Ondansetron for Pediatric Mild Traumatic Brain Injury

Summary: Background: Most patients suffering from mild Traumatic Brain Injury (mTBI) present persistent symptoms at one week post injury. A systematic review showed a paucity of studies for short term outcomes following mTBI. Among potential treatments for mTBI, ondansetron has shown promising results based on clinical experience and a single retrospective study. Objectives: The primary objective of this pilot study is to determine the feasibility of a randomized controlled trial evaluating the effect of ondansetron to decrease post concussion symptoms at one week following mTBI in children. More specifically, this pilot study will evaluate the proportion of participants who complete assessment at one week following intervention. Method: This will be a randomized, double blinded, controlled trial performed among children aged between 8 and 17 years old who sustained a mTBI in the previous 24 hours. Participants visiting the emergency department will be randomized to receive one dose of either ondansetron or placebo. The primary outcome of interest is defined as an increase from pre-concussion baseline of at least 3 symptoms from the Post Concussion Symptom Inventory (PCSI) one week following trauma. Secondary outcomes will include time to full recovery, mean PCSI score, and outcomes at one month following head trauma. The primary analysis will compare the proportion of participants with persistence of symptoms at one week in both groups. The full study sample size was calculated to have 90% power to detect a decrease in the proportion of persistence of symptoms from 50% to 30% with an alpha value of 0.05. Approximately 126 patients will therefore be recruited in each arm. The investigators plan to recruit 30 participants (10% of the final population) for the pilot study. Expected results: This pilot study should confirm the feasibility of the randomized controlled trial by showing that 90% of the recruited participants provide data on the primary outcome at one week following intervention. On the long term, the investigator expect that ondansetron will decrease the proportion of patients sustaining persistent symptoms of concussion from 50% to lower than 30%.
Inclusion criteria: inclusion criteria:

 Children aged between 8 and 17 years old. This will be limited to this small spectrum of age to insure better homogeneity in the evaluation of the participants and streamlining of outcome measures. Also, this is the age group for which our measurement tool has been validated.

 Occurrence of a mTBI as defined by the presence of a head trauma, a Glasgow coma scale of 13 to 15 and at least one of the three following criteria4 :

 Any period of loss of consciousness.

 Any loss of memory for events immediately before or after the accident.

 Any alteration in mental state at the time of the accident (eg, feeling dazed, disoriented).

 And the absence of the following criteria:

 Post-traumatic amnesia greater than 24 hours.

 Glasgow Coma Scale < 13, 30 minutes post accident.

 The trauma occurred in the preceding 24 hours.

Exclusion criteria: :

 1. Inability to obtain a proper written informed consent (language barrier, absence of a parental authority, developmental delay, intoxication, patient too confuse to consent according to the treating physician).

 2. Known allergic reaction or intolerance to ondansetron. 3. Known rhythm or cardiac problem, or history of sudden death in the proximal family 4. Patients who are taking a medication which could increase the QT interval. 5. Patients who received ondansetron in the previous 24 hours 6. Any abnormality on radiological studies, including any bleeding in the brain or skull fracture.

 7. Multi-system injuries with treatment requiring admission to hospital or procedural sedation in the ED.

['Traumatic Brain Injury', 'Brain Concussion']


Effect Observation Study of COX-2 Inhibitor to Treat Primary Hypertrophic Osteoarthropathy

Summary: The purpose of this study is to determine whether COX-2 inhibitor is effective in the treatment of primary hypertrophic osteoarthropathy
Inclusion criteria: inclusion criteria:

 diagnosed with primary hypertrophic osteoarthropathy clinically

 over 16 years old

 no other medication intake

 informed consent signed

Exclusion criteria: :

 below 16 years old

 active gastric ulcer

 inflammatory bowel disease

 New York Heart Association classification（NYHA） II to IV

 liver or renal failure

 allergic to nonsteroid anti-inflammatory drugs

 not willing to participate


Identifying Driving Risk Factors in Type 1 Diabetes and Their Reduction Via Internet Program (DiabetesDriving.Com)

Summary: This study will recruit drivers with Type 1 diabetes from across the U.S. and assign them to four groups based on their presumed risk level- routine care low risk, routine care high risk, or to one of two Internet interventions focused on reducing hypoglycemia driving. All subjects will be followed for two years to determine whether and which intervention was most effective at reducing hypoglycemia related driving collisions.
Inclusion criteria: inclusion criteria:

 Have been diagnosed with Type 1 diabetes for at least one year

 Started taking insulin less than a year after being diagnosed with Type 1 diabetes

 Measure blood glucose at least twice a day

 Legal and valid driver's license

 Drives greater than 5,000 per year

 Regular access to the Internet, either through family computer or another readily accessible computer

 Age 18 - 70 years

 English speaker

Exclusion criteria: :

 Type 2 diabetes

 Does not take insulin

 Does not drive

 Does not have legal and valid driver's license

 Does not have routine access to the internet


Metabolic Changes in Hypothyroid Patients

Summary: Hypothyroidism is a frequent condition in danish women, but often overlooked. Along with fatigue one of the main symptoms is weight gain as a result to significantly decreased energy expenditure.~This study was undertaken to elucidate changes in glucose, lipid and amino acid turnover in these patients.
Inclusion criteria: inclusion criteria:

 Newly diagnosed hypothyroidism with tsh over 40 mU/L, etiology chronic autoimmune thyroiditis

 Healthy controls matched regarding sex, age and body mass index

Exclusion criteria: :

 Pregnancy, breastfeeding


Quality of Life in Endometriosis - a Case Control Study

Summary: Endometriosis, one of the most common diseases of women during their reproductive period., may present a chronic disabling disease with major impact on women's life. Therapeutic options are limited and recurrence of disease symptoms is frequent.~The current study investigates the quality of life and several risk factors for the development of endometriosis as well as satisfaction with medical support in a minimum of 600 women with different stages of endometriosis and the same number of control women matched for age (± 3 years) and nationality. To evaluate specific features of endometriosis-associated pain a second group of 100 women with chronic abdominal/pelvic pain not related to endometriosis is investigated. Recruitment takes place in different university clinics, and districts hospitals in Switzerland, Germany. And Austria. Control women i.e. women without any evidence for endometriosis presenting for annual routine gynaecological controls are collected at the same places.~A composition of different internationally validated questionnaires as well as specific questions on dealing with endometriosis is used to collect information on the quality of life and potential risk factors for endometriosis. Questions on sexuality and partnership are also distributed to women's partners. All diagnosis of endometriosis and classification of ASRM (American Society for Reproductive Medicine) disease stages are based on woman's medical charts.
Inclusion criteria: inclusion criteria:

 female >18 years fluent German

 Cases: diagnosis of endometriosis Control 1: no endometriosis, no chronic pain Control 2: no endometriosis, chronic abdominal/pelvic pain

Exclusion criteria: :

 male (Except for partner questionnaires)

 <18years

 not fluent in German

['Endometriosis', 'Quality of Life', 'Pain', 'Sexuality', 'Anxiety', 'Depression', 'Infertility']

Endometriosis
Quality of Life
Pain
Sexuality
Anxiety
Depression
Infertility


Adult Dengue Platelet Study

Summary: Retrospective data in children with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), and in adults with dengue fever (DF), suggested a lack of benefit from prophylactic platelet transfusion for severe thrombocytopenia in dengue patients without bleeding. However, in Taiwan and Singapore, platelet transfusion was given to 13-50% of hospitalised dengue patients. This is a prospective randomised study to examine the safety and efficacy of prophylactic platelet transfusion in adults with dengue and severe thrombocytopenia without bleeding.~The hypotheses are:~Prophylactic platelet transfusion is safe in hospitalised dengue patients with severe thrombocytopenia.~Prophylactic platelet transfusion is effective in preventing bleeding in hospitalised dengue patients with severe thrombocytopenia.
Inclusion criteria: inclusion criteria:

 Age ≥ 21years

 Probable or confirmed dengue

 a) Confirmed dengue: laboratory confirmation of acute dengue by either i) positive polymerase chain reaction (PCR) for viral ribonucleic acid (RNA), or ii)positive NS1 antigen test with a compatible clinical syndrome b) Probable dengue: Positive acute dengue serology and clinical presentation fulfilling either WHO 1997 or 2009 criteria for probable dengue.

 i) 1997 criteria: Acute febrile illness and two or more of the following:

 headache,

 retro-orbital pain,

 myalgia,

 arthralgia,

 rash,

 hemorrhagic manifestations,

 leucopoenia ii) 2009 criteria: Fever and two of the following:

 nausea/vomiting,

 rash,

 aches/pains,

 positive tourniquet test,

 leucopoenia,

 one or more warning sign

 abdominal pain/tenderness,

 persistent vomiting,

 clinical fluid accumulation,

 mucosal bleed,

 lethargy/restlessness,

 liver enlargement >2cm,

 increase in haematocrit concurrent with rapid decrease in platelet count

 Platelets ≤ 20x103/μL
Exclusion criteria:

['Platelet transfusion', 'Supportive care']


Safety and Pharmacokinetics Study of Oral Lithium in Patients With Chronic Spinal Cord Injury

Summary: The current study is a phase I open-label clinical trial to examine plasma levels after oral lithium treatments in 20 subjects with chronic spinal cord injury. The subjects will receive standard doses of oral lithium used in treatment of manic depression. The goal of the trial is to show feasibility and safety of maintaining plasma levels of 0.6 mmol/L to 1.2 mmol/L for six weeks in subjects with chronic spinal cord injury.
Inclusion criteria: inclusion criteria:

 Subjects of either gender and 18 - 60 years of age (preferably 10 males and females each)

 Subjects with chronic spinal cord injury (defined as 12 months or more post spinal cord injury), as confirmed by a MRI

 Subjects with neurological status: ASIA A, B or C

 Subjects must be able to read, understand, and complete the VAS

 Subjects who have voluntarily signed* and dated* an informed consent form, approved by an IEC/IRB, prior to any study-specific procedures *If a subject consents to participation but is not in a position to personally sign and date the informed consent form because of his or her physical condition, the consent must be confirmed at the time of consent orally, signed on behalf by the subject's relative, and by an impartial witness who is present throughout the whole informed consent process.

