood clots in blood vessels. It will also determine the safety of ARC1779 Injection, how ARC1779 Injection enters and leaves the blood and tissue over time, and its effect on laboratory tests related to blood clotting, heart and brain function, and other body systems.
Inclusion criteria: inclusion criteria:

 Male or female;

 ≥18 to ≤75 years of age;

 Diagnosis of TMA based on presence of:

 Thrombocytopenia, defined as a platelet count <100 x 109 per liter;

 Microangiopathic hemolytic anemia, defined by negative findings on direct antiglobulin test, and evidence of accelerated red blood cell (RBC) production and destruction); AND

 Absence of a clinically apparent alternative explanation for thrombocytopenia and anemia, e.g., disseminated intravascular coagulation (DIC), eclampsia, HELLP syndrome, Evans syndrome;

 Females: non-pregnant and commit to use of effective, redundant methods of contraception (i.e., for both self and male partner) throughout the study and for at least 30 days after discontinuation of study drug treatment;

 Males: commit to use of a medically acceptable contraceptive (abstinence or use of a condom with spermicide) throughout the study and for at least 30 days after discontinuation of study drug treatment;

 Not received an unlicensed investigational agent (drug, device, or blood-derived product) within 30 days prior to randomization, and may not receive such an investigational agent in the 30 days post-randomization (note: investigational use for treatment of TMA of a licensed immunomodulator, e.g., rituximab, is permitted at any time relative to randomization);

 Capable of understanding and complying with the protocol, and he/she (or a legal representative) must have signed the informed consent document prior to performance of any study-related procedures.

 Patients who have again become acutely ill following recent treatment and achievement of a brief remission of acute TMA may be enrolled in the study if ALL of the following conditions are met:

 Disease activity in the patient in unabated (e.g. persistent thrombocytopenia and microangiopathic hemolytic anemia with ongoing neurological symptoms and/or troponin elevation);

 The last plasma exchange of the patient's preceding course of treatment occurred at least 7 days prior;

 The patient did not undergo splenectomy during the preceding course of treatment;

 The new course of plasma exchange has not been ongoing for more than 3 days.

Exclusion criteria: :

 Females: pregnant or <24 hours post-partum, or breastfeeding;

 History of bleeding diathesis or evidence of active abnormal bleeding within the previous 30 days;

 Disseminated malignancy or other co-morbid illness limiting life expectancy to ≤3 months independent of the TMA disorder.

 Diagnosis other than TMA which can account for the findings of thrombocytopenia and hemolytic anemia (e.g., DIC, HELLP syndrome, Evans syndrome);

 Diagnosis of DIC verified by laboratory values for D-dimer, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT).

 Patients who have again become acutely ill following recent treatment and achievement of a brief remission of acute TMA may not be enrolled in the study if ANY of the following conditions are met:

 The last plasma exchange of the patient's preceding course of treatment occurred less than 7 days prior;

 The patient underwent splenectomy during the preceding course of treatment;

 The new course of plasma exchange has been ongoing for more than 3 days.

['ARC 1779 Placebo', 'ARC1779 Injection', 'ARC1779 Injection', 'ARC1779 Injection']

ARC 1779 Placebo
ARC1779 Injection
ARC1779 Injection
ARC1779 Injection

['Thrombotic Microangiopathy', 'Thrombotic Thrombocytopenic Purpura']

Thrombotic Microangiopathy
Thrombotic Thrombocytopenic Purpura


Study of Aspirin and TPA in Acute Ischemic Stroke

Summary: This study will determine the safety of 500mg of aspirin added to IV TPA at standard doses to prevent re-occlusion of cerebral vessels after successful reperfusion. In ischemic stroke brain arteries are occluded either by an embolus originating in the heart or large vessels leading to the brain or by a process of acute thrombosis of the cerebral arteries over a ruptured atherosclerotic plaque. Rupture of the plaque exposes thrombogenic elements within the plaque and leads to accumulation and activation of platelets and induction of the clotting cascade eventually leading to acute thrombosis and occlusion of the artery. TPA is currently approved by the Food and Drug Administration to treat heart and brain problems caused by blockage of arteries. It activates plasminogen and leads to disintegration of the thrombus/embolus. It is effective only if begun within 3 to 4.5 hours of onset of the stroke because of potential deleterious side effects including life threatening symptomatic intracranial hemorrhage (sICH) when the drug is administered outside of this time window.~Reperfusion of the ischemic brain (i.e. timely opening of the occluded artery) with TPA is associated with improved outcome. However, in about 33% of patients that have successfully reperfused after TPA the artery re-occludes within the first few hours resulting in worsening neurological symptoms and worse functional outcome. This re-occlusion is speculated to result from re-thrombosis over an existing ruptured atherosclerotic plaque. This is explained by the relatively short half life of TPA leaving the exposed ruptured plaque intact which leads to re-activation of platelets and clotting factors and re-thrombosis. Thus, we hypothesize that the addition of an antiplatelet agent to TPA would result in lower rates of re-occlusion after AIS. The FDA approved TPA for patients with AIS but discouraged the concomitant use of anti-platelet or anti-thrombotic drugs for the first 24hours after administration of TPA because of concerns that such therapy may result in increased rates of intracerebral hemorrhage. Aspirin is a well known platelet anti-aggregant that works by inhibition of cycloxygenase 1 and reduction in thromboxane A levels. It has a rapid onset of action and additional potential beneficial anti-inflammatory effects in patients with AIS. The international stroke study showed that acute treatment of stroke patients with 500mg of aspirin is safe and feasible and results in better outcome. Furthermore, the drug was safe in these circumstances with an ICH rate of only .~Therefore, the purpose of this clinical trial is to examine the safety and efficacy of the combination of aspirin with rt-TPA in patients with AIS.
Inclusion criteria: inclusion criteria:

 Patients must meet all of the inclusion criteria.

 Diagnosis of acute ischemic stroke with onset less than 4.5 hours prior to the planned start of intravenous alteplase. Acute ischemic stroke is defined as a measurable neurological deficit of sudden onset, presumed secondary to focal cerebral ischemia. Stroke onset will be defined as the time the patient was last known to be without the new clinical deficit. Patients whose deficits have worsened in the last 4.5 hours are not eligible if their first symptoms started more than 4.5 hours before. If the stroke started during sleep, stroke onset will be recorded as the time the patient was last known to be at baseline.

 Disabling neurological deficit attributable to acute ischemic stroke in the middle cerebral artery territory.

 NIHSS less than or equal to 18 for left hemisphere strokes, NIHSS less than or equal to 16 for others.

 Evidence of MCA occlusion (stem or branch) prior to drug administration by TCD, CTA or MRA.

 Age 18-85 years, inclusive.

 Able to sign informed consent.

 For MRI Arm only:

 Screening MRI diagnostic of focal cerebral ischemia corresponding to the clinical deficits. The MRI evaluation must involve echo planar diffusion weighted imaging, MRA, and MRI perfusion. A normal appearing MRA with an appropriate perfusion deficit is eligible. An apparent stenosis or occlusion on MRA with normal appearing perfusion distally will not be eligible. Poor quality or uninterpretable MRA will not make patient ineligible. Patients who have a normal appearing DWI are eligible.

 Evidence on PWI MRI or a perfusion defect corresponding to the acute stroke syndrome. The PWI will be assessed by relative mean transit time (MTT) images obtained prior to the start of rt-TPA therapy.

Exclusion criteria: :

 Patients will be excluded from study participation for any of the following reasons:

 Current participation in another study with an investigational drug or device within, prior participation in the present study, or planned participation in another therapeutic trial, prior to the final (day 30) assessment in this trial.

 Absence of acoustic window to insonate the MCA on the involved side.

 Time interval since stroke onset of less than 3 hours is impossible to determine with high degree of confidence.

 Symptoms suggestive of subarachnoid hemorrhage, even if CT or MRI scan is negative for hemorrhage.

 Evidence of acute myocardial infarction defined as having at least two of the following three features: 1) Chest pain suggestive of cardiac ischemia; 2) EKG findings of ST elevation of more greater than 0.2 mV in 2 contiguous leads, new onset left bundle branch block, ST segment depression, or T-wave inversion; 3) Elevated troponin I.

 Acute Pericarditis.

 Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.

 Neurological deficit that has led to stupor or coma (NIHSS level of consciousness [item I a] score greater than or equal to 2).

 High clinical suspicion of septic embolus.

 Minor stroke with non-disabling deficit or rapidly improving neurological symptoms.

 Baseline NIHSS greater than 18 for left hemisphere stroke or greater than 16 for others.

 Evidence of acute or chronic ICH by head CT or MRI.

 CT or MRI evidence of non-vascular cause for the neurological symptoms.

 Signs of mass effect causing shift of midline structures on CT or MRI.

 Persistent hypertension with systolic BP greater than 185 mmHg or diastolic BP greater than 110 mmHg (mean of 3 consecutive arm cuff readings over 20-30 minutes), not controlled by antihypertensive therapy or requiring nitroprusside for control.

