PTHrP and Osteoporosis

Summary: PTH-related protein, or ''PTHrP'', is a hormone which was discovered in 1987. As its name implies, it is closely related to another hormone discovered in the 1920's named parathyroid hormone or ''PTH''. PTH has been shown to be effective in treating osteoporosis in both animals and humans. PTHrP has been shown to be effective in treating osteoporosis in laboratory animals, and there are strong scientific reasons to think that it may be effective in humans as well. However, no human trials with PTHrP in the treatment of osteoporosis have been performed. The studies in this trial are focussed on determining whether PTHrP can indeed increase bone mass in postmenopausal women with osteoporosis, when administered daily by subcutaneous injection for three months.
Inclusion criteria: inclusion criteria:

 Healthy caucasian postmenopausal females between 50-75 years of age with low bone mineral density at the lumbar spine or hip as measured using dual energy x-ray absorptiometry or DXA.

 ON estrogen replacement treatment for at least three years.

Exclusion criteria: :

 Heart, vascular, kidney, liver, lung, hormonal, musculo-skeletal disease (other than osteoporosis), rheumatic, blood diseases are

Parathyroid hormone-related protein or ''PTHrP''


Efficacy and Safety of Lacidipine in Chronic Stable Angina

Summary: The aim of this study was to explore whether lacidipine at doses of 2 mg, 4 mg and 6 mg decreased the symptoms of angina, compared to placebo in patients with chronic stable angina
Inclusion criteria: inclusion criteria:

 Age 18 to 80 years

 History of stable, exertional angina pectoris (Canadian Cardiovascular Society functional class II to III) for at least 3 months duration prior to enrolment in the study

 Patients not currently receiving treatment with antianginal medication (other than short-acting nitrates)

 Between visits 2 and 3 two treadmill exercise tests, demonstrating ≥ 0.1 mV of horizontal or down sloping ST-segment depression, must be carried out. The difference in symptom-limited exercise duration between these two tests must not exceed 20%

 Total treadmill exercise duration > 3 minutes (i.e. stage 2 or above on a standard Bruce protocol)

 Coronary artery disease, preferably (not mandatory) documented by a history of proven myocardial infarction and/or coronary angiography indicating ≥ 50% reduction in luminal diameter of one or more coronary arteries or their primary branches

Exclusion criteria: :

 Myocardial infarction within 3 months prior to enrolment in the study

 Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery within 6 months

 Other types of angina (variant, unstable)

 Uncontrolled hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg)

 Resting heart rate < 50 bpm or > 100 bpm

 Significant valvular heart disease

 Heart failure New York Heart Association Class III or IV

 Chronic obstructive pulmonary disease and/or asthma with clinical symptoms requiring regular medication

 Significant arrhythmia (since this may interfere with the interpretation of the electrocardiogram) including Wolff Parkinson-White syndrome, atrial fibrillation, atrial flutter, sick sinus syndrome, significant Atrio-Ventricular heart block, intraventricular conduction defect (QRS > 0.12 seconds) ventricular pre-excitation, bundle branch block, the presence of a pace-maker, the presence of an implanted automatic defibrillator, uncorrected hypokalaemia (potassium < 3.5 mmol/litre)

 Insulin dependent diabetes mellitus

 Significant liver disease (Aspartate Aminotransferase or Alanine Aminotransferase > twice the upper limit of reference range)

 Significant renal disease (creatinine > 1.5 x upper limit of reference range)

 Any clinical condition which in the opinion of the investigator, would preclude the safe fulfilment of the protocol and the safe administration of trial medication

 Inability to perform repeated exercise testing due to extra-cardiac reasons

 Concomitant treatment with any other anti-anginal medication, whether or not prescribed for this indication (e.g. calcium channel blockers, β-blockers or long-acting nitrates)

 Concomitant treatment with anti-arrhythmic medication, digitalis or tricyclic anti-depressants or other agents known to affect ST-segment morphology

 Known hypersensitivity to any of the components of the investigational drug

 Pregnant or nursing women or women of child bearing potential

 Participation in any other clinical trial within 2 months of enrolment

 History of drug or alcohol abuse

['Lacidipine, low dose', 'Lacidipine, medium dose', 'Lacidipine, high dose', 'Placebo']