Exclusion criteria: : Subjects are excluded if they have

 a history of hypersensitivity to lithium

 significant renal, cardiovascular, hepatic and psychiatric diseases

 significant medical diseases or infection

 brain injury

 Addison's disease

 debilitation or dehydration

 recently taken or are taking diuretics or other drugs with known interaction with lithium, such as tricyclic antidepressants, NSAIDs and tetracycline

 a history of alcohol abuse or drug abuse, or if they are

 pregnant or lactating women;

 female of childbearing potential and are unwilling to use an effective contraceptive method while enrolled in the study;

 subjects who are currently participating in another investigational study or have been taking any investigational drug within the last 4 weeks prior to screening of this study (Visit 1); and finally,

 any criteria, which, in the opinion of the investigator, suggest that the subject would not be compliant with the study protocol.


Safety and Effectiveness of Botulinum Toxin in Elderly Patients With Dementia and Muscle Stiffness

Summary: Aim of the study is to perform a pilot study to assess the impact of Botulinum toxin on muscle tone, and caregiver burden in individuals who are cognitively impaired and who are fully dependent.~The primary objective is to confirm proof of principle that paratonic rigidity and the consequences associated with it can be reduced with injection of Botulinum toxin injections resulting in reduced care-giver burden.~The secondary objectives are to determine optimal time points for evaluation of efficacy in this patient population and whether the time period is sufficient for washout of Botulinum toxin effect; determine most salient and sensitive outcome measures; identify obstacles in data gathering; and lastly, to determine feasibility of battery of assessments in this pilot study.
Inclusion criteria: inclusion criteria:

 Severe cognitive impairment (complete dependency in all activities of daily living (ADLs)

 Diagnosis of Alzheimer's disease, vascular dementia,or frontotemporal dementia

 Score> 3 on the paratonic assessment instrument, with paratonic rigidity in an arm(s) interfering in the provision of care

Exclusion criteria: :

 Alternate etiologies for increased tone

 Botulinum toxin 6 months preceding the study


NUCYNTA (Tapentadol Immediate Release) Versus Oxycodone Immediate Release in the Treatment of Acute Low Back Pain

Summary: Evaluate how NUCYNTA (tapentadol) immediate release (IR) compares with oxycodone IR in the treatment of acute low back pain.
Inclusion criteria: inclusion criteria:

 At Visit 1 (study entry) patients must have a medical history and physical and neurological examinations that support a clinical diagnosis of acute low back pain that is felt down to the lower leg below the knee with the onset no longer than 30 days before Visit 1

 At Visit 1 patients must report qualifying pain intensity scores

 Patients must be appropriate candidates for treatment with oral opioid pain medication in the investigator's clinical judgment

 Patients must be able to appropriately verbalize pain characteristics and to complete all protocol required measurements/assessments without assistance

 Patients must be medically stable on the basis of physical examination, medical history, vital signs, and clinical laboratory tests performed at screening

Exclusion criteria: :

 History of back (cervical, thoracic or lumbosacral) pain =50% of the time in the 1 year prior to the first visit

 History of any low back pain episode, with the exception of the current acute low back pain episode, within 3 months prior to the first visit that was greater than mild in pain intensity, or was associated with disability (e.g., loss of time from work, family, or activities of daily living), or necessitated the use of an opioid (narcotic) analgesic including tramadol

 Medical history or physical examination results that suggest the acute low back pain or any of the neurological symptoms or signs are caused by a serious medical condition (e.g., fever, chills, unexplained weight loss, bowel or urinary bladder dysfunction or incontinence, bilateral leg weakness, progressive weakness, paralysis)

 There is a high probability for surgical intervention for the back pain during the projected time on the study or that there will be an increase in the severity of the leg pain or deficits

 Had either a surgical procedure involving the spine or intervertebral discs in the lower back region within 1 year prior to Visit 1 or had >1 surgical procedure(s) involving the spine or intervertebral discs in the lower back region

 has any painful condition that could interfere with the study assessments or with the patient's ability to differentiate the pain associated with the acute low back pain episode from pain associated with another condition

 History of severe lumbar spinal stenosis, fibromyalgia, or ankylosing spondylitis

 history of epilepsy or recurrent seizures

 Unable or unwilling to discontinue all prohibited medications at the time of randomization and during the time of their participation in the study

 Known or suspected history of alcohol or drug abuse based on medical history, physical examination, urine drug screening, or the investigator's clinical judgment

 History of cancer malignancy within 2 years prior to the first visit, with the exception of basal cell skin carcinoma

 Have filed or plan to file a worker's compensation claim for any issue related to the current acute low back pain episode

 Currently involved in litigation or plan to seek legal recourse for any issue related to their acute low back pain

 Known allergies, hypersensitivity, or intolerance to tapentadol or the comparator (oxycodone) or any excipients used in their manufacture

 Had previously been enrolled in a tapentadol clinical study

 is pregnant or are breast-feeding

['Pain', 'Back Pain', 'Low Back Pain', 'Back Pain With Radiation']

Pain
Back Pain
Low Back Pain
Back Pain With Radiation


Study of Lung Proteins in Patients With Pneumonia

Summary: This study will examine the different types of proteins present in the lungs of patients with pneumonia to explore the causes of different types of the disease. Pneumonia is a condition that causes lung inflammation AND is often caused by an infection. It is usually diagnosed by lung x-rays and listening to the chest with a stethoscope. This method can diagnose pneumonia, but it does not provide information on the cause of the inflammation - information that might be helpful in guiding treatment. This study will measure proteins in the lungs of patients to see if certain proteins are associated with specific forms of pneumonia, and can thus serve as biomarkers for disease.~Patients undergoing diagnostic bronchoscopy at the NIH Clinical Center may participate in this study. Patients will undergo bronchoscopy and bronchoalveolar lavage as scheduled for their medical care. For this procedure, the patient's mouth and throat are numbed with lidocaine; a sedative may be given for comfort. A thin flexible tube called a bronchoscope is advanced through the nose or mouth into the lung airways to examine the airways carefully. Saline (salt water) is then injected through the bronchoscope into the air passage, acting as a rinse. A sample of fluid is then withdrawn for microscopic examination. Researchers in the current study will use some of the fluid obtained from the lavage to examine for protein content.~In addition to the bronchoscopy and bronchoalveolar lavage, participants will have about 2 tablespoons of blood drawn to compare blood test results with the results of the lung washings. Patients' medical records will be reviewed to obtain information on past medical history, current medical treatment, vital signs, and results of x-ray tests.~...
Inclusion criteria: inclusion criteria:

 All eligible patients undergoing diagnostic bronchoscopy who provide consent for proteomic analysis of BAL fluid supernatant and chart review of patient characteristics will be included in this study.

 A parent/guardian may provide consent for a child age 17 or under and a Legally Authorized Representative (LAR) may provide consent for adults unable to consent.

Exclusion criteria: :

 Patients undergoing bronchoscopy but not wanting to participate with either the chart review or the proteomic analysis of BAL fluid supernatant will be excluded.

['Pneumonia', 'Pulmonary Disease', 'Lung Disease']

Pneumonia
Pulmonary Disease
Lung Disease


Pain Management in Geriatric Hip Fracture

Summary: The Null Hypothesis is that there is no association between Pain regime and the functional performance among geriatric patients having traumatic hip fracture. Two limbs are being assessed:1. Three weeks of regular oral Panadol and Tramadol after hip fracture 2. Oral Panadol and tramadol taking in p.r.n. basis. Functional outcome including Numerical Rate Scale for pain assessment, Functional Independency Measure and Elderly Mobility Score are chosen.
Inclusion criteria: inclusion criteria:

 Both sex of Age > 65

 Traumatic non-pathological fracture neck of femur or trochanteric or subtrochanteric fracture having operative intervention

Exclusion criteria: :

 Age < 65

 Pathological fracture

 Multiple lower limb fractures

 Old fracture

['Paracetamol tablet and Tramadol capsule', 'Panadol 500mg tablet, tramadol 50mg capsule']

Paracetamol tablet and Tramadol capsule
Panadol 500mg tablet
tramadol 50mg capsule

['Geriatric Hip Fracture Pain Management']


Adoptive Immunotherapy for CMV Disease

Summary: Treatment strategy of patients:~Stem cell engraftment (myeloablative or NST) for induction of host vs graft myeloablative transplantation tolerance.~Whenever indicated, additional post NST DLI given in graded increment, to optimize control of GVHD.~Preparation of immune donor lymphocytes, either by donor immunization in-vitro with a CMV-specific peptide followed by administration of immunized donor lymphocytes, or by injection of donor lymphocytes and in-vivo sensitization of donor lymphocytes in the patient following DLI.~Pre-emptive treatment of seronegative patients at risk or patients with documented viremia or CMV disease with CMV-specific donor lymphocytes generated in-vivo in the donor or in the host by peptide immunization.~Consenting donors will be immunized with CMV-specific peptides, for induction of CTLs in-vivo following subcutaneous inoculation of peptides with adjuvant or donor APC pulsed with relevant peptides.
Inclusion criteria: inclusion criteria:

 For Patient:

 Consenting patients with indication for myeloablative BMT or NST with an HLA matching sibling available, for transplant.

 Patients at risk of CMV disease including seronegative patients; patients with seronegative donors, and seronegative donor for sero positive patients.

 Patients with resistant CMV viremia or CMV disease not responding to conventional treatment with ganciclovir, or Foscarnet.

 Patients with HLA phenotype for which a relevant peptide for CMV exists.

 For Donor:

 Consenting sibling >18 years old.

 HLA phenotype for which a relevant peptide for CMV exists.

Exclusion criteria: :

 For Patient:

 Patients with severe resistant GVHD where there may be a risk to administer DLI or immunized donor lymphocytes.

 For Donor:

 Consenting sibling >18 years old.

 HLA phenotype for which a relevant peptide for CMV exists.

 Donor with an infectious disease (e.g. HIV-1; HBV, etc.)