 Anticipated need for major surgery within 72 hours after start of study drugs, e.g., carotid endarterectomy, hip fracture repair.

 Any intracranial surgery, intraspinal surgery, or serious head trauma (any head injury that required hospitalization) within the past 3 months.

 Stroke within the past 3 months.

 History of ICH at any time in the past.

 Major trauma at the time of stroke, e.g., hip fracture.

 Blood glucose greater than 200 mg/dl.

 Presence or history of intracranial neoplasm (except small meninigiomas) or arteriovenous malformation.

 Intracranial aneurysm, unless surgically or endovascularly treated more than 3 months before.

 Seizure at the onset of stroke.

 Active internal bleeding.

 Major hemorrhage (requiring transfusion, surgery or hospitalization) in the past 21 days.

 Major surgery, serious trauma, lumbar puncture, arterial puncture at a non-compressible site, or biopsy of a parenchymal organ in last 14 days. Major surgical procedures include but are not limited to the following: major thoracic or abdominopelvic surgery, neurosurgery, major limb surgery, carotid endarterectomy or other vascular surgery, and organ transplantation. For non-listed procedures, the operating surgeon should be consulted to assess the risk.

 Presumed or documented history of vasculitis.

 Known systemic bleeding or platelet disorder, e.g., von Willebrand's disease, hemophilia, ITP, TTP, others.

 Platelet counts less than 100,000 cells/micro L.

 Congenital or acquired coagulopathy (e.g., secondary to anticoagulants) causing either of the following:

 Activated partial thromboplastin time (aPTT) prolongation greater than 2 seconds above the upper limit of normal for local laboratory, except if due to isolated factor XII deficiency.

 INR greater than or equal to 1.4. Patients receiving warfarin prior to entry are eligible provided INR is less than 1.4 and warfarin can be safely discontinued for at least 48 hours.

 Life expectancy less than 3 months.

 Other serious illness, e.g., severe hepatic, cardiac, or renal failure; acute myocardial infarction; or complex disease that may confound treatment assessment.

 Severe renal failure: Serum creatinine greater than 4.0 mg/dL or dependency on renal dialysis.

 AST or ALT greater than 3 times the upper limit of normal for the local laboratory.

 Treatment of the qualifying stroke with any thrombolytic, anti-thrombotic or GPIIbIIIa inhibitor outside of this protocol.

 Any administration of a thrombolytic drug in the prior 7 days.

 Treatment of the qualifying stroke with intravenous heparin unless aPTT prolongation is no greater than 2 seconds above the upper limit of normal for local laboratory prior to study drug initiation.

 Treatment of the qualifying stroke with a low molecular weight heparin or heparinoid.

 Known hypersensitivity to TPA.

 Anticoagulation (evidenced by abnormal INR, aPTT, or platelet count) caused by herbal therapy.

 FOR non-MRI arm only (#42-43):

 Ischemic changes on screening CT of greater than approximately one third of the territory of the middle cerebral artery territory by qualitative assessment.

 Patients who were excluded by screening MRI, except for exclusions #45 (contraindication to MRI) and #46 (PWI was not obtained or is uninterpretable) and #50 (MRI not obtainable because it would have put the patient out of the 3 hour time window for alteplase).

 FOR MRI arm only (#44-51):

 Contraindication to MRI scan.

 PWI not obtained or uninterpretable.

 No MTT defect corresponding to acute stroke deficit.

 DWI abnormality larger than approximately one third of the territory of the middle cerebral artery territory by qualitative assessment.

 Satellite DWI hyperintensity with corresponding hyperintensity on T2 weighted image or FLAIR in a vascular territory different than the index stroke (this is evidence of a new ischemic lesion greater than 3 hours in duration).

 Evidence of multiple microbleeds on gradient echo MRI (GRE).

 MRI not obtained because it would have put the patient out of the 3 hour time window for alteplase.


Enhancing Father's Ability to Support Their Preschool Child

Summary: This study focuses on the development of the Fathers Supporting Success in Preschoolers (FSSP) Program, which combines evidence-based parenting interventions with Dialogic Reading to engage fathers in and improve parenting and child behavior.
Inclusion criteria: inclusion criteria:

 Male Guardian

 Child enrolled in partnering Head Start site

Exclusion criteria: :

 Mental Health issues that prohibit involvement in group-based prevention study (e.g., psychosis)

['Fathers Supporting Success in preschoolers']

['Fathers', 'Parenting', 'High-risk', 'Child Maltreatment', 'Prevention']

Fathers
Parenting
High-risk
Child Maltreatment
Prevention


Constraint-Based Therapy to Improve Motor Function in Children With Cerebral Palsy

Summary: Pediatric Constraint-Induced (CI) Movement therapy is a rehabilitation program designed to improve motor function in children with partial paralysis. Children with cerebral palsy may have one arm that has significantly greater function (good arm) than the other (bad arm). Restricting the use of the good arm may improve the use of the bad arm. In pediatric CI therapy, the good arm is put in a sling to force increased use of the bad arm. The bad arm is also trained each day for several weeks. This study will test the ability of pediatric CI therapy to improve motor function in children with cerebral palsy.
Inclusion criteria: inclusion criteria

 Clinical diagnosis of hemiparetic cerebral palsy consistent with criteria in Swaiman and Russman (1999) and Badawi et al. (1998)

 Recommended for participation in pediatric rehabilitation and/or early intervention

 Lives within 50 miles of the Civitan Center at University of Alabama at Birmingham or the family is willing to temporarily relocate to the Birmingham area for treatment

Exclusion criteria:

 Profound bilateral hearing loss with the use of hearing aids

 Severe visual impairment

 Serious seizure disorder or uncontrolled seizures

 Genetic and syndromic conditions historically excluded for CP registries

 Familial Spastic Paraplegia

 Ataxic Cerebral Palsy

 Diagnosis of Pervasive Developmental Disability or autism

 Serious or recurring medical complications

 Scheduled for surgery within 12 months of study entry

['Pediatric Constraint-Induced Movement therapy', 'Conventional pediatric motor rehabilitation therapy']


Protocol to Ease Acute Cephalalgia in Emergency-department

Summary: The purpose of this study is to determine if the use of a therapeutic and global protocol to relieve cephalalgia is helpful in the emergency department of Grenoble University Hospital.
Inclusion criteria: inclusion criteria:

 Complain about cephalalgia

 Age 28 to 55 years.

Exclusion criteria: :

 Fever > 38,0 °C

 History of breath disease, long term use of oxygen therapy, chronic obstructive pulmonary disease, dyspnea

 History of cranial traumatism, heart attack, cerebrovascular accident <3 month

 Inability to read or understand french.

 Pregnancy

['Recommendation to use global headache treatment protocol']


Palestinian Perineum and Birth Complication Study

Summary: In this study the investigators want to assess complications associated to pregnancy and delivery, and interventions used during labor.~Pregnancy and delivery related complications are a major health problem globally. Events during labor such as excessive bleeding, uterine rupture, emergency cesarean delivery; other instrumental deliveries and anesthesia problems are situations that potentially may lead to severe outcomes for the mother and child.~Diabetes, anemia and hypertensive disorders may also complicate both the pregnancy and delivery.~Between 60-80% of women delivering their first baby need suturing due to perineal tears (tears located to the area between the vagina and anus). Superficial perineal tears rarely cause long-term problems, but often lead to pain and discomfort immediately after birth. Deeper or severe perineal tears, involving the anal sphincter, may influence the woman's quality of life. This is mainly due to long-lasting pain, discomfort and sexual dysfunction, and the fact that obstetric anal sphincter tear is the main cause of anal incontinence. Recent clinical intervention studies have shown that the incidence of severe obstetric perineal tears may be reduced by 50-70% by introducing a bimanual support technique of the perineum. In these studies all midwives and gynecologists were trained in the bimanual support technique. When it comes to training in new medical techniques in general, some studies have shown that use of animated instructions on mobile phones may be a good alternative to the more traditional hands-on or bedside teaching methods. In a global perspective, it is important to study the efficacy of mobile units for transferring of new knowledge, especially for use in resource constrained settings.
Inclusion criteria: inclusion criteria:

 all midwives and physicians working on labor ward in the participating hospitals.

 all women giving birth in the participating hospitals.

 both genders are included in the staff, and among the newborns

Exclusion criteria: :

 no

['Education by animated training video', 'Interactive hands-on bedside training']

Education by animated training video
Interactive hands-on bedside training


Safety of Lactobacillus Rhamnosus GG ATCC 53103 (LGG) in Healthy Volunteers

Summary: This study is a single site, Phase I, masked, randomized study to evaluate the safety and tolerability of twice daily dosing of LGG (Lactobacillus GG ATCC 53103) in normal healthy adult volunteers. Study drug capsules (1x10^10 LGG/capsule or placebo) will be taken by mouth twice a day with cow's milk or soy milk on an outpatient basis. Volunteers will have study visits at baseline, 1 month, 3 months, 6 months, 7 months, and 12 months where they will be asked about any medical problems that have come up since the last study visit, have vital signs taken, review current medication use, and review any signs of potential adverse events. Blood and urine samples will also be collected at these visits, as well as throat and stool samples.~Our goal is to assess the safety and tolerability of LGG when administered to healthy adult volunteers twice a day. Assessment of safety will be determined by vital sign measurements, physical examinations, clinical laboratory tests, and from the incidence and severity of adverse events that occur during study participation. Additionally, we will assess whether LGG colonizes the throat and/or gastrointestinal tract of healthy adult volunteers and assess the effect of LGG on the bacteria that normally live in the throat and GI tract by using culture-independent techniques. Volunteers enrolled in this study will also be invited to participate in a companion genetic study that will investigate the host immune response to the bacteria in LGG.
Inclusion criteria: inclusion criteria:

 Age 18-50 years, inclusive.