Lacidipine
low dose
Lacidipine
medium dose
Lacidipine
high dose
Placebo


Effects of Two Anti-HIV Drug Regimens on HIV Transmission Risk Behavior Among SMART Study Participants

Summary: The purpose of this study is to compare the effects of two different anti-HIV drug regimens on HIV transmission risk behavior among SMART study participants.
Inclusion criteria: inclusion criteria:

 Coenrollment in the SMART study

 Parent or guardian willing to provide informed consent, if applicable
Exclusion criteria:


Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese(MEGA Study)

Summary: To evaluate the primary preventive effect of low-dose pravastatin against coronary heart disease (CHD) in Japanese hypercholesterolemic patients.
Inclusion criteria: inclusion criteria:

 TC:220～270mg/dl

 Male: 40-70 years old/ female: postmenopausal-70 years old

 <40kg in weight

Exclusion criteria: :

 FH

 History of CHD(angina, MI, post-PTCA/CABG, etc.)

 History of CVA(stroke, TIA, etc.)

 Underlying malignant tumor


Safe Implementation of Thrombolysis in Stroke - Monitoring Study

Summary: Study to evaluate the safety and efficacy of intravenous alteplase within 3 hours of symptom onset in acute ischemic stroke patients
Inclusion criteria: inclusion criteria:

 Female or male in-patient

 Age 18 - 80 years

 Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition, gaze, vision and/or neglect. Ischemic stroke is defined as an event characterized by sudden onset of acute focal neurological deficit, presumed to be caused by cerebral ischemia, after CT scan exclusion of hemorrhage

 Onset of symptoms within 3 hours prior to initiation of thrombolysis treatment

 Stroke symptoms present for at least 30 minutes that had not significantly improved before treatment. Symptoms must be distinguishable from an episode of generalized ischemia (i.e. syncope), seizure, or migraine disorder

 Patients are willing to receive thrombolysis treatment and to give informed consent with regard to retrieval of data and follow up procedures, according to the regulations in participating countries

 Willingness and ability to comply with the study protocol

Exclusion criteria: :

 Evidence of intracranial hemorrhage (ICH) on the CT-scan

 Symptoms of ischemic attack began more than 3 hours prior to infusion start or when time of symptom onset is unknown

 Minor neurological deficit or symptoms rapidly improving before start of infusion

 Severe stroke as assessed clinically and/or by appropriate imaging techniques

 Seizure at onset of stroke

 Symptoms suggestive of subarachnoid hemorrhage, even if the CT-scan is normal

 Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory

 Patients with any history of prior stroke and concomitant diabetes

 Prior stroke within the last 3 months

 Platelet count of below 100,000/mm³

 Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, or aggressive management (IV medication) necessary to reduce BP to these limits

 Blood glucose <50 or > 400 mg/dl

 Known hemorrhagic diathesis

 Patients receiving oral anticoagulants, e.g. warfarin sodium

 Manifest or recent severe or dangerous bleeding

 Known history of or suspected intracranial hemorrhage

 Suspected subarachnoid hemorrhage or condition after subarachnoid hemorrhage from aneurysm

 Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)

 Hemorrhagic retinopathy, e.g. in diabetes (vision disturbances may indicate hemorrhagic retinopathy)

 Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture

 Bacterial endocarditis, pericarditis

 Acute pancreatitis

 Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial- aneurysm, arterial/venous malformation

 Neoplasm with increased bleeding risk

 Severe liver disease, including hepatic failure, cirrhosis, portal hypertension oesophageal varices) and active hepatitis

 Major surgery or significant trauma in past 3 months

 All in- and


Desiccated Thyroid Extract and Levothyroxine for Hypothyroidism Treatment

Summary: Our hypothesis is that hypothyroid patients on DTE may have a decrease in symptoms, an improvement of cognitive function, and an increase in sense of well-being/ quality of life equivalently compared with L-T4.
Inclusion criteria: inclusion criteria:

 Patients will be between the ages of 18 to 65 and will have been on levothyroxine for primary hypothyroidism for at least 6 months.

Exclusion criteria: :

 Patients will be excluded if they have the following problems: pregnancy, plan