A Trial of Non-operative Versus Operative Management of Olecranon Fractures in the Elderly

Summary: Proximal forearm fractures comprise approximately 5% of all fractures, with olecranon fractures accounting for almost 20% of thes fractures. There is limited conclusive evidence regarding the optimal treatment and outcome of these fractures within the elderly population with one case series in the literature describing 13 patients. Our trial includes all patients equal to or over the age of 75yrs presenting to the Edinburgh and Fife Orthopaedic Trauma Units with an isolated olecranon fracture. Patients who consent to enrol in the trial will be randomised to operative fixation using one of two treatment methods. Patients in the nonoperative group will be place in a sling for two weeks and then allowed to mobilise under supervised physiotherapy as per normal protocol. For those patients in the operative group, tension band wire of plate fixation will be employed depending on the choice of their supervising consultant. Patients will be evaluated over a one year period following their treatment.
Inclusion criteria: inclusion criteria:

 Age ≥75 years

 Minimal, moderate or severe fragmentation of the olecranon

 Within two weeks of olecranon fracture

Exclusion criteria: :

 Patients unable to give informed consent

 Associated fractures to the coronoid, radial head and/or distal humerus

 Associated ligamentous injury, dislocation or subluxation

 Open fractures


Effect of SACCHACHITIN on Healing of a Chronic Wound

Summary: SACCHACHITIN gel, prepared from the waste residue of the fruiting body of Ganoderma tsugae, was used in a previous study to enhance skin wound healing in animal models. In the present study, the effects of the gel on the activity of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) as well as on the healing of skin wounds in humans are estimated by a clinical trial.~The hypothesis regarding the poor healing of the wound is the over-expression of MMP and the inhibition of the angiogenic factors. From the previous animal study, the effect of SACCHACHITIN was to inhibit the activity of MMP and stimulation of VEGF and we try to prove the effect over the human wounds from this clinical trial.~Patients with a poorly healed wound, in which skin graft is clinically indicated, are included in this study. The exudates from the wound are collected and analyzed for the activity and concentration of VEGF and MMP. The change of the healing process is recorded.~Positive results are expected from the clinical trial and the patients will get another choice for the treatment of the chronic wound other than skin grafting.
Inclusion criteria: inclusion criteria:

 Patients with a poorly healed wound, in which skin graft is clinically indicated

Exclusion criteria: :

 Skin infection

 Vital signs unstable

:

 Skin infection

 Vital signs unstable


Group Psychotherapy Among Congestive Heart Failure Patients

Summary: This study will examine the efficacy of group therapy utilizing the Existential Approach in heart failure patients when compared to a control group of patients who are waiting for the same group treatment. This comparison will be achieved by measuring changes in the variables studied namely, the levels of psychological distress and levels of psycho-social adjustment.
Inclusion criteria: inclusion criteria:

 Clinical diagnosis of heart failure at levels III and IV, according to the classification of the NYHA (New York Heart Association) for 3 months or more.

 Clinical diagnosis of LVEF less than 50% or were on diuretic therapy for more than three months with at least one previous hospitalization due to heart failure disease.

Exclusion criteria: :

 uncertain prognosis for 12 months due to other conditions.

 acute coronary disease in recent months.

 existence of another life-threatening illness of the patient (such as active cancer, chronic kidney failure).

 severe neurological problem (Brain syndrome / orientation problem/ difficult peripheral neuropathy).

 severe mental illness (active psychosis / suicide risk / severe dementia).

 linguistic limitations (such as misunderstanding of the Hebrew language / stuttering / untreated audio impairment).

 a significant functional problem (such as unconsciousness / connection to respiration device / confined to a wheelchair or bed / severe walking disability / needs help with complete basic daily activities).

 objective limit that endangers liability for participation in the seven meetings (such as remote residential / tourist / convict / drug addict).

 subjects whose mother tongue is not Hebrew.


A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV Lupus Nephritis

Summary: This was a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab in combination with mycophenolate mofetil (MMF) compared with placebo in combination with MMF in subjects diagnosed with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis.
Inclusion criteria: inclusion criteria:

 Diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria.

 Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (LN), with either active or active/chronic disease.

 Proteinuria.

 16-75 years of age.

Exclusion criteria: :

 Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE.

 Unstable subjects with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions.

 Lack of peripheral venous access.

 Pregnancy or lactation.

 History of severe allergic or anaphylactic reactions to monoclonal antibodies.

 Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude subject participation.

 Concomitant chronic conditions, excluding SLE (eg, asthma, Crohn's disease) that require oral or systemic corticosteroid use in the 52 weeks prior to screening.

 History of renal transplant.

 Known human immunodeficiency virus (HIV) infection.

 Known active infection of any kind (but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives within 4 weeks of randomization or oral anti-infectives within 2 weeks of randomization.

 History of deep space infection within 1 year of screening.

 History of serious recurrent or chronic infection.

 History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinomas of the skin that have been treated or excised and have resolved).

 Currently active alcohol or drug abuse or history of alcohol or drug abuse within 52 weeks prior to screening.

 Major surgery requiring hospitalization within 4 weeks of screening (excluding diagnostic surgery).

 Treatment with cyclophosphamide or calcineurin inhibitors within the 90 days prior to screening.

 Use of mycophenolate mofetil (MMF) at a dose of > 2 grams daily for longer than the 90 days prior to screening.

 Intolerance or history of allergic reaction to MMF.

 Intolerance or history of allergic reaction to both angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers.

 Use of oral prednisone (or corticosteroid equivalent) at a dose of > 20 mg/day for longer than the 14 days prior to screening.

 Previous treatment with CAMPATH-1H (alemtuzumab).

 Previous treatment with a B-cell targeted therapy.

 Treatment with any investigational agent (including biologic agents approved for other indications) within 28 days of the start of the screening period or 5 half-lives of the investigational drug (whichever is longer).

 Receipt of a live vaccine within the 28 days prior to screening.

 Intolerance or contraindication to oral or IV corticosteroids.

 Current therapy with a nonsteroidal anti-inflammatory agent.

 Positive hepatitis B sAg or hepatitis C serology.

['Rituximab', 'Placebo', 'Mycophenolate mofetil', 'Methylprednisolone', 'Diphenhydramine', 'Acetaminophen', 'Prednisone']

Rituximab
Placebo
Mycophenolate mofetil
Methylprednisolone
Diphenhydramine
Acetaminophen
Prednisone


Comparing Use of a Prehospital Ultrasound System and Standard Prehospital Care in Thoracoabdominal Trauma

Summary: The NanoMaxx Ultrasound System (SonoSite) in connection with the RP-Xpress (InTouch Technologies) provides a means of transmitting ultrasound images, video, and audio to a remote location in real-time. It has been envisioned that this system be used to diagnose trauma patients with suspected pleural effusion, hemothorax, pneumothorax, or abdominal blockage during prehospital care; under the guidance of in-hospital physicians, paramedics would perform an Focused Assessment with Sonography for Trauma (FAST) examination while trauma patients are transported to hospital via ambulance. The investigators hypothesize that in-hospital physicians interpreting ultrasound images obtained by paramedics during trauma patients' transportation to hospital will reduce time to diagnosis; thus, preparations by emergency physicians, surgeons, and operating room teams to receive critically injured patients may begin earlier, reducing time to intervention during a critical period in patient care. Data will also be collected regarding quality of images obtained in-ambulance and the interaction between paramedics and physicians using the remote-presence system.
Inclusion criteria: inclusion criteria for FAST cohort:

 Patient is 18 years of age or older

 Patient presenting with blunt or penetrating trauma to the thorax or abdomen

 Patient transported by MD Ambulance to Royal University Hospital

 Patient being transported by a paramedic who has received training in the above ultrasound system and who has with them a NanoMaxx Ultrasound System (SonoSite) to be used in connection with the RP-Xpress (InTouch Technologies)

 Patient will take longer than 10 minutes to transport to hospital

 Patient's care will not be compromised in completing a FAST exam - opinion of paramedic

 Patient's care will not be compromised in completing a FAST exam - opinion of ER physician

 inclusion criteria for Controls:

 Patient is 18 years of age or older

 Patient presenting with blunt or penetrating trauma to the thorax or abdomen

 Patient transported by MD Ambulance to Royal University Hospital

 Patient will take longer than 10 minutes to transport to hospital

Exclusion criteria: :

 Patients under the age of 18

 Patients whose care would be compromised if other procedures of higher priority (as determined by paramedics and/or remotely-present physicians) were not be able to be executed due to time involved in completing a FAST exam

 Patients who are not being transported to Royal University Hospital

 Patients whose expected transport time from scene to hospital is less than 10 minutes

['Thoracoabdominal Trauma', 'Focused Assessment With Sonography for Trauma (FAST)', 'NanoMaxx Ultrasound System (SonoSite)', 'RP-Xpress (InTouch Technologies)']


The Effect of Different Types of Temporary Abdominal Closure on Intra Abdominal Hypertension.

Summary: This is a prospective comparison trial. Patients that will be included in the trial are those that will have operations in which their abdominal closure is temporary, i.e. patients sustaining trauma or septic abdomen.~Patients will be grouped according to the method of temporarily abdominal closure (TAC) procedure:~Vacuum-assisted closure (VAC)~Bogota bag (BB), a sterile intravenous bag silo closure. The two methods are currently accepted with no clear cut evidence to prefer one on another. At Soroka Medical Center the decision to choose either of the methods is at the surgeon's discretion.~Intra-abdominal pressure will be measured in all patients by the urinary bladder pressure technique at 6 12 24 ant 48 hours post operation. The measurement is a routine procedure done as part of the monitoring processes of critically ill patients in the General Intensive Care Unit (GICU).~Patients will be evaluated for the development of acute intra abdominal hypertension with or without abdominal compartment syndrome.
Inclusion criteria: inclusion criteria:

 Adults male or female over 18 year old undergoing emergency laparotomy. Patients that have their abdominal wall closed at the end of surgery by a temporary closure technique.

Exclusion criteria: :

 Patients that according to the surgeon estimates will not survive 24 hours.