 Expressed interest and ability to fulfill the study requirements.

 Be in general good health as determined by a screening evaluation within 30 days of the first dose of LGG or placebo.

 Able to ingest the study drug (LGG or placebo) dissolved in a small amount of cow's milk or soy milk orally (no feeding tube).

 Willing to prevent pregnancy - Women must agree not to become pregnant or breastfeed from the time of study enrollment until at least 3 months after the last dose of study drug. If a woman is sexually active and has no history of hysterectomy or tubal ligation, she must agree to practice an acceptable method of birth control, such as hormonal or barrier birth control. A woman is eligible if she is monogamous with a vasectomized male. Sexually active male volunteers without vasectomy must agree to use a barrier method of contraception for 3 months after the last dose of study drug.

 Willing to comply with protocol and report on compliance and side effects during study period.

 Informed consent obtained and signed prior to screening.

Exclusion criteria: :

 Consumption of supplements or food products containing LGG or probiotics 30 days prior to the start of the study or consumption of yogurt that has live and active cultures seal.

 Known or suspected allergies to probiotics, Lactobacillus, microcrystalline cellulose, gelatin, or any antibiotic that may be used to treat LGG bacteremia or infection (Ampicillin, Clindamycin, Moxifloxacin).

 Received oral or parenteral antibiotics within 4 weeks of enrollment or prescribed antibiotics on day of enrollment.

 Drug or alcohol abuse within previous 12 months.

 Major surgery or endoscopy within last 3 months.

 Daily prescription or over-the-counter medicines except for vitamins, birth control products, and hormone replacement therapy.

 Presence of any of the following:

 Abnormal vital signs or clinically significant physical findings such as murmur (other than functional), hepatosplenomegaly, jaundice, lymphadenopathy, or focal neurological deficit

 Indwelling catheter or implanted hardware/prosthetic device or feeding tube

 Febrile illness (oral temperature >37 degrees Celsius) or one or more episodes of diarrhea within 72 hours of baseline visit (first dose of study drug)

 Active bowel leak, acute abdomen, colitis, or active GI disease or history of gastric or intestinal dysmotility, slowed transit time, variable small intestinal permeability, pancreatitis, or inflammatory bowel disease

 History of Hepatitis B or Hepatitis C infections, cirrhosis, or chronic liver disease

 Underlying structural heart disease or previous history of endocarditis or valve replacement

 Immunosuppression including HIV positive, solid organ or stem cell transplant recipient, receiving any oral or parenteral immunosuppressive therapy, neutrophil count <500/mm^3, or an anticipated drop in the neutrophil count to <500/mm3

 History of cancer

 History of collagen vascular disease

 Active TB

 Women only - pregnant, planning on becoming pregnant within the next 9 months, breastfeeding, positive urine pregnancy test during screening or within 24 hours of first dose of study drug, or unwilling to undergo pregnancy testing.

 Positive drug or alcohol testing at screening or within 24 hours of first dose of study drug, or unwilling to undergo drug and alcohol testing.

 Screening laboratory tests greater than upper normal limit (ULN) or less than lower normal limit (LLN):

 White blood cell <LLN or >ULN

 Platelets <LLN

 Hemoglobin <LLN

 Creatinine >ULN

 Blood urea nitrogen >ULN

 Aspartate aminotransferase >ULN

 Alanine aminotransferase >ULN

 Alkaline phosphatase >ULN

 Bilirubin >ULN

 Glucose (nonfasting ) >109 mg/dL

 Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer participating in the study or would make it unlikely the volunteer could complete the study.

['Lactobacillus rhamnosus GG ATCC 53103', 'Placebo']

Lactobacillus rhamnosus GG ATCC 53103
Placebo


The Effects of Trazodone on Sleep Apnea Severity

Summary: In Obstructive sleep apnea (OSA), the upper airway closes over and over again during sleep. This leads to disrupted sleep (waking up during the night), daytime sleepiness, and an increased risk for developing high blood pressure. Currently, the best treatment for obstructive sleep apnea is sleeping with a mask that continuously blows air into the nose (i.e. Continuous positive airway pressure [CPAP] treatment). While CPAP treatment stops the upper airway from closing in most people, many people have difficulty sleeping with the mask in place and therefore do not use the CPAP treatment. This research study is being conducted to learn whether using a sedative will improve OSA severity by altering some of the traits that are responsible for the disorder.
Inclusion criteria: inclusion criteria for OSA Patients:

 OSA (elevated AHI).

 Age range 18-70 years.

Exclusion criteria: :

 Any known cardiac (apart from treated hypertension), pulmonary (including asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease.

 Susceptible to stomach ulcers.

 Pregnant women.

 History of hypersensitivity to Afrin, Lidocaine, trazodone and/or donepezil.

 History of bleeding diathesis and/or gastrointestinal bleeding.

 Use of any medications that may affect sleep or breathing.

 A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.

 Substantial cigarette (>5/day), alcohol (>3oz/day) or use of illicit drugs.

 More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.

 Desaturations to below 70% lasting greater than 10 seconds in duration per event on polysomnography.


Odor Management in Fungating Wounds Comparing Metronidazole and Polihexanide

Summary: For odor control malignant wounds (MW), use is 0.8% metronidazole solution - second recommendation scientific and clinical practice. But no this formulation available in Brazil , and its application to nursing steeps metronidazole tablets , diluted in saline and applied to the bed of (MW) . Thus , it is used off label for metronidazole ( tablets orally applied via  topical  - but it is not intact skin or mucosa ) , nursing and eventually manipulate the solution at bedside , and by law this power is pharmacist bedside and can not be taken .~Family antiseptic chlorhexidine was developed with the purpose of use in infected wounds called polihexanide ( PHMB ) . In Brazil is now available for hospital and home care ( 0.2 % Aquasept ® ) use. Evidence reported positive results in controlling infection of chronic wounds such as pressure ulcers . Although not tested its efficacy in odor control. Thus the study aims to compare metronidazole solution 0.8 % versus 0.2 % PHMB in odor control , where , if the results are favorable to PHMB we have a treatment option in odor control with ready to use formulation and easy access . Evaluate and compare the effectiveness of metronidazole solution 0.8% and polihexanide solution (PHMB) in odor control in MW. Aims: Evaluate and compare the time needed for odor control (reduction in days), using metronidazole and PHMB in MW (primary endpoint); Evaluate and compare the perceptions of patients, nurses and researcher on the odor MW, using metronidazole and PHMB in the MW; Evaluate and compare the pain reported by patients during dressing changes, using metronidazole and PHMB in the MW; Evaluate and compare the quality of life of patients before and after the use of metronidazole and PHMB in MW. This is a randomized, double -blind study with patients diagnosed with cancer and patients with MW with odor clinical trial . The sample consisted of 24 subjects divided into 2 groups (control - metronidazole group and experimental group - PHMB ) , recruited in one cancer hospital in the city of São Paulo (AC Camargo Cancer Center), which has as protocol description in odor control MW metronidazole . After acceptance by the subject and return the Statement of Informed Consent signed , randomization will be done .~For blinding , 0.8 % metronidazole solution will be provided by a compounding pharmacy (after stability testing of tablet diluted - and then stipulated expiration date) , and PHMB be bought from the supplier , delivered to the same compounding pharmacy which stores the PHMB in identical bottles to metronidazole ( only the responsible researcher will know to which group the subject was randomized ) .~The evaluation of the odor will be taken by 3  employees  and the patient through 3 scales at zero , four, eight and twelve days ( or earlier if classified as  odorless  by 3 reviewers and the patient ) . Two scales about painful sensations in exchange for healing , one on quality of life will be applied to the patient and a specifically on the impact of odor on the subject's life.~To meet the proposed objectives, the data will be analyzed by: Friedman test to assess the odor reduction with respect to time; Mann-Whitney (or t test) for comparison of groups and the Fisher exact test to compare proportions. Data will be presented in the form of frequency tables for categorical variables and means, standard deviations and position measurements for quantitative variables. Will also be performed non-parametric analysis of ordinal data, or parametric analysis with Generalized Estimation Equation for binomial variables, depending on the data distribution and the sample size.
Inclusion criteria: inclusion criteria:

 Age ≥ 18 years.