['Intra Abdominal Hypertension', 'Abdominal Compartment Syndrome']

Intra Abdominal Hypertension
Abdominal Compartment Syndrome


Cohort Study to Investigate the Association Between Changes in Brain Volume and Postoperative Cognitive Dysfunction

Summary: Despite an ongoing controversy in the scientific literature, the link between anesthesia and dementia and/or cerebral atrophy remains unclear. Recent retrospective data suggests an association of surgery with a reduction in brain volume. With the present prospective cohort study, we would like to reproduce and verify these results, and investigate a possible association with the postoperative cognitive performance.~We will measure cerebral gray matter volumes in elderly patients before, 3 and 12 months after major non-cardiac surgery and determine cognitive functions at the same time.~Study hypothesis:~Surgery under general anesthesia in elderly patients is associated with a loss of gray matter.~The degree of cognitive dysfunction is associated with the loss of grey matter in brain areas relevant for cognitive functions.
Inclusion criteria: inclusion criteria:

 Age ≥ 65 years

 Elective major surgery

 Planned general anesthesia

Exclusion criteria: :

 Cardiac surgery

 Neurosurgery including carotid endarterectomy

 Preoperative Mini Mental State (MMS) Examination Score < 24

 Previous pathological neuroimaging (if available)

 History of cerebral or cerebrovascular pathology

 Chronic use of psychiatric medication

 Alcohol or substance abuse

 A history of chronic pain unrelated to the planned surgery

 Any contraindication for MRI (e.g. pacemakers and other MR-incompatible metal implants)

 Claustrophobia

 Lack of informed consent

['Postoperative Cognitive Dysfunction', 'Delirium', 'Dementia']

Postoperative Cognitive Dysfunction
Delirium
Dementia


Building Capacity for Sustainable Livelihoods and Health

Summary: Despite recent economic growth in Ghana, the prevalence of childhood malnutrition remains high. Wasting prevalence affected 29% among 6- to 8-months-old infants in 2008. Poor nutrition contributes to about one-third of child mortality, diminishes cognitive development, and is a major determinant of maternal mortality. The specific objectives of the 5-year project are to: (1) enhance human capacity of government, civil, and private institutions through improvement of knowledge and skills of personnel in agriculture, nutrition and health, entrepreneurship, and pedagogy; (2) identify information needs of local institutions that are not presently met and develop a representative and sustainable longitudinal data system to support evidence-based decision-making in programs; (3) increase vulnerable households' access to quality services in agriculture/fisheries, nutrition and health, and finance; (4) implement integrated intervention activities to improve infant and young child and adolescent nutrition outcomes; and (5) examine differential benefits of the interventions for diverse vulnerable populations. The project comprises two major activities: part I - the creation of a longitudinal data system to support evidence-based decision-making in programs, and part II - the implementation of intervention activities to improve nutrition outcomes.~The survey will include demographic, socioeconomic, health, diet, and nutritional status information collected annually from a representative same of 1500 households with infants (0-12 mo) and 1500 households with adolescents (9-12 y). The data will be analyzed and presented rapidly each year to district program and policy leaders to assist them in developing their activity plans for the following year.
Inclusion criteria: inclusion criteria:

 household with infant < 12 mo or adolescent 10-15 y

 Living in selected communities of Upper Manya Krobo District (Ghana)

Exclusion criteria: :

 infant or adolescent has medical condition that limits dietary intakes or growth

['Nutrition and agriculture', 'Iron-rich food & business literacy']

Nutrition and agriculture
Iron-rich food & business literacy


Recombinant Human Interferon a-2b Gel for HPV Gynecological Infections

Summary: to assess the efficacy and safety of recombinant human interferon α-2b gel (Yallaferon®) for the treatment of patients with cervical high-risk HPV infections; to analyze the HPV type infections and clinical negative conversion.~285 patients with positive high risk HPV infection were randomized into interferon gel group and control group at ratio of 2:1 (203 patients in treatment group and 82 patients in control group). The patients in treatment group received 1g recombinant human α-2b interferon gel every other day for consecutive 3 courses of treatment, whereas no treatment was conducted in control group.
Inclusion criteria: inclusion criteria:

 Age 30 to 65 years of age the sex life of female patients;

 , liquid-based cytology (TCT) check no intraepithelial lesions and malignant cells;

 , HPV DNA typing test for high-risk HPV positive (including a single high-risk type positive, and more high-risk type of positive and high-and low-risk hybrid positive).

 15 kinds of high-risk types, including HPV16, 18,31,33,35,39,45,51,52,53,56,58,59,66,68

Exclusion criteria: :

 (1) cervical intraepithelial neoplasia (CIN); (2), combined with a severe fungal, trichomonas vaginitis; (3), severe primary diseases associated with cardiovascular, liver, kidney and hematopoietic system; (4), allergies or allergy to the drug known ingredients. (5), within 30 days to accept other clinical trials of drugs or are participating in clinical trials; (6), pregnant and lactating women and to be pregnant women; (7), the researchers do not consider it appropriate clinical trials.


Myometrial Thickness as a Predictor for the Latency Interval in PPROM

Summary: 100 women divided into 3 groups:~Group I: included 50 women with preterm premature rupture of membranes (PPROM, n=50) with gestational age from 24 to 34 weeks.~Group II: included 25 term non-labor control (T-CTR, n=25) with gestational age from 37 to 41 weeks.~Group III: included 25 preterm non-labor control (P-CTR, n=25) with gestational age from 24 to 34 weeks.The myometrial thickness at 4 different sites9:~a) The lower uterine segment (LUS): 2cm above the reflection of the full urinary bladder (b)The anterior wall: 1cm above the maternal umbilicus. (c)Fundus: by placing the scan probe perpendicularly above the uterine fundus so that the entire curvature of the uterus was visualized.~(d)The posterior wall: through using the maternal abdominal aortic pulsation as an anatomic marker.~At least 3 measurements were obtained at each site and averaged. The latency interval is determined in each of the 3 groups.
Inclusion criteria: inclusion criteria:

 singleton pregnancy with a definite history of current PPROM for the study group

Exclusion criteria: :

 Suspected fetal growth restriction (IUGR),

 Any gross fetal anomalies,

 Abnormalities of placentation,

 Uterine structural abnormalities,

 Fetal jeopardy or intrauterine fetal death (IUFD).

 Women presenting with chorioamniointis with fever over 38 c abdominal tenderness, foul vaginal discharge and/or fetal tachycardia.

 Diabetics, immunocompromized and cardiac patients.

 Women with cervical cerclage.

 Women with drained liquor


Vitamin K as Additive Treatment in Osteoporosis

Summary: Vitamin K is thought to be important for bone health because it activates several proteins involved in bone formation. Poor dietary intake of vitamin K (mainly found in dark green leafy vegetables) is associated with bone loss and fractures. Giving supplements of the main dietary form of vitamin K (called K1) or another common form which our bodies make from K1(called MK4), to improve bone health have given mixed results. This confusion is thought to have arisen because these studies involved people who already had enough vitamin K or did not have osteoporosis. We want to test the hypothesis that treatment with bisphosphonates combined with vitamin K, in vitamin K deplete elderly women with osteoporosis, may offer additional benefit on skeletal metabolism and reduction of fracture risk. We want to test this by measuring vitamin K status in post-menopausal women with osteoporosis who are on the recommended treatment with a bisphosphonate and calcium/vitamin D supplements. Those with low vitamin K will then be recruited to study the effect of supplementation with either K1 or MK4.
Inclusion criteria: inclusion criteria:

 Inclusion in the cross-sectional part of the study which involves assessment of vitamin K status

 Informed consent to screening stage : assessment of vitamin K status

 serum vitamin K concentration < 0.35 ug/ml

 Inclusion into the randomised controlled trial

 1. ambulatory post-menopausal women aged between 55-85 years 2. Post-menopausal osteoporosis ( history of previous fragility fractures or BMD evidence of osteoporosis or osteopenia with at least one clinical risk factors such as low BMI, positive family history of osteoporosis) 3. Treatment with a bisphosphonate and calcium/vitamin D supplements for at least 12 months 4. Informed written consent 5. e GFR >30 ml/min 6. normocalcaemia

Exclusion criteria: :

 Age <55 years, or > 85 years

 Male gender

 severe renal impairment (CKD stage 4 and 5)

 poor mobility (inability to walk 100 yards unaided)

 malabsorption (extensive bowel surgery, short bowel)

 generalised carcinomatosis

 glucocorticoid therapy

 inflammatory disorders (e.g. active rheumatoid arthritis, inflammatory bowel disease requiring oral glucocorticoids),

 endocrine diseases (e.g. primary hyperparathyroidism, hyperthyroidism).

 chronic liver disease

 current treatment with teriparatide, strontium ranelate

 Participation in a trial with an investigational product within the previous 3 months

 Serum vitamin K > 0.35 µg/ml

 patients on anti-coagulants such as warfarin

['Phylloquinone', 'Menatetrenone (MK4)', 'placebo']

Phylloquinone
Menatetrenone (MK4)
placebo


A Study of Two Forms of Pentamidine in the Treatment of Pneumocystis Carinii Pneumonia (PCP) in Patients With AIDS

Summary: To compare parenteral versus inhaled pentamidine in patients with documented Pneumocystis carinii pneumonia (PCP) with AIDS.
Inclusion criteria:
Exclusion criteria:

 Co-existing Condition:

 Patients with the following are excluded:

 Previous history of adverse reaction to pentamidine.

 History of asthma.

 Pulmonary Kaposi's sarcoma.

 Patients with the following are excluded:

 Previous history of adverse reaction to pentamidine.

 History of asthma.

 Pulmonary Kaposi's sarcoma.

 Inability to understand the consent procedure.

 All patients hospitalized at Cedars-Sinai Medical Center with AIDS and possible Pneumocystis carinii pneumonia (PCP) will be eligible.

 Patients with HIV antibody or AIDS and a clinical presentation suggesting PCP are eligible.

['Pneumonia, Pneumocystis Carinii', 'HIV Infections']

Pneumonia
Pneumocystis Carinii
HIV Infections


Sleep, Aging and Risk for Alzheimer's Disease

Summary: Our preliminary data show for in cognitively-normal elderly, that Sleep Disordered Breathing (SDB) is associated with the increase of cerebrospinal fluid (CSF) phosphorylated-Tau (P-Tau) and total-Tau (T-Tau), decreases in medial temporal lobe glucose uptake (FDG-PET) and volume (MRI) and progressive memory decline, all of which have been shown to be useful in predicting future dementia in older adults. These findings raise the question as to whether Alzheimer's disease (AD) tissue damage causes SDB in the elderly, or alternatively, if SDB acts as a risk factor for AD neurodegeneration. In the proposed study, we will investigate these mechanistic hypotheses in cognitively normal elderly by examining the longitudinal associations between SDB and cognitive decline, novel MR neuroimaging and CSF biomarkers for neurodegeneration; while our secondary goal is to launch a pilot treatment study to aid in interpreting the mechanistic hypotheses and to examine the effects of nasal continuous positive airway pressure (CPAP) on cognitive decline and neurodegeneration.
Inclusion criteria: inclusion criteria:

 Male and female subjects with normal cognition and >50 years of age will be enrolled. Younger subjects are not included as the risk for cognitive impairment is too low. Moreover, by selecting this age-range we minimize the possibility of including early-onset genetic forms of neurodegenerative diseases such as Alzheimer's disease and Frontotemporal Dementia.

 Normal subjects will be within normal limits on neurological and psychiatric examinations. All subjects enrolled will have both a Clinical Dementia Rating = 0 and Global Deterioration Scale < 3.

 All subjects will have had a minimum of 12 years education.The education restriction reduces performance variance on cognitive test measures and improves the sensitivity for detecting pathology and disease progression using the robust norms available at NYU School of Medicine.

 All subjects will have an informed family member or life partner interviewed to confirm the reliability of the subject interview. All subjects will agree to the MRI imaging, the lumbar puncture, apolipoprotein E (ApoE) genotyping and DNA banking

Exclusion criteria: :

 Diagnosis of any brain disease or MRI evidence of brain damage including significant trauma, hydrocephalus, seizures, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders). Persons with silent cortical infarcts are excluded. Subcortical infarcts and white matter lesions are not exclusions.

 History of brain tumor.

 Any radiation or chemotherapy anywhere in the body in the past 3-years.

 Significant history of alcoholism or drug abuse.

 History of psychiatric illness (e.g., schizophrenia, mania, PTSD, or life long history of major depression).

 Hamilton Depression Scale >16 only with history of life long depressive episodes. Otherwise not excluded.

 Evidence of clinically relevant and uncontrolled cardiac, pulmonary, or hypothyroid or hematological conditions. Insulin dependent diabetes and/or history or treated hypertension are not an exclusion. Normal subjects with current levels of HbA1c >5.9% or diabetics >7.0% (American Diabetes Association, 2010) and/or current blood pressure levels >140/90 mm Hg (JNC on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, 2003) will be advised to seek referral.

 Physical impairment of such severity as to adversely affect the validity of psychological testing.

 Hostility or refusal to cooperate.

 Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.

 History of a first-degree family member with early onset (before age 65) dementia.

 Medications adversely affecting cognition will result in exclusion. The excluded medications include:

 Antidepressants with anti-cholinergic properties.

 Regular use of narcotic analgesics (>2 doses per week).

 Use of neuroleptics with anti-cholinergic properties.

 Other medications with central nervous system anticholinergic activity.

 Use of Anti-Parkinsonian medications.

 At the baseline individuals taking physician ordered or off-label memory or other cognitive enhancing medications (e.g. cholinesterase inhibitors or memantine) are excluded. At the follow-up these medications are allowed. Also excluded at baseline are individuals taking physician ordered, but off-label memory enhancements. Individuals taking over the counter memory enhancing or protecting medications (e.g. ginkgo biloba, vitamins) are not excluded.

 Patients with significant physical changes (e.g. amputations or loss of sensory input) as these may affect the MRI blood flow measures.

['Continuous positive airway pressure (CPAP)']

['Sleep Disordered Breathing', "Alzheimer's Disease"]

Sleep Disordered Breathing
Alzheimer's Disease


Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia

Summary: In this feasibility trial, the investigators will compare participants treated with montelukast and hydroxyurea to those treated with placebo and hydroxyurea for a total of 8 weeks.
Inclusion criteria: inclusion criteria:

 1)Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis

 2)Males and females age 16 years to 70 years old

 3)Greater than 2 episodes of pain in the last 12 months

 4)On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin

Exclusion criteria: :

 Judged not likely to be study compliant by his/her hematologist

 History of adverse reaction to montelukast or any of the components of montelukast

 Have used medications known to interact with montelukast such as rifampin, phenobarbital, and gemfibrozil within 4 weeks of enrollment

 Currently being treated with a leukotriene antagonist (montelukast or zileuton) or have used montelukast/zileuton within the last 60 days

 Chronic blood transfusion therapy defined as regularly scheduled transfusions.

 Hemoglobin A greater than15% on hemoglobin analysis

 Individuals with a current physician diagnosis of asthma (within last 12 months) or requires continuous supplemental oxygen, or predicted or current use of asthma medications (inhaled corticosteroids, but participants taking bronchodilators will be allowed to participate).

 Current participation in another therapeutic trial for SCD

 Known current pregnancy

 Known history of HIV

 Serum creatinine greater than 3 times the site's upper limit of normal

['Montelukast added to Hydroxyurea', 'Placebo added to Hydroxyurea']

Montelukast added to Hydroxyurea
Placebo added to Hydroxyurea

['Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)']

Sickle Cell Anemia (HbSS
or HbSβ-thalassemia0)


Study to Demonstrate That Antibiotics Are Not Needed in Moderate Acute Exacerbations of COPD

Summary: The ultimate goal is to reduce unnecessary antibiotic prescriptions which drive the development of antibiotic resistance in the community. The primary objective of ABACOPD is to demonstrate in a sufficiently sized clinical study that there is no relevant increase in the failure-rate for patients with acute moderate exacerbations of COPD (AE-COPD) treated with placebo instead of antibiotic treatment both on top of standard of care. A patient is classified as treatment failure if additional antibiotic therapy is required during treatment period or until the test of cure visit (TOC at day 30, primary endpoint).
Inclusion criteria: inclusion criteria:

 Adults, either sex, older or equal than 40 years of age

 For female patients, the following conditions are to be met:

 has been postmenopausal for at least 1 year, or

 is surgically incapable of bearing children, or

 is of childbearing potential, and the following conditions are met:

 has a negative pregnancy test (urine- or serum-based) immediately before study entry (i.e., before the start of treatment or any other study procedure that could potentially harm the fetus), and one or more of following criteria

 must agree to abstinence or use an accepted method of contraception. The subject must agree to continue with the same method throughout the study.

 having only female sexual partners

 sexual relationship with sterile male partners only

 Patients diagnosed with COPD stages I-IV as defined by the Global initiative for chronic Obstructive Lung disease (GOLD).

 and

 Doctor's diagnosis of acute (onset < 7 days) moderate exacerbation of COPD defined by a sustained worsening of the patient's condition (including at least 2 of the following symptoms: increased dyspnea, increased sputum production, sputum purulence and increased cough), from the stable state and beyond normal day-to-day variations, necessitating a change in regular medication in patient with underlying COPD, needing additional medical assistance.

 Absence of community acquired pneumonia or lower respiratory tract infection with a clear indication for antibiotic treatment as determined by Procalcitonin level < 0.25 ng/mL and/or absence of pulmonary infiltrates on routine chest x-ray.

 Smoking history of at least 10 Pack Years or more.

 Patients must be able to complete diaries and quality of life questionnaires.

 Patients must sign and date an informed consent prior to any study procedures.

Exclusion criteria: :

 Severe exacerbation: defined by need for ventilatory support (indicated by severe dyspnea with failure to respond to emergency treatment and/or persistent hypoxemia (PaO2 <50 mm Hg despite O2 administration and / or respiratory acidosis (pH <7.35 and PaCO2> 45mmHg)) or mental confusion or circulatory insufficiency (need of vasopressors)

 Fever (>38.5°C)

 Known impaired hepatic or renal function

 Active or suspected tuberculosis infection of the respiratory tract

 Acute exacerbation of asthma

 Suspected or known hypersensitivity to, or suspected serious adverse reaction to sultamicillin; suspected or known hypersensitivity to penicillins or cephalosporins

 Immunosuppression or Immunosuppressive therapy (cytostatic chemotherapy within last 28 days or neutropenia (neutrophils < 1000/µ)l; systemic corticosteroids (≥20 mg prednisolon equivalent/day > 14 days; HIV-infection; immunosuppression after organ- or bone marrow transplant)- Patients with metastatic or hematological malignancy, splenectomized patients or patients with known hyposplenia or asplenia

 Oral/parenteral antibiotic use within 30 days prior to randomization (a singular administration of antibiotics prior to randomization is allowed)

 In-patient treatment within the last 30 days

 An antibiotic is clearly indicated for treatment of a known infection

 Known MRSA (methicillin-resistant Staphylococcus aureus) colonization or infection

 Patients with known bronchiectasis

 Patients with known bacterial airway colonization (>3 positive sputum cultures in the previous year)

 Progressively fatal disease, or life expectancy ≤6 months

 Mononucleosis

 Lymphatic leukemia

 Severe gastro-intestinal disorders with vomiting and diarrhea

 Women who are breast feeding

 Patients who have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow up phase.

 Patients with mental conditions rendering them unable to understand the nature, scope, and possible consequences of the study.

 Patients unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow up visits, and unlikelihood of completing the study.

['Chronic Obstructive Pulmonary Disease (COPD)']


A Study on the Effects of Ranolazine on Exercise Duration in Subjects With Chronic Stable Angina and Coronary Artery Disease (CAD) With Type 2 Diabetes Mellitus (T2DM)

Summary: This study will evaluate the efficacy of ranolazine compared to placebo on duration of exercise assessed by exercise tolerance testing (ETT) at anticipated peak ranolazine plasma concentration after 12 weeks of treatment in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM).
Inclusion criteria: inclusion criteria:

 Written informed consent

 Males and females aged 18 to 79 years

 Able to perform a Sheffield Modified Bruce Treadmill Exercise Protocol

 At least a 3-months history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin

 Coronary artery disease documented by one or more of the following:

 Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries

 History of myocardial infarction (MI) documented by positive CK-MB enzymes, troponins, or ECG changes

 Cardiac nuclear scan studies diagnostic of CAD, e.g., thallium scan or ECHO with stress or pharmacologic interventions (adenosine, dipyridamole, etc.)

 Stable treatment with one of the following antianginal medications for at least 4 weeks prior to Screening:

 beta-blocker (atenolol up to 50 mg daily or metoprolol up to 100 mg daily)

 dihydropyridine calcium-channel blocker (amlodipine up to 5 mg daily or nifedipine up to 30 mg daily)

 non-dihydropyridine calcium-channel blocker (diltiazem 180 to 360 mg daily or verapamil 180 to 360 mg daily)

 Willingness to discontinue other antianginals and be treated with one of the allowed antianginal therapies

 Documented history of type 2 diabetes mellitus

 Females of childbearing potential must agree to utilize highly effective contraception methods from Screening throughout the duration of study treatment and for 14 days following the last dose of study drug.