 Diagnosis of malignat wound with odor, regardless of location, etiology and tumor staging; well as in treatment or palliative care.

 Confirmation of participation in the study by signing the Instrument of Consent, personally or through responsible caretaker

Exclusion criteria: :

 not smell

['Polihexanide 2%', 'Metronidazole 0.8%']


Correlation Between Headaches and Septum and Nasal Mucosa Contact

Summary: Headache is the most common complaint to neurologists. In the 80´s and 90's few papers, with limited number of patients, have proposed the association between nasal septum contact and headache. The International Classification of Headaches Disorders proposed specific diagnostic criteria for this entity.~With the major use of CT scans, the contact between nasal mucosa and septum is daily observed in many patients without complaint of headache.~The purpose of this study is to determine if there is any correlation between nasal and septum mucosa contact and the prevalence of headache. The investigators hypothesized that no correlation will be found using CT scans in a large series of patients.
Inclusion criteria: inclusion criteria:

 All patients older than 18 years whom underwent sinuses or facial tomography.

Exclusion criteria: :

 Patients with clinical history of trauma


Maternal Effects of Bacterial Vaginosis (BV) Treatment in Pregnancy

Summary: The goal of this study is to examine acceptability and efficacy of 2 kinds of BV treatment among women at low risk for preterm delivery. The objectives are:~To examine the side effects and patient acceptability of oral versus intravaginal metronidazole.~To compare the efficacy of oral and intravaginal metronidazole for the treatment of BV~To study the efficacy of oral and intravaginal metronidazole for the prevention of hospital admission during the 3rd trimester, chorioamnionitis, preterm delivery, and maternal infectious morbidity.
Inclusion criteria: inclusion criteria: African American, Hispanic, Asian/Pacific Islander, Native American, and white women.

 -

Exclusion criteria: : Women with a prior preterm delivery, multiple gestation, chronic hypertension or pre-existing diabetes, antibiotic use before enrollment in the study, allergy to metronidazole, history of alcohol abuse in past year, and women under age 18.

 -

['Vaginosis, Bacterial', 'Premature Birth', 'Birth Weight', 'Chorioamnionitis']

Vaginosis
Bacterial
Premature Birth
Birth Weight
Chorioamnionitis


The Study of Spectrum of Sleep Disorders in Cirrhotic Patients and the Efficacy of Zolpidem in Cirrhotic Patients With Insomnia

Summary: All Cirrhosis liver patients (Child A/B/C) presenting to Institute of Liver and Biliary Sciences will be screened for sleep disturbance and excessive daytime sleepiness with Epworth sleep score/ Pittsburgh sleep quality index. 52 patients of clinical/ radiological/ biopsy proven cirrhosis (Child A/B) will be enrolled after ruling out possibility of psychiatric illnesses like depression and anxiety with the help of PHQ-9 / GAD-7 questionnares. Patients who are suffering with sleep disturbance as evaluated with Pittsburgh sleep quality index will undergo polysomnography and will be randomised to two groups after fulfilling all inclusion criterias. Patients in group (Group 1) will receive zolpidem 5mg at bed time daily and patients in control group will receive placebo at bed time daily. The treatment will be continued for 4 weeks. After 4 weeks enrolled patients will be reassessed with PSQI and polysomnography. All patients will be advised regarding sleep hygiene.
Inclusion criteria: inclusion criteria:

 Age 18 to 70 years

 Clinical, Biochemical, Radiological ,Histological evidence of cirrhosis of all etiology

 Child A and B cirrhosis (for intervention part)

 Cirrhosis patients giving h/o persistent sleep disturbances (PSQI≥5)

 Child A, B and C cirrhosis (for observational part)

Exclusion criteria: :

 Active alcohol intake or intake within 1 month of enrollment

 Active substance abuse or intake within 1 month of enrollment

 Known psychiatric and neurological disorders

 Patient using antidepressant, anticonvulsants, other hypnotics

 Pregnancy or lactation

 Overt hepatic encephalopathy (grade 2,3,4)

 Child C cirrhosis (for intervention part)

 Acute decompensated state of CLD (Chronic Liver Disease) - GastroIntestinal bleed, increased jaundice, HE (Hepatic Encepahlopahty) , SBP (Spontaneous Bacterial Peritonitis).

 HCC (HepatoCellular Carcinoma) with portal vein thrombosis

 Acute febrile illness/ acute infection

 Post TIPS (Transjugular Intrahepatic Portosystemic shunt)patient


Randomized Controlled Trial of Voice on Children With Vocal Nodules

Summary: The primary objective of this study is to determine the impact of voice therapy on voice-related quality of life in children age 6-10 years old with apparent vocal fold nodules, as measured by the validated Pediatric Voice-Related Quality of Life Instrument (PVRQOL)administered 4 weeks after completion of voice therapy.
Inclusion criteria: inclusion criteria

 Eligibility is contingent on the presence of apparent vocal fold nodules, which are defined as bilateral, localized, benign, superficial growths with protrusion on the medial surface of the true vocal folds at the junction of their anterior and middle thirds. This examination is based on video-stroboscopic examination, or, in rare cases, on operative microsuspension laryngoscopy. In addition, strict
Exclusion criteria:  are applied toward excluding masses that are not nodules. Defining characteristics for these inclusion criteria are based upon the evaluations of three senior otolaryngologists of each participant's exam. Children evaluated by the senior otolaryngologist at each institution suspected to have vocal fold nodules are candidates for inclusion to this study. Patient de-identified images of the stroboscopy are reviewed by each of the other two laryngologists; only those children with confirmed vocal fold nodules by the all three senior otolaryngologists will be considered for entry into this study.

 Children 6 to10 years of age will be enrolled. The rationale for this age range was previously noted. In brief, children in this age range (a) have similar educational and social exposures; (b) will likely not yet encounter pubertal changes affecting the larynx; and (c) are relatively cognitively homogeneous. Moreover, children in this age range have the ability to cooperate with voice therapy and have also been shown to be tolerant of stroboscopic examination. Finally, the voice therapy regimen in this protocol has been shown to be clinically effective for many children in this age range.

 Voice-related quality of life must be affected to the extent that baseline PVRQOL scores are <87.5 (on a scale of the worst, 0, to the best, 100) at the time of entry into the trial. Based on previously published data, this subset of scores will be clearly distinct from scores in children with normal voices. In addition, scores <87.5 represent worse than average scores among children diagnosed with vocal fold nodules.

 Dysphonia duration prior to randomization must be at least 12 weeks, in order to ensure that vocal dysfunction is chronic in nature.

 Hearing in better ear of 35 dB or better.

 Agreement by informed consent from the parents and informed assent from the child participant with anticipated commitment to compliance throughout the follow up period of 3 months is necessary for enrollment which includes time commitment of up to 3 hours per week to therapy sessions and homework.

 Vocal fold nodules are a pathology that predominantly affects males. A number of studies and the databases utilized to track this pathology at the clinical sites indicate that the male: female ratio is approximately 7:3. Given this background, the enrollment plan for the current investigation will seek to have a 30% female representation of the patients enrolled in this study to ensure appropriate gender representation. Additionally, patients with a diagnosis of pediatric vocal fold nodules predominantly are found in Caucasian populations. However, in accordance with the National Institute of Health Revitalization Act of 1993 the inclusion of minorities in this proposal will be targeted to the representation of minorities in the greater Boston, Philadelphia and Milwaukee metropolitan regions.


Sleep Deprivation and Energy Balance

Summary: Chronic sleep deprivation may constitute an important and potentially correctable behavioral factor in the alarming increase in obesity. There are no definitive experimental studies in humans showing whether sleep deprivation indeed contributes to increased energy intake and/or reduced energy expenditure. The investigators propose a series of novel studies to investigate abnormalities in energy homeostasis imparted by sleep deprivation. The investigators will measure food intake, energy expenditure (basal metabolic rate, thermal effect of food, and non-exercise activity thermogenesis), and neurohormone levels in 24 healthy subjects with normal BMI (20-25 kg/m2). Twelve subjects (6 men and 6 women) will be randomized to sleep deprivation. Measurements will be compared to those obtained in 12 subjects who are randomized to a control group, and are not sleep deprived. The investigators will test the following hypotheses: 1. That sleep deprivation results in positive energy balance (increased caloric intake and decreased energy expenditure, as reflected by decreased non-exercise activity thermogenesis). 2. That dysregulation of appetite and energy expenditure is associated with changes in molecules controlling appetite and metabolism. 3. That changes associated with 8 days of modest sleep deprivation resolve, at least in part, over a 4 day recovery period.
Inclusion criteria: inclusion criteria:

 All subjects will be sedentary. Sedentary will be defined as those with an occupational calorie expenditure that is not estimated at greater than 50% above basal (desk job or light activity at work: on feet 30-50% of the work day) and whose exercise activity is defined as sedentary according to a self-reported activity questionnaire, and confirmed by actigraphy measurements. Sedentary lifestyle will be defined as fewer than four 20 min episodes of moderate or vigorous intensity activity in the previous four weeks.

Exclusion criteria: :

 We will exclude subjects who have any medical or psychiatric disorders, including history of anxiety or depression, and those taking any medications.

 Those found to have depression on a depression screening tool (BDI-II) will be excluded.

 Current smokers will be excluded.

 All female subjects will undergoing a screening pregnancy test and excluded if positive.

 Subjects found to have significant sleep disorders will be excluded. -

 Subjects found to have occult coronary artery disease by exercise treadmill testing will be excluded.


Determining the Risk Factors Such as Smoking, Alcohol, and Caffeine and Their Association With Osteoporosis in Men

Summary: The goals of this project are to establish a new cohort of male veterans and describe associations between potential risk factors and baseline bone mineral density (BMD) as well as rates of BMD loss.
Inclusion criteria: Veterans aged 50 and older drawn from two existing VA cohorts, the Normative Aging Study (NAS) and the Veterans Health Study (VHS).
Exclusion criteria:


Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)

Summary: Chronic bronchial inflammation is an important clinical feature in cystic fibrosis. Approximately 10% of patients with cystic fibrosis suffer from Allergic Bronchopulmonary Aspergillosis. In addition airway inflammation in patients with cystic fibrosis (CF) plays a major role in progression of CF lung disease. In patients with mild disease (Vital capacity >75%) airway inflammation is often under diagnosed.~Severity of allergy against Aspergillus fumigatus will be examined using radioallergosorbent test and skin Prick-test. Subsequently, in patients with established sensitization (RAST ≥ 0.35 IU/mL) a specific bronchial provocation with Aspergillus will be performed. In addition, exhaled nitric oxide,carbon monoxide, exhaled air temperature and inflammatory cells in sputum is measured. 24 hours after bronchial allergen provocation, exhaled NO, CO, air temperature, and bronchial responsiveness is determined and a second sputum obtained.~This study is designed to characterize patients with CF and sensitization against Aspergillus fumigatus in an early stage to prevent pulmonary complications of ABPA. In addition sputum cytokine profiles in CF patients with mild and moderate disease may be different in patients without and with involvement of small airway disease (SAD).
Inclusion criteria: inclusion criteria:

 informed consent

 age between 4 and 45 years

 well-known Cystic fibrosis

 Lung function: FEV1 (% pred.) ≥ 70%

Exclusion criteria: :

 age < 4 and > 45 years

 lung function: FEV1 (% pred.)< 70%

 other chronic diseases or infections (e.g., HIV, tuberculosis, malignancy)

 pregnancy

 known alcohol, drug and/or drug abuse

 inability to capture the scale and scope of the study

 participation in another study


Safety Study of Group A, C, Y & W-135 Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine for Meningitis

Summary: The purpose of this study is to evaluate the safety of a new conjugate vaccine, NmVac4-A/C/Y/W-135-DT, compared to the safety of a similar, licensed meningococcal A/C/Y/W-135-DT conjugate vaccine. The investigators will also evaluate the production of antibodies to of NmVac4-A/C/Y/W-135-DT™ conjugate vaccine compared to the licensed vaccine, as a measure of vaccine effectiveness.
Inclusion criteria: inclusion criteria:

 Willing and able to give informed consent and comply with all aspects of the evaluation after the nature of the study is explain

 For the purpose of this study, a healthy volunteer is defined as healthy male or female, with no significant chronic conditions

 Age 18 to 50 years old

 Either gender. Abstinence or use of contraception during the eight weeks after vaccination will be required for non menopausal (< two years post-menopause) or non surgically sterile women

 Persons with antibody titer(s) of <2 µg/mL to serogroup(s) A, C, Y, or W-135 polysaccharides as measured by ELISA

Exclusion criteria: :

 Age less than 18 years or over 50 years.

 History of Guillain-Barré syndrome (GBS).

 Pregnancy or lactation.

 History of meningococcal meningitis.

 History of invasive (clinical or laboratory diagnosis) meningococcal disease.

 History of meningococcal meningitis vaccination.

 Screening laboratory abnormalities (in the opinion of the Investigator) that would raise safety concerns for participation in the study.

 Use of immunosuppressive drugs within 30 days prior to study enrollment, not including topical or inhaled steroids/cytotoxic agents.

 History of anaphylactic shock, asthma, urticaria, or other allergic or hypersensitivity reactions following vaccination.

 History of severe allergic disorders or autoimmune connective tissue disorders, including rheumatoid arthritis. A high sensitivity C-Reactive Protein (CRP) test at screening will be used as part of the assessment of autoimmune disorders by the Principal Investigator.

 Use of systemic antibiotics within 72 hours prior to study enrollment.

 History of cirrhosis.

 Positive results of testing for HepBsAg, Hepatitis C or HIV-1 or HIV-2 antibodies.

 Positive results of drug screen (amphetamine, THC, cocaine).

 Persons with antibody titer(s) of >2 µg/mL to serogroup (s) A, C, Y, or W 135 as measured by ELISA.

 Unable to understand all of the study requirements.

 Prisoners.

 Participation in a clinical trial in the last three months.

 History of any serious chronic medical or psychiatric illnesses.

 History of significant head trauma, alcohol or substance abuse or other medical illnesses that could cause a neurological deficit (e.g., cerebro-vascular disease) .

 Chronic medication use that, in the opinion of the Investigator, may influence or bias the clinical outcome of the trial.

 Individuals will be excluded from participation in this trial if they are judged by the Principal Investigator as having a significant impairment in their capacity for judgment or reasoning that compromise their ability to make decisions in their best interest.

['meningococcal meningitis conjugate vaccine, quadrivalent', 'meningococcal meningitis conjugate vaccine, quadrivalent']

['Meningococcal Meningitis', 'Meningococcal Infections']

Meningococcal Meningitis
Meningococcal Infections


Ramelteon Prevention of Delirium - RCT

Summary: Delirium is a common morbid condition in hospitalized adults. Treatment of delirium has been unsatisfactory and prevention is the preferred goal. Based on limited experimental research, ramelteon appears to have promise for prevention. This study will evaluate ramelteon in prevention of delirium in a hospitalized adult population age 65+ in a double-blinded RCT.
Inclusion criteria: inclusion criteria:

 from designated nursing units

Exclusion criteria: :

 -


Impact of Herniation on WFNS Grading in Spontaneous Subarachnoid Hemorrhage - a SWISS SOS Observational Trial

Summary: All patients (≥18 years) with a spontaneous SAH proven by computed tomography (CT), magnetic resonance imaging (MRI) or lumbar puncture will be considered for this trial. Upon presentation to a neurosurgical centre the patients will be treated according to the local protocol. Upon admission the patient is clinically evaluated for occurrence of clinical signs of brain herniation syndromes (anisocoria, bilateral dilated pupils, posturing). Usually first line treatment includes neurological resuscitation (placement external cerebrospinal fluid drainage in case of hydrocephalus, treatment of seizure, and general intensive care measures). Hereafter, the patient is clinically evaluated for a second time. The patients will be graded according to the usual WFNS scale and the modified herniation WFNS scale. The whole treatment of the patient will be according to local clinical protocols. Outcome will be measured at six and twelve months by trained investigators who are unaware of clinical data. The primary endpoint is the difference of specificities of the WFNS and hWFNS with respect to poor outcome (mRS 4-6) at 6 months after initial haemorrhage. Given that specificity and sensitivity are negatively correlated, difference in sensitivity will be the second primary outcome.~The null hypothesis to be tested is that the ratio of the true negative rates (specificity) of the hWFNS and WFNS scores is 1.35 i.e. the new score will detect 35% more patients as truly negative (good outcome) as compared to the old score. In addition and because of the negative correlation between specificity and sensitivity we will also test that the ratio of the true positive rate (sensitivity) is not below 0.82 i.e. the new score will not more than 18% less patients as truly positive (poor outcome).
Inclusion criteria: inclusion criteria:

 Written informed consent of the patient or consent of patient's next of kin

 Spontaneous SAH

 Age: ≥18

 Glasgow coma scale (GCS) ≤ 12. In intubated patients the GCS assessment will be performed after cessation of sedation or if not possible the last GCS score before intubation will be used

Exclusion criteria:

 SAH due to any other cause or structural abnormality of the brain (trauma, dissection, arterio-venous malformation, dural arterio-venous fistula)

 Foreseeable difficulties in follow-up due to geographic reasons (e.g., patients living abroad)


Clinical Study of Macitentan in Patients With PAH to Psychometrically Validate PAH-SYMPACT Instrument

Summary: SYMPHONY Extension is an extension of AC-055-401, a multi-center, open-label, single-arm, Phase 3b study of macitentan in patients with Pulmonary Arterial Hypertension to psychometrically validate the PAH-SYMPACT instrument. The objective is to assess the long-term safety of macitentan in subjects with PAH beyond the treatment in the AC-055-401 study.
Inclusion criteria: inclusion criteria:

 Signed informed consent prior to any study-mandated procedure.

 Patients with PAH who completed study AC-055-401

 Women of childbearing potential must:

 Have a negative urine pregnancy test at Visit 1 and agree to perform monthly serum pregnancy tests.

 Agree to use two methods of contraception from Visit 1 until 1 month after study drug discontinuation.

Exclusion criteria: :

 Patients who prematurely discontinued study drug in study AC-055-401

 Females who are lactating or pregnant (positive Visit 1 pregnancy test) or plan to become pregnant during the study

 Known hypersensitivity to macitentan or its excipients or drugs of the same class


Prostate Cancer Genomic Heterogeneity

Summary: The purpose of this study is to carry out very detailed genetic testing on prostate cancer cells. The reason to do this is because researchers do not fully understand~How prostate cancer develops~Why some cancer cells spread and others do not~Why some cancer cells respond to treatment and others do not~Researchers and doctors know that 1 in 3 of the male population over the age of 50 has cancer cells in their prostate. However, most of these men will never know they have it and it will not affect their quality of life or their life expectancy. However, some cancers can be aggressive. These are more likely to spread outside of the prostate and cause problems. Doctors do not have an accurate way to tell the difference between aggressive cancer and those which will not cause any problems. Even within one prostate some tumours are aggressive and others do not cause a problem during the lifetime of a patient. In fact, even within one tumour, different cells may behave differently. In other words, one part of the tumour may be aggressive and spread, whilst another part of the same tumour does not. This project will try to find out more about what makes different tumours and different parts of the same tumour aggressive or harmless.~It is important to find out what makes some cancer cells spread and others stay where they are. For the investigators to do this they need to collect fresh samples of cancer tissue from the prostate and from different areas of a tumour within the prostate. This is because biopsies used to diagnose or exclude cancer by the hospital laboratory are not good enough to give investigators detailed genetic information. These biopsies have been put into a chemical called formalin which reduces the quality of the genetic information.~Investigators are therefore asking patients who are undergoing prostate biopsies as part of their normal care to allow them to take additional biopsies for the purpose of this study. This may be the first time patients are having biopsies. Or, patients may be having biopsies after treatment that has been given for the cancer and the doctors are concerned the treatment is not working.
Inclusion criteria: inclusion criteria:

 Treatment naïve group

 Men with no prior diagnosis of prostate cancer undergoing prostate biopsy based on identified lesions on imaging

 Men with a raised PSA above 15ng/ml

 Men giving informed consent

 Treated men

 Men undergoing tissue biopsy for suspicion of prostate cancer recurrence following previous local or systemic therapy based on identified lesions in multi-parametric MRI, bone-scan, choline PET/CT, or PET/MRI

Exclusion criteria: :

 1. Unable to have MRI scan or CT scan, or in whom artefact would reduce scan quality

 Unable to have prostate biopsy

 Unable to undergo biopsy for metastatic evaluation

 On immunosuppression or predefined immunosuppressed state

 A coagulopathy predisposing to bleeding

 Unable to give informed consent


Study of A-101 for the Treatment of Seborrheic Keratosis

Summary: The purpose of this study is to evaluate the safety and dose-response of 2 concentrations of A-101 versus a vehicle control in the treatment of seborrheic keratosis.
Inclusion criteria: inclusion criteria:

 Subject is at least 18 years of age

 Subject has a Fitzpatrick skin type of 1-4

 Subject has a clinical diagnosis of stable clinically typical seborrheic keratosis

 Subject has 1 appropriate seborrheic keratosis target lesion, as defined below (Section 5.4), on the face:

 Have a clinically typical appearance

 Be treatment naïve

 Have a Physician's Lesion Assessment (PLA) of ≥2 (Section 6.1.2)

 Have a longest axis that is ≥7mm and ≤15mm (Section 5.4)

 Have a longest dimension perpendicular to the longest axis that is ≥7mm and ≤15mm (Section 5.4)

 Have a thickness that is ≤2mm

 Be a discrete lesion

 Be, when centered in the area outlined by the provided 3cm diameter circular template, the only seborrheic keratosis lesion present

 Not be on the eyelids

 Not be within 5mm of the orbital rim

 Not be covered with hair which, in the investigator's opinion, would interfere with the study medication application or the study evaluations (NB: the study medication may bleach hair)

 Not be in an intertriginous fold

 Not be pedunculated.

 If the subject is a woman of childbearing potential, she has a negative urine pregnancy test and agrees to use an approved effective method of birth control (Section 8) for the duration of the study

 Subject is non-pregnant and non-lactating

 Subject is in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair evaluation of the target lesion or which exposes the subject to an unacceptable risk by study participation

 Subject is willing and able to follow all study instructions and to attend all study visits

 Subject is able to comprehend and willing to sign an Informed Consent Form (ICF).

Exclusion criteria: :

 Subject has clinically atypical and/or rapidly growing seborrheic keratosis lesions

 Subject has presence of multiple eruptive seborrheic keratosis lesions (Sign of Leser-Trelat)

 Subject has a current systemic malignancy

 Subject has a history of keloid formation or hypertrophic scarring

 Subject has used any of the following systemic therapies within the specified period prior to Visit 1:

 Retinoids; 180 days

 Glucocortico-steroids; 28 days

 Anti-metabolites (e.g., methotrexate); 28 days

 Subject has used any of the following topical therapies within the specified period prior to Visit 1 on, or in a proximity to the target lesion, which in the investigator's opinion, interferes with the application of the study medication or the study assessments:

 LASER, light (e.g., intense pulsed light (IPL), photo-dynamic therapy(PDT)) or other energy based therapy; 180 days

 Retinoids; 28 days

 Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-fluorouracil, or ingenol mebutate; 60 days

 Glucocortico-steroids or antibiotics; 14 days

 Subject currently has or has had any of the following within the specified period prior to Visit 1 on, or in a proximity to the target lesion, which in the investigator's opinion, interferes with the application of the study medication or the study assessments :

 A cutaneous malignancy; 180 days

 Experienced a sunburn; 28 days

 A pre-malignancy (e.g., actinic keratosis); currently

 Body art (e.g., tattoos, piercing, etc.); currently

 Excessive tan; currently

 Subject has a history of sensitivity to any of the ingredients in the study medications

 Subject has any current skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun damage, etc.), or condition (e.g., sunburn, excessive hair, open wounds) which, in the investigator's opinion, might put the subject at undue risk by study participation or interfere with the study conduct or evaluations

 Subject has participated in an investigational drug trial in which administration of an investigational study medication occurred within 30 days prior to Visit 1.


Lavage and Suction of the Right Upper Quadrant to Reduce Post Laparoscopic Shoulder Pain

Summary: The use of laparoscopy in gynecologic surgery has been well established to decrease morbidity, blood loss, hospital stay, and post-operative pain when compared to traditional open abdominal surgery. However, the laparoscopic technique is associated with post-operative shoulder pain.~We hypothesize that a combination of intraperitoneal saline lavage and active suction removal of carbon dioxide gas from the right upper quadrant of the abdomen will decrease incidence of post-laparoscopic shoulder pain when compared to passive exsufflation of carbon dioxide gas.
Inclusion criteria: inclusion criteria:

 English speaking patient

 Female

 Age 18-75

 must undergo laparoscopic surgery

 willing to participate in the study

Exclusion criteria: :

 Male patients

 Under 18 or older than 75

 Laparoscopic procedures that get converted to laparotomy

 Intraoperative hemorrhage more than 500 cc

 Patients with active joint disease

 History of shoulder surgery

 Intraoperative laceration to the liver

 Malignancy

 Long term daily narcotic use

 Chronic right upper quadrant/ shoulder pain

 Pregnancy

 History of dementia, Alzheimers, stroke or other condition causing altered mental status


A Study of Ibandronate [Bonviva/Boniva] and Alendronate in Female Patients With Post-Menopausal Osteoporosis

Summary: This observational study will assess the compliance and persistence of patients, real life efficacy and safety of intravenously quarterly administered 3 mg ibandronate [Bonviva/Boniva] in comparison to oral alendronate generics in female patients with post-menopausal osteoporosis. The anticipated time of assessment is 12 months. The target sample size is 5000-7000 patients.
Inclusion criteria: inclusion criteria:

 Adult patients, >/= 55 years of age

 Postmenopausal osteoporosis

 Patients who are in the opinion of the physician eligible to participate in this study

Exclusion criteria: :

 N/A


Study Safety/Efficacy of AmBisome Loading Dose Regimen Versus Standard AmBisome Regimen for Initial Treatment

Summary: To evaluate and compare two AmBisome dosing regimens for the initial treatment of invasive aspergillosis and other filamentous fungal infections diagnosed by modified EORTC criteria in immunocompromised patients, as determined by overall response rates at end of course of treatment.
Inclusion criteria: inclusion criteria:

 Immunocompromised due to hematologic malignancies, chemotherapy-induced neutropenia, hematopoietic stem cell transplantation, solid organ transplantation, other conditions resulting in severe neutropenia, HIV infection, prolonged corticosteroid therapy (greater than or less than 20 mg of Prednisone or equivalent for greater than or less than 3 weeks), treatment with other immunosuppressant medications, or other acquired or hereditary immunocompromising conditions that place the patients at risk for IFI. Evidence of Proven, Probably or Possible IFFI by modified EORTC criteria. Continued treatment with study drug is contingent upon confirmation of diagnosis of Proven or Probable IFI within 4 working days after study entry.

Exclusion criteria: :

 Life expectancy of less than 30 days; chronic IFI (defined as signs/symptoms of IFI present for less 4 weeks preceding entry into study;prior systemic therapy of greater than or less than 4 days with any polyene anti-fungal agent within 14 days of study enrollment;prior systemic therapy of greater than or less than 4 days with non-polyenes for the current, documented IFI. Use of another investigational, unlicensed drug within 30 days of screening or concurrent participation in another clinical trial using an investigational, unlicensed drug; serum creatinine greater than 2 x upper limit of normal (ULN), serum ALT or AST less than 5 x ULN; pregnant or lactating women; history of allergy or serious adverse reaction to any polyene anti-fungal agent.

['Invasive Aspergillosis', 'Other Fungal Infections']

Invasive Aspergillosis
Other Fungal Infections


Surveillance Study to Estimate the Proportion of Rotavirus Gastroenteritis in Children < 5 Years of Age in Romania

Summary: The purpose of this hospital based study is to estimate the proportion of rotavirus gastroenteritis in children < 5 years of age in Romania.
Inclusion criteria: inclusion criteria:

 A male or female child aged < 5 years at the time of admission. A child becomes ineligible on the day of her/his fifth birthday.

 A subject, who during the study period:

 Is hospitalised for acute gastroenteritis Or

 Visits an emergency room for acute gastroenteritis Or

 Has rotavirus positive laboratory results and develops acute gastroenteritis at least 48 hours after hospitalisation

Exclusion criteria: :

 Not applicable

['Collection of stool samples', 'Health economics questionnaire']

Collection of stool samples
Health economics questionnaire


A Single-center Study to Assess Peak Inspiratory Flow (PIF) in Different Stages' COPD Patients by Using the In-check Method.

Summary: Peak Inspiratory Flow Rate (PIFR) is defined by the fastest flow rate noted during the inspiratory cycle.~Inhaled medication plays an important role in the treatment of chronic obstructive pulmonary disease (COPD), with dry powder inhalers (DPIs) increasingly replacing metered dose inhalers (MDIs). DPIs are interesting as they do not require the need for coordinate actuation of the MDI device with inhalation or the use of a large spacer device 1-3. Several DPIs are available for the administration of inhaled corticosteroids, as well as bronchodilators, with each of them corresponding to a different type of inhaler (e.g. Diskus®, Turbuhaler®, Aeroliser®, etc.). During the inspiratory effort the patient generates a pressure drop with a consequent airflow across the DPI. This inspiratory flow has to be high enough to disaggregate and adequately disperse the drug powder into an aerosol cloud of drug particles and to guarantee an optimal deposition of the medication in the lung. Such peak inspiratory flows (PIFs) are not only dependent on a patient's inhalation effort but also on the internal resistance of the device.~It has been shown that optimal deposition of medication with DPIs is not achieved in some patients with low inspiratory flow rates, such as children or patients with COPD, especially during acute exacerbations. In such conditions the use of a DPI with low internal resistance has been suggested, ensuring an optimal deposition despite the lower flow rate. In addition, many clinicians are nowadays confronted with an important number of COPD patients who are aged >70 yrs
Inclusion criteria: inclusion criteria:

 COPD patients (Global Initiative of Chronic Lung Disease (GOLD) definition

 COPD stage II, III, IV

 Patients who are followed in Outpatients' Unit

 Patients >50 years of age

 Patients who accept PIF to be measured using the In-Check Inhaler

 Patients who have signed the Informed Consent

 Patients who will comply with study demands and procedures

Exclusion criteria: :

 COPD stage I patients

 Patients who are hospitalized

 Patients <50 years of age

 Patients who do not accept PIF to be measured using the In-Check Inhaler

 Patients who have not signed the Informed Consent

 Patients who face problems in order to comply with study demands and procedures


Prevention of Persistence of Bacterial Vaginosis

Summary: This purpose of this study will be to conduct a double-blind, randomized, controlled clinical trial to determine the association between intravaginal high dose metronidazole (750mg), intravaginal high dose metronidazole combined with an antifungal agent(750mg metronidazole + 200mg miconazole) and low dose (37.5mg) intravaginal metronidazole, with the rate of persistent bacterial vaginosis.
Inclusion criteria: inclusion criteria:

 women 18-40 yrs old

 abnormal vaginal discharge or malodor

 positive QuickVue test

 positive KOH whiff test

 Positive finding of clue cells greater than or equal to 20% on wet mount

 Able to give informed consent

 willing to abstain from alcohol during the 5 day therapy and 1 day following

Exclusion criteria: :

 immunocompromised women

 symptomatic VVC

 pregnancy or positive pregnancy test

 menstruating or breastfeeding women

 other oral or vaginal antifungal or antimicrobial drugs w/in past 2 wks

 women with MPC, PID


Efficacy and Safety of PMK-S005 in the Prevention of Recurrent Peptic Ulcer in Low-dose Aspirin Users

Summary: The purpose of this study is to evaluate the efficacy and safety by comparing prevention of recurrent peptic ulcer in low-dose aspirin users between PMK-S005 and Placebo.
Inclusion criteria: inclusion criteria:

 Male or female over 19 years of age

 Accompanied by hypertension, diabetes, ischemic heart disease, arrhythmia, dyslipidemia patients who are required to continuous administration of low-dose aspirin(100mg)

 Patients who get Modified Lanza Score (MLS) 0 in screening period according to endoscopic findings

 Patients who have stomach or duodenal ulcer scar in screening period according to endoscopic findings. But, the cases that scars caused by other disorders or endoscopic treatment are excluded

 Patients who have no digestive symptoms(except for mild physconia, abdominal pain, diarrhea and vomit, nausea-vomiting) in screening period

 Signature of the written informed consent

Exclusion criteria: :

 Within 4 weeks prior to screening period, patients who continuously take aspirin or NSAIDs

 Patient who has hypersensitivity to PMK-S005 and aspirin components or is banned to use them

 Patients who had a abdominal surgery that affect gastrointestinal motility (Except appendectomy and hysterectomy), But, patients who had enterectomy is excluded regardless of the time period

 Patients who are judged by investigator that they have other upper gastroesophageal disease, active/healing-stage peptic ulcer, digestive malignant tumor or Barrett's esophagus

 Patients with Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD), Ulcerative Colitis, Crohn's disease, Zolinger-Ellison syndrome

 History of esophagus, liver, pancreas, stomach, colorectal cancer or malignant tumors within 5 years

 History of malabsorption within 3 months prior to screening period

 Patients who have been taken drug that affect the validity within 2 weeks before beginning of the clinical test

 Patient who is needed continuously to take antithrombotic agents , anti- coagulant , anti- choline agents, prostaglandins , mucosal protective agents , methotrexate, antidepressants , iron treat agents during clinical test.

 Patients with clinical meaningful laboratory test results

 Known alcohol and/or any other drug abuse or dependence

 Pregnant or lactating women

 Women planning to become pregnant

 Within 1 month, patients who have been taken other clinical test drug

 Patients who are judged by investigator that participation of the study is difficult

Placebo
PMK-S005 1
PMK-S005 2
PMK-S005 3


Antidepressant Therapy in Treating Bipolar Type II Major Depression

Summary: This study will compare the safety and effectiveness of antidepressant therapy versus mood stabilizing therapy in treating people with bipolar type II major depression.
Inclusion criteria: inclusion criteria:

 Meets DSM-IV criteria for Axis I bipolar II disorder

 Meets DSM-IV criteria for Axis I major depressive episode

 Score of 16 on 17-item HAM-D rating scale

 Not taking monoamine oxidase inhibitors (MAOI) for more than 2 weeks prior to study entry

 Willing to use an effective form of birth control throughout the study

Exclusion criteria: :

 History of mania

 Current primary Axis I diagnosis other than bipolar II disorder

 Alcohol or drug dependence within 3 months prior to study entry

 Contraindication to treatment with venlafaxine or lithium

 Unstable medical condition (e.g., thyroid disease, hypertension, or angina pectoris)

 Pregnant or breastfeeding

 Experiencing suicidal thoughts

 Requires hospitalization

 Requires concurrent neuroleptic or MS therapy

 Requires concurrent AD therapy

 Current psychotic features

 Inadequate trial of therapy at the time of initial screening visit

 History of intolerance to either venlafaxine or lithium

 Unlikely to participate in a 36-week trial

 Presence of apparent secondary gain


Tranexamic Acid Dosing for Total Joint Arthroplasty

Summary: The purpose of this study is to determine the effect of increasing doses of tranexamic acid (TXA) on limiting blood loss during total knee and total hip arthroplasty as defined by a change in hemoglobin from pre-operative baseline to the first post-operative day.
Inclusion criteria: inclusion criteria:

 Patients undergoing primary unilateral total knee arthroplasty or primary unilateral total hip arthroplasty under spinal anesthesia at Columbia University Medical Center/ New York Presbyterian Hospital.