Exclusion criteria: :

 Inability to exercise or having exercise limitation due to other co-morbidities that may interfere with ability to perform required ETT (e.g., morbid obesity, significant chronic lung disease, prior hospitalization for acute exacerbation of chronic lung disease or home oxygen use, chronic oral steroid therapy that can limit exercise capacity, osteoarthritis, peripheral artery disease, etc.)

 Any absolute contraindication to ETT

 Presence of electrocardiographic or other abnormalities that interfere with ECG interpretation or may cause a false positive stress test (e.g., ≥ 1 mm horizontal or down-sloping ST segment depression at rest in any standard ECG lead, Lown-Ganong-Levine syndrome, Wolff-Parkinson-White syndrome, left bundle branch block, left ventricular hypertrophy with repolarization abnormality, ventricular pacemaker, etc.)

 Decompensated heart failure

 Clinically significant valvular heart disease or congenital cardiac defects

 Acute coronary syndrome in the prior 2 months or coronary revascularization within the prior 6 months or planned coronary revascularization during the study period

 Stroke or transient ischemic attack within 6 months prior to Screening

 History of serious ventricular dysrhythmias or a history of life-threatening ventricular arrhythmia

 Atrial fibrillation

 QTc > 0.5 seconds

 Hypertrophic cardiomyopathy

 Uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)

 Systolic blood pressure < 90 mm Hg

 Inability to discontinue current antianginal medications and remain on one allowed antianginal therapy

 Clinically significant hepatic impairment

 Creatinine clearance (CLCr) < 30 ml/min

 Prior treatment with ranolazine

 Participation in another investigational drug or device study within 1 month prior to Screening

 Females who are breastfeeding

 Positive serum pregnancy test

 Current treatment with potent inhibitors of CYP3A (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)

 Current treatment with CYP3A and P glycoprotein (Pgp) inducers (e.g., rifampicin/rifampin, carbamazepine, St. John's wort)

 History of illicit drug use or alcohol abuse within one year of screening

 Any other conditions that, in the opinion of the investigator, are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study

['Type 2 Diabetes Mellitus', 'Angina Pectoris', 'Coronary Artery Disease']

Type 2 Diabetes Mellitus
Angina Pectoris
Coronary Artery Disease


Exisulind in Preventing Polyps in Patients With Familial Adenomatous Polyposis

Summary: RATIONALE: Exisulind may be effective in preventing the development and growth of polyps in patients who have familial adenomatous polyposis.~PURPOSE: Randomized phase II/III trial to determine the effectiveness of exisulind in preventing the development and growth of polyps in patients who have familial adenomatous polyposis.
Inclusion criteria: DISEASE CHARACTERISTICS:

 One of the following diagnosis:

 Diagnosis of familial adenomatous polyposis

 Prior total or subtotal colectomy

 Attenuated adenomatous polyposis coli

 May have colon intact

 10-40 duodenal polyps from second portion to 10 cm distal to papilla of Vater

 PATIENT CHARACTERISTICS:

 Age:

 18 to 80

 Performance status:

 Not specified

 Life expectancy:

 Not specified

 Hematopoietic:

 Hemoglobin at least 10 g/dL

 Platelet count at least 100,000/mm^3

 No active hematologic disease

 Hepatic:

 AST and ALT less than 1.5 times upper limit of normal (ULN)

 Alkaline phosphatase less than 1.5 times ULN

 No active hepatic disease

 Renal:

 Creatinine less than 1.5 mg/dL

 No active renal disease

 Other:

 Not pregnant or nursing

 Negative pregnancy test

 Fertile patients must use effective contraception

 No active peptic ulcer disease

 No serious underlying medical or psychiatric illness that would preclude completion of the study or limit survival

 No prisoners or institutionalized patients

 No known allergy to sulindac or related compounds

 No active internal malignancy within the past 5 years

 No alcohol or drug abuse within the past 5 years

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 Not specified

 Chemotherapy:

 Not specified

 Endocrine therapy:

 Not specified

 Radiotherapy:

 Not specified

 Surgery:

 See Disease Characteristics

 Other:

 No prior non-steroidal anti-inflammatory drugs (NSAIDs) or salicylates more than 10 days a month for the past 3 months

 No concurrent NSAIDs (e.g., mesalamine, olsalazine, azodisalicylate, salsalate, sulfasalazine)

 Aspirin for cardiac reasons allowed (81 mg/day or 325 mg twice/week)
Exclusion criteria:

['Colorectal Cancer', 'Small Intestine Cancer']

Colorectal Cancer
Small Intestine Cancer


Microarchitecture, Bone Strength and Fracture Risk in Type 2 Diabetes

Summary: This multicenter, prospective, observational cohort study will assess bone differences in women and men with type 2 diabetes mellitus (T2DM) with and without fragility fractures.
Inclusion criteria: inclusion criteria:

 - presence of type 2 diabetes for at least 3 years (history of treatment for type 2 diabetes)

Exclusion criteria: :

 immobility

 coexisting metabolic bone disease or comorbidities affecting bone health

 previous treatment with osteoporosis medication or intake of medications known to affect bone metabolism (e.g. steroids) within 6 months prior to enrolment

 thiazolidinedione use

['Type 2 Diabetes Mellitus', 'Bone Fractures']


Forteo Trial on Idiopathic Osteoporosis in Premenopausal Women

Summary: Idiopathic osteoporosis (IOP) is defined as osteoporosis that affects young, otherwise completely healthy individuals with no secondary cause of bone loss. In the course of our prior research with premenopausal women with IOP, the investigators have shown that women with IOP have low areal bone mineral density (aBMD) at the spine, hip and forearm compared to normal women. Additionally, using noninvasive high resolution imaging of the central and peripheral skeleton and detailed analyses of transiliac crest bone biopsies, the investigators identified several features of bone quality in premenopausal women with IOP.~There is currently no FDA-approved therapy for IOP in premenopausal women. However, teriparatide (Forteo) has been shown to improve bone mass and microarchitecture in postmenopausal women and is approved for men with primary or idiopathic osteoporosis, as well as men, premenopausal and postmenopausal women with glucocorticoid-induced osteoporosis. Because IOP in premenopausal women is an orphan disease, with an estimated prevalence of about 113,000 in the United States, pharmaceutical companies are unlikely to support development of therapies for this indication. Therefore, the major objective of this protocol is to establish the safety and efficacy of teriparatide in premenopausal women with IOP in a phase 2 clinical trial. All subjects will receive teriparatide as part of the study, but a randomly selected group of patients (10) will receive one year of placebo injections first before starting their two years of treatment. The remainder of subjects (30) will receive active drug only for two years.~Funding Source - FDA OOPD
Inclusion criteria: inclusion criteria:

 Premenopausal women, aged 20-45, with regular menses and no historical or biochemical secondary cause of osteoporosis.

 Documented adult fractures judged to be low-trauma.

 Must be willing to use effective contraception throughout the period of study drug administration.

 inclusion criteria - vary slightly based on age category:

 Premenopausal women ages 20-35 years must have at least one major osteoporotic fracture (excluding fractures of fingers, toes and face) and low Bone Mineral Density (BMD).

 Premenopausal women above the age of 35 years should have a history of fracture and/or low BMD.

Exclusion criteria: :

 History of any condition that increases the risk of osteosarcoma

 Early follicular phase serum

 Disorders of mineral metabolism

 Suspicion of osteomalacia

 Vitamin D deficiency

 Pregnancy or lactation within past 12 months

 Prolonged amenorrhea (> 6 months) during reproductive years (except pregnancy or lactation)

 Prior eating disorder

 Malignancy, except cured basal or squamous cell skin carcinoma

 Endocrinopathy: new onset untreated hyperthyroidism, hypothyroidism, Cushing's syndrome, prolactinoma

 Renal insufficiency

 Liver disease

 Intestinal disorders

 History/current glucocorticoids (GCs), anticonvulsants, anticoagulants, methotrexate, depot progesterone, Gonadotrophin-releasing hormone (GnRH) agonists

 Oral glucocorticoid use (subject will not be excluded if used dose equivalent to less than prednisone 5 mg for <3 months).

 Current anticoagulant use or low molecular weight

 Depo Provera use (subjects will not be excluded if used at age>20, >5 years ago)

 Drugs for osteoporosis (raloxifene, bisphosphonates, denosumab, calcitonin, TPTD). Subjects who discontinue these medications will be eligible 3 months after stopping raloxifene or calcitonin, 12 months after stopping alendronate, risedronate, ibandronate, or pamidronate and 18 months after stopping denosumab. Subjects with prior use of zoledronate may be eligible if received only one dose >4 years ago. Total bisphosphonate exposure must be < 1 year. Subjects who have taken TPTD in the past will not be eligible unless used for <3 months, > 2 years ago.

['Adult Idiopathic Generalized Osteoporosis']


Rituximab in Rheumatoid Arthritis Lung Disease

Summary: This study will examine the course of patients with progressive rheumatoid arthritis associated interstitial lung disease (RA-ILD) treated with rituximab for safety and progression-free survival at 48 weeks. Safety of rituximab therapy in this disease will be assessed through patient history, physical exams and laboratory parameters.~Twelve male/or female patient with RA-associated lung disease (6 of each nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) histological subtype) will be enrolled~The study involves 12 visits over 48 weeks~Rituximab will be administered intravenously at Day 1 and Day 15 with repeat dosing at six months.
Inclusion criteria: inclusion criteria:

 Diagnosis of RA according to the revised 1987 American Rheumatism Association criteria

 Absence of clinical features suggesting infection, neoplasm, sarcoidosis, interstitial lung disease other than UIP or NSIP, other collagen vascular disease, or exposure to known fibrogenic drugs or environmental factors

 Diagnosis of progressive interstitial pneumonia of UIP or NSIP subtype, based on the following criteria

 Clinical symptoms consistent with interstitial lung disease with onset between 3 months and 36 months prior to screening.

 Worsening as demonstrated by any one of the following within the past year:

 > 10% decrease in Forced Vital Capacity (FVC)

 increasing infiltrates on chest X-ray or High Resolution Computed Tomography (HRCT), or worsening dyspnea at rest or on exertion

 Diagnosis of UIP or NSIP by either of the following:

 Open or video-assisted thoracic surgery (VATS) lung biopsy showing definite or probable UIP or NSIP

 HRCT scan showing definite or probable UIP or NSIP AND abnormal pulmonary function tests (reduced FVC or decreased diffusing capacity of carbon monoxide (DLco) or impaired gas exchange at rest or with exercise) AND insidious onset of otherwise unexplained dyspnea or exertion and bibasilar, inspiratory crackles on auscultation

 FVC > 50% of predicted value at Screening

 DLco >30% of predicted value at Screening

 5. No change of disease-modifying anti-rheumatic drug (DMARD) treatment within the last 3 months

Exclusion criteria: :

 History of clinically significant environmental or drug exposure known to cause pulmonary fibrosis.

 Forced expiratory volume in one second (FEV1) FEV1/FVC ratio < 0.6 at screening (pre- or post-bronchodilator).

 Residual volume > 120% predicted at Screening

 Evidence of active infection

 Any pulmonary condition other than UIP/NSIP, which, in the opinion of the site principal investigator, is likely to result in the death of the patient within the next year

 History of unstable or deteriorating cardiac or neurologic disease

 Pregnancy or lactation

 Treatment with cyclophosphamide, cyclosporine, interferon gamma or beta, anti-tumor necrosis factor therapy, anti-interleukin 1 (IL1) therapy or with endothelin receptor blockers within the last 8 weeks; experimental therapy for rheumatoid arthritis

 Creatinine > 1.5 X upper limit of normal range (ULN) at Screening

 Hematology outside of specified limits: white blood cell (WBC) < 2,500/mm^3 or absolute neutrophil count (ANC) < 1500

 Hematocrit < 27% or > 59%, platelets < 100,000/mm^3 at screening

 Positive hepatitis B or C serology

 Any medical condition, which in the opinion of the site principal investigator, may be adversely affected by the participation in this study

 History of recurrent significant infection or history of recurrent bacterial infections

 Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening

 Abnormal neurological examination reflective of central nervous disease, including paresis, cognitive impairment and problems with coordination

 Current enrollment in another clinical trial

 Fever (>99.5º F)

 History of previous rituximab administration

 Receipt of any vaccine, particularly live viral vaccines, within 4 weeks of first study dose

 Decreased Immunoglobulin G (IgG) and Immunoglobulin M (IgM) levels (below lower limit of normal range)

 Present or past malignancy

 History of severe allergic or anaphylactic reaction to administration of humanized or murine monoclonal antibodies

 Positive human immunodeficiency virus (HIV) serology

['Rheumatoid Arthritis', 'Interstitial Pneumonia']

Rheumatoid Arthritis
Interstitial Pneumonia


Chest Imaging, Breath, and Biomarkers in a Screening Trial

Summary: The investigators would like to see if lung cancer screening with chest x-rays,computer aided detection (CAD)and a lose dose CT scan can detect lung cancer in early stages when it is more responsive to treatment. The investigators would also like to see if early detection will reduce the incidence of symptomatic advanced lung cancer compared to no screening in former and current smokers with or without a family history of lung cancer who are 40-75 years old.
Inclusion criteria: inclusion criteria:

 ages 40-75 years

 If ages 40-59, then one of the following criteria needs to be met:

 Current or ex-smoker with >25 pack years and a family history of lung cancer(parent or sibling) OR

 current or ex-smoker with > 25 pack years and COPD OR

 current or ex-smoker with a > 35 pack year history

 If ages 60-75, then one of the following additional criteria needs to be met:

 Current or ex-smoker with >25 pack years and a family history of lung cancer (parent or sibling) OR

 Current or ex-smoker with >25 pack years and COPD OR

 Current or ex-smoker with a >30 pack year history

 Subject is able to return to Cleveland Clinic for annual follow-up screening

 Subject is willing to sign a medical release form

Exclusion criteria: :

 Current health requires oxygen

 Have had a chest x-ray or CT of the chest within the last 6 months

 Previous pneumonectomy

 Lobectomy of the lung within the last 5 years

 Diagnosed malignancy within the last 5 years, excluding non-melanoma skin cancer, carcinoma in situ of the cervix and localized prostate cancer

 A medical condition that would prevent treatment for lung cancer

 Within the last 6 weeks, one of the following has occured:

 A new cough or chronic cough that has gotten worse

 Either new shortness of breath, or any worsening of shortness of breath

 A cough producing blood

 Constant chest pain

 Respiratory infection, pneumonia, or cold

 Unintentional and unexplained weight loss greater than 5% of total body weight

['chest x-ray with or without CAD, lose dose CT scan']

chest x-ray with or without CAD
lose dose CT scan


Preventing the Development of Venous Insufficiency in Pregnant Women Through Use of Compression Stockings

Summary: Problem: Approximately 4 million live births occur in the United States each year. Pregnancy causes many physical changes in the mother, including venous distension, increased ability to form blood clots, and hormonal changes. Data suggest that these factors help cause venous insufficiency (when the veins do not adequately return blood from the extremities to the torso). As venous insufficiency progresses, complications follow, the most severe of which include superficial thrombophlebitis and deep venous thrombosis (DVT, or blood clots). Although the fear of DVT has been well publicized, its prevention and prevalence in pregnant women has not been well-studied.~The exact cause of venous insufficiency is not known. However, known risk factors include being female and hormonal changes associated with oral contraceptive use, certain hormone replacement medications, and pregnancy. Being pregnant places the mother at additional risk for developing venous insufficiency.~Compression stockings are used to manage the condition, but this is by no means standard of care despite their easy use and safety. The medical community's understanding of how compression stockings work is largely theoretical; however, it is believed that the compression works by preventing venous hypertension in the lower legs, thereby preventing venous insufficiency and its associated complications.~Research hypothesis: The investigators hypothesize that compression stocking use will be associated with lower incidence of varicose veins and, in those patients who already have varicose veins, lower incidence of complications associated with venous insufficiency. Further, the investigators believe that compression stocking use will be associated with a lower incidence or lessening of symptoms associated with venous insufficiency.~Importance: An undetected DVT can be fatal. Even if detected promptly, DVT is associated with long term health problems. Treatment of a DVT requires anticoagulation which can be risky to both mother and fetus. The prevention or reduction of DVT in pregnant women through use of compression stockings would revolutionize their care. Further, this intervention is safe and noninvasive.~The investigators propose to conduct a randomized, pilot study comparing pregnant women without and with varicose veins randomized to wear compression stockings to a similar group of participants randomized to no compression stocking use.
Inclusion criteria: inclusion criteria:

 Pregnant women 18-45 years of age.

 Fetal gestation between 8-20 weeks.

 Patient is seeking care for the pregnancy at one of the study locations (Johns Hopkins East Baltimore Campus, Johns Hopkins Bayview Medical Center, and Johns Hopkins at White Marsh).

 Ability to complete informed consent and willingness to comply with protocol (return for all follow-up visits & participate in phone interviews).

Exclusion criteria: :

 Inability to wear compression stockings.

 Women who currently have been prescribed to wear compression stockings by a medical professional.

 Chronic dermatological condition (i.e. psoriasis).

 Chronic deep vein thrombus or chronic phlebitis.

 In women with varicose veins: Presence of primary outcome (superficial thrombophlebitis or DVT) on first visit ultrasound.


Evaluation of Adhexil Safety and Efficacy in Prevention and/or Reduction of Adhesions in Gynecological Surgery

Summary: The objective of this study is to evaluate the safety and efficacy of ADHEXIL™ in preventing and/or reducing post-operative adhesions in patients undergoing surgery involving the ovaries.
Inclusion criteria: inclusion criteria:

 Female patients aged 18-45 years at screening.

 Patients undergoing elective laparoscopic surgery involving at least one adnexa.

Exclusion criteria: :

 Pregnant (including ectopic pregnancy) or breastfeeding patient.

 Patients with a documented diagnosis of cancer.

 Patients with a lymphatic, hematologic or coagulation disorder.

 Patients with a known or suspected hypersensitivity to blood, blood products or any constituent of Adhexil™.

 Patients who are immunocompromised, possess autoimmune disorders, or who are routinely taking anticoagulants.

 Patients who have participated in another clinical study within 30 days of enrolment.

 Investigator's opinion that the patient is medically unfit or would be at major risk if enrolled into the study.

['Ovarian Cysts', 'Endometriosis', 'Adhesions']


Narrow Band Imaging in Flexible Cystocopy

Summary: Patients with first time hematuria or patients previously diagnosed with papillomas/CIS of the bladder are included in the study. All surgeons are highly experienced in WL cystoscopy and familiar with NBI findings. Cystoscopy is performed with HD cameras and Olympus light sources.~First, a systematic cystoscopy is made in WL. Secondly, the clinical decision is noted. After WL, the cystoscopy is made with NBI and any potential subsequent change in the clinical decision is noted.~A total number of 896 patients is planned to be included.
Inclusion criteria: inclusion criteria:

 Patients undergoing flexible cystoscopy because of haematuria or previous NMIBC

Exclusion criteria: :

 Patients not fullfilling the above

['Narrow Band Imaging in Flexible Cystoscopy']