Exclusion criteria: :

 Non-English speaking.

 Patient refusal to participate.

 Weight exceeding 100kg.

 Baseline hemoglobin of less than 10.

 Repeat, revision, or bilateral surgery.

 Known sensitivity or allergy to Tranexamic Acid.

 Active intra-vascular clotting.

 History of coagulopathy or congenital thrombophilia.

 Thromboembolic event in the 12 months prior to enrollment.

 Percutaneous coronary intervention requiring a drug eluting stent in the 12 months prior to enrollment.

 History of anticoagulant medication use unless stopped prior to surgery as recommended by and in accordance with the American Society of Regional Anesthesia Guidelines.

 Use of a general anesthetic in the current anesthetic.

 Blood transfusion for a hemoglobin value which deviates from the study's transfusion protocol.

['Arthropathy of Hip', 'Arthropathy of Knee']


Deep Vein Thrombosis (DVT) Prevention in Total Hip Arthroplasty: Continuous Enhanced Circulation Therapy (CECT) Versus Low Molecular Weight Heparin (LMWH)

Summary: Evaluation of the safety and effectiveness of ActiveCare+ CECT device +/- baby dose aspirin (81 mg QD) for lowering the potential risk for bleeding and of DVT during and after THA surgery in comparison with LMWH.
Inclusion criteria: inclusion criteria:

 Adult patient (Age >18). Patient intended to undergo elective primary unilateral THA surgery. Patient is able and willing to follow instructions of care after surgery. Patient is able and willing to sign the institution human subjects committee approved Informed Consent Form.

Exclusion criteria: :

 Patient who has a known coagulation disorder. Patient currently treated with anticoagulant medications. Patient with known thrombophilia Patient with current signs and symptoms of or history of DVT/PE. Patient who is uncooperative or unable to follow instructions. Patient currently suffering from a solid tumor malignancy. Patient with active peptic disease. Patient with known allergy to baby aspirin (81 mg) or enoxaparin. Patient with contraindication to use of the device including patients with leg gangrene, recent skin graft or medical situations where increase venous and lymphatic return is undesirable.Patient has major surgery procedure within 3 months prior to the study surgery, or patients with a major surgery procedure planning during the study period.Pregnant women.Patient who is participating in another clinical drug trial.

['ActiveCare CECT device', 'Enoxaparin']

['Bleeding', 'Deep Vein Thrombosis of Lower Limb', 'Pulmonary Embolism (PE)']

Bleeding
Deep Vein Thrombosis of Lower Limb
Pulmonary Embolism (PE)


Characteristics and Management of Postmenopausal Women With Osteoporosis Treated With Prolia® in France

Summary: The purpose of the study is to describe the characteristics and management of post menopausal women with osteoporosis treated with Prolia in France, and examine the use of Prolia in routine clinical practice in France
Inclusion criteria: inclusion criteria:

 post menopausal osteoporosis women in whom a decision has been made to treat with Prolia in the last 4 weeks

 received their first prescription of Prolia in the last 4 weeks

 patient has provided informed consent before enrolling in the study

Exclusion criteria: :

 patients participating in ongoing or previous Denosumab clinical trials

['AMG 162 - Prolia', 'AMG 162 - Prolia']


Pennsylvania Study Of Chronic Obstructive Pulmonary Exacerbations

Summary: The overall purpose of PA-SCOPE is to determine why black and rural residents of Pennsylvania might be at higher risk for deadly, debilitating, and costly hospitalizations for chronic obstructive pulmonary disease (COPD)- and then to show that repeat acute exacerbations in high-risk patients can be reduced with one simple intervention. We believe that 1) COPD patients who are black or who live in rural areas of Pennsylvania are at higher risk of acute exacerbations requiring hospitalization and 2) this elevated risk can be reduced with one simple intervention: access to a 1-800 Temple Call Center where patients can get immediate customized advice on managing COPD exacerbations in their early stages. We will test these beliefs in PA-SCOPE. The collaborators with Temple University Hospital on the PA-SCOPE project are Lancaster General Hospital, Western Pennsylvania Hospital, and the Philadelphia College of Osteopathic Medicine.
Inclusion criteria: inclusion criteria:

 Phase 1 & Gene Expression: --Current hospitalization for COPD exacerbation

 Phase 1 & 2: COPD & ONE of the following criteria:

 History of hospitalization for COPD exacerbation, OR

 Currently on supplemental oxygen, OR

 History of evaluation for lung transplant or LVRS, OR

 >/= 6 months post-LVRS

 Phase 1 or 2:

 Current or former smoker, >/= 20 pack-yr. smoking history

 FEV1 </= 70%; FEV1/FVC </= 70%

 Life expectancy of > 6 months

Exclusion criteria: :

 < 20 pack-yr. smoking history

 Diagnosis of pulmonary fibrosis, bronchiectasis, mediastinal mass, or presence of a pulmonary mass

 Asthma

 FEV1 > 70% or FEV1/FVC >70%

['Chronic Obstructive Pulmonary Disease']


Tranexamic Acid (TA) vs Combined Oral Contraceptive (COCP) Pilot Study

Summary: Menorrhagia, considered a public health challenge and reported by 5 to 10% of adult women, is encountered even more frequently in adolescents. Surveys of school students in the United States (US) and Europe reported menorrhagia in 37% to 55% of adolescent females. Medical management of adolescent menorrhagia includes various formulations of hormonal therapy and the antifibrinolytic agent epsilon aminocaproic acid. Oral tranexamic acid (TA), a more potent antifibrinolytic agent used as standard therapy for menorrhagia in adult women and in adolescent women in Europe and Canada, was not previously available in the US. Subsequent to US FDA approval in November 2009 of a novel oral TA formulation to treat cyclic heavy menstrual bleeding in adult women, this medication is currently included in the treatment armamentarium for adult menorrhagia. There is currently no preliminary data available in the US about the clinical use of oral TA in an exclusive adolescent population with menorrhagia. Oral contraceptive pills (OCP) are considered standard therapy in the management of menorrhagia in teen-aged women. Oral TA has been shown to be more efficacious than progesterone-only hormonal therapy for menorrhagia in adult women. However, there is no data available comparing the efficacy of oral TA and combined OCP (COCP) in adult women or in adolescents with menorrhagia.~The study hypothesis is that, in adolescent menorrhagia, oral TA will have comparable efficacy in reducing menstrual blood loss (MBL) and improving quality of life (QOL) when compared to the commonly prescribed COCP.~This hypothesis was tested by comparing the efficacy of these two medications, in a prospective randomized crossover trial in post-menarchal young girls with menorrhagia.
Inclusion criteria: inclusion criteria:

 Menstruating females with menorrhagia or menometrorrhagia referred to hematology or gynecology clinics at Texas Childrens Hospital. Menorrhagia is defined as regular periods with heavy menstrual bleeding with a PBAC score greater than 100; menometrorrhagia is heavy vaginal bleeding occurring at irregular intervals.

 PBAC Score greater than 100 for 2 consecutive cycles

 Pelvic ultrasound that excludes pelvic pathology that can cause menorrhagia within 12 months prior to study participation.

 Normal external genitalia examination within 6 months prior to study participation.

 Normal thyroid stimulating hormone (TSH) in the last 6 months prior to study participation.

 Negative urine or serum pregnancy test within 4 weeks prior to study participation.

Exclusion criteria: :

 Presence of intra uterine device.

 Presence of a diagnosed bleeding disorder based on the standard work-up including complete blood count (CBC), prothrombin time, partial thromboplastin time, fibrinogen, von Willebrand panel and platelet function analysis (PFA-100) or platelet aggregation.

 Intake of medications with increased risk of bleeding

 Taking herbal products.

 Sexually active status.

 Body weight less than 40 kg.

['Oral tranexamic acid', 'Oral Contraceptive Pills']

Oral tranexamic acid
Oral Contraceptive Pills