Recognition and Early Intervention on Prodrome in Bipolar Disorders

Summary: Background and study hypothesis:~Many studies including prospective studies have been demonstrated that a long symptomatic prodromal phase exists prior to the onset of full-brown bipolar disorder, lasting for 9-12 years (Egeland et al., 2000). During the prodromal stage, there are three main clusters of syndromes, including hypomania/mania symptoms, depressive symptoms, and signs of attention deficit hyperactivity disorders (Correll et al., 2007; Tillman et al., 2003; Mantere et al., 2008). Of the hypomania/mania symptoms, decreased sleep, elevated mood, irritability, mood lability, increased energy, and psychomotor agitation are present most frequently. The prodromal depressive symptoms are reported to be depressed mood, anhedonia, insomnia, feelings of worthlessness. Among patients with bipolar disorders, 22.5% reported to comorbid with pediatric ADHD. In addition, some symptoms are considered as non-specific such as decreased functioning, anger outburst, social isolation, and anxiety (Egeland et al., 2000).~Offspring of parents with bipolar disorders are much likely to present prodromal symptoms compared to offspring of healthy parents. In a 10-year longitudinal study using 55 prodromal symptoms checklist, , Egeland et al.(2002) found that 38% offspring of parents with bipolar disorder were considered as at risk compared to 17% in children of healthy parents. In a 15-year follow-up study, Duffy et al.,(2009) found that 32.7% offspring (aged 8-25 years old) of parents with bipolar disorder met the criteria of major mood episode.~Objectives:~One primary objective of this study is to prospectively identify the prodromal stage of bipolar disorder.~Another primary objective is to conduct a randomized, place-controlled trial of aerobic exercise on people who suffering from prodromal symptoms to the extent of significantly impaired function, with attempt at delaying or preventing the onset of a full-blown bipolar disorder.~Design of study and the procedures:~The study will consist of two phases: one-week screening period and a randomized, placebo-controlled, 3-month trial. During the screening period, offspring of parents with bipolar disorder will undergo systematically clinical evaluations. The offspring will be evaluated with clinical symptoms assessing scales, neuropsychological tests, magnetic resonance imaging. During the 3-month trial period, the offspring who meet the inclusion criteria will be randomly assigned to receive treatment of aerobic exercise, placebo, or wait-list group. Psychiatrists are scheduled to assess mood, treatment outcome during the 3-month trial.~Subjects and treatment It is expected that 120 offspring of parents with bipolar disorder aged between 10-25 years, meeting the inclusion of prodromal stage, will be included in the study. All of the offspring will undertake the Kiddie Sads Present and Lifetime Version (K-SADS-PL), and a 70 checklist items of potential prodromal symptoms suggest by us as well as by Dr. Correll et al. (2007). The parents of these offspring are to have a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders)-defined bipolar disorder (bipolar I or II), confirmed by the Chinese version of Structured Clinical interview for DSM-IV-TR Axis I Disorders patient edition (SCID-I/P) [First et al., 2002]. The offspring are to be recruited through the referrals by their parents who will receive psychiatric services in the Guangzhou psychiatric Hospital.~The offspring will be randomly assigned to aerobic exercise and placebo controlled groups. The aerobic exercise would include cycling, jogging,table tennis, and playing badminton for 40 mins at least 3 times a week for 3 months. In each exercise, participants are supposed to exercise to the extent of getting sweaty. In the placebo group, participants will receive general psychoeducation, including delivering knowledge on symptoms, discussion of the suffering mental difficulties, and general coping techniques.~Significance:~Bipolar disorder is a common, chronic, and recurrent mental disorder. The recognition of prodromal stage of bipolar disorder and the early intervention on it may help delay or prevent the onset of bipolar disorder.
Inclusion criteria: inclusion criteria:

 have at least one biological parent diagnosed as bipolar disorder (bipolar I or II)

 have at least one of the following syndromes i) two or more DSM-IV defined hypomania/mania symptoms, lasting for at least 4 days; ii) two or more DSM defined major depressive symptoms, lasting for 1 week; iii) at least one of the psychotic symptoms, lasting at least 10 min for each manifestation, and 2-7 manifestations a week for at least 3 months, including: ideas of reference; odd ideas, odd belief, unusual perceptual experiences, bizarre thought or speech, Grandiosity, suspicious ideas, paranoid idea, odd mannerisms, hallucination, disorganized/catatonic behavior; iv)two or more of the DSM-IV defined Attention deficit hyperactivity disorder (ADHD)symptoms; and there must be clear evidence of clinically significant impairment in social, academic, or occupational functioning due to ADHD symptoms

Exclusion criteria: :

 DSM-IV defined Axis I disorders;

 Serious general medical illness;

 mental retardation;

 was/is treated with antipsychotic drugs;

 unable to complete neuropsychological tests due to physical conditions;

 in pregnancy and lactation;

 was taking thyroxine therapy in the last three months or is taking hormone therapy


Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

Summary: This phase II trial studies how well iodine I-131 works with or without selumetinib in treating patients with thyroid cancer that has returned (recurrent) or has spread from where it started to other places in the body (metastatic). Many thyroid cancers absorb iodine. Due to this, doctors often give radioactive iodine (iodine I-131) alone to treat thyroid cancer as part of standard practice. It is thought that the more thyroid tumors are able to absorb radioactive iodine, the more likely it is that the radioactive iodine will cause those tumors to shrink. Selumetinib may help radioactive iodine work better in patients whose tumors still absorb radioactive iodine. It is not yet known whether iodine I-131 is more effective with or without selumetinib in treating thyroid cancer.
Inclusion criteria: inclusion criteria:

 Diagnosis of recurrent and/or metastatic thyroid cancer

 Histological or cytological confirmation of thyroid carcinoma of follicular origin (including papillary, follicular, or poorly differentiated subtypes and their respective variants); NOTE: medullary and anaplastic thyroid cancers are excluded; Hurthle cell carcinomas are excluded (defined as having an invasive tumor composed of > 75% oncocytic [Hurthle] cells lacking the nuclear features of papillary carcinoma, tumor necrosis, and marked mitotic activity); patients with oncocytic (Hurthle cell) variants of papillary thyroid carcinoma (defined as a tumor composed of a majority of oncocytic [Hurthle] cells having the nuclear features of papillary carcinoma) are eligible to participate

 RAI-avid lesion on a radioiodine scan (a diagnostic, post-therapy, or post-ablation scans) performed =< 24 months prior to registration, which suggests that therapy with 131I is justifiable in the judgment of the investigator

 Clinically or radiographically evident structural disease; patients with measurable disease and those with only non-measurable (non-target) structural disease (according to modified Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1 criteria) are eligible;

 NOTE 1: Modification of the RECIST v1.1 measurable disease criteria includes a change in the definition of what is considered a measurable malignant lymph node; a malignant lymph node is considered measurable if any of the following apply:

 It is noted to be RAI-avid on radioactive iodine imaging (diagnostic or post-therapy whole body scans acceptable) and it measures >= 1 cm in the long axis,

 It is pathologically proven to be involved with thyroid cancer (by cytology or pathology) and it measures >= 1 cm in the long axis, or

 Its short axis is >= 1.5 cm when assessed by computed tomography (CT) scan NOTE 2: Patients only with biochemical evidence of disease without structural evidence of cancer are not eligible for this study

 For patients with non-measurable, structural disease the following must apply:

 Undetectable thyroglobulin antibody AND

 A serum thyroglobulin of 10 ng/ml or greater in the context of suppressed thyroid-stimulating hormone (TSH) (TSH =< 0.4 mcU/ml) =< 28 days prior to study registration; use of any thyroglobulin assay is allowed, though all serum thyroglobulin measurements for study purposes must be conducted with the same thyroglobulin assay

 Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

 Able to swallow and retain orally-administered medication with no clinically significant gastrointestinal abnormalities that may alter absorption

 Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to randomization)

 Platelet count >= 100,000/mm^3 (obtained =< 28 days prior to randomization)

 Hemoglobin > 9.0 g/dL (obtained =< 28 days prior to randomization)

 Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 28 days prior to randomization)

 Aspartate transaminase (AST) =< 2.5 x ULN (or =< 5 x ULN in presence of liver metastases) (obtained =< 28 days prior to randomization)

 Creatinine =< 1.5 mg/dL OR calculated creatinine clearance of >= 50 ml/min by either the Cockcroft-Gault formula or 24-hours urine collection analysis (obtained =< 28 days prior to randomization)

 Negative pregnancy test performed =< 7 days prior to registration for women of childbearing potential only

 Provide informed written consent

 Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

 Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up

 Willing to provide mandatory archival tumor tissue (block or minimum of 30 unstained slides from a primary or recurrent/metastatic thyroid cancer) for correlative research purposes; NOTE: patients with less archival tumor tissue available may still be eligible for the study after discussion with Academic and Community Cancer Research United (ACCRU); receipt of archival tumor tissue is not required for study registration and initiation of therapy

 Willing to provide mandatory blood samples for correlative research purposes

Exclusion criteria: :

 131I therapy =< 6 months prior to registration; Note: 131I administered solely for diagnostic purposes is not considered 131I therapy

 External beam radiation therapy =< 28 days prior to registration; note: previous treatment with radiation is allowed if the investigator judges it will not compromise patient safety on the study

 Having been treated with a total cumulative (lifetime) 131I therapeutic activity > 800 mCi (excluding 131I activity administered for diagnostic scans)

 Treatment with chemotherapy or targeted therapy (e.g. tyrosine kinase inhibitor) =< 28 days prior to registration

 Prior exposure to mitogen-activated protein kinase kinase (MEK), RAS, or RAF inhibitors (note: previous exposure to sorafenib is allowed) OR history of hypersensitivity to selumetinib, thyrotropin alpha (Thyrogen), or any excipient agents

 Unresolved toxicity > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 from previous anti-cancer therapy, except for alopecia

 Cardiac conditions as follows:

 Uncontrolled hypertension (blood pressure [BP] >=150/95 mmHg despite medical therapy)

 Left ventricular ejection fraction < 55% measured by echocardiography

 Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest

 Symptomatic heart failure (New York Heart Association [NYHA] grade II-IV)

 Prior or current cardiomyopathy

 Severe valvular heart disease

 Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)

 Acute coronary syndrome =< 6 months prior to registration

 Ophthalmological conditions as follows:

 Intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)

 Current or past history of central serous retinopathy or retinal vein occlusion

 Symptomatic or untreated leptomeningeal disease, brain metastasis, or spinal cord compression

 Unable to follow a low iodine diet or requiring medication with high content in iodide (e.g., amiodarone)

 Received iodinated intravenous contrast within =< 2 months of registration; avoidance of iodinated oral contrast is also preferred but not strictly required for study enrollment; NOTE: those who have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that excess iodine has been cleared (defined as urinary iodine documented to be < 300 mcg/day by either a spot urinary iodine or 24-hour urinary iodine measurement)

 Any of the following:

 Pregnant women

 Nursing women

 Men or women of childbearing potential who are unwilling to employ adequate contraception

 Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

 Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

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

 Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm. (NOTE: Performance of investigational 124I PET/CT scans is allowed prior to and during conduct of this study)

 Other active malignancy =< 2 years prior to registration that will interfere with conduct of this trial; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, patients must not be receiving other specific treatment (chemotherapy, hormonal therapy, radiation) for their cancer

 Not willing to discontinue use of supplemental vitamin E

['Iodine I-131', 'Placebo Administration', 'Selumetinib']

Iodine I-131
Placebo Administration
Selumetinib

['Metastatic Thyroid Gland Carcinoma', 'Poorly Differentiated Thyroid Gland Carcinoma', 'Recurrent Thyroid Gland Carcinoma', 'Stage IV Thyroid Gland Follicular Carcinoma AJCC v7', 'Stage IV Thyroid Gland Papillary Carcinoma AJCC v7', 'Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7', 'Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7', 'Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7', 'Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7', 'Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7', 'Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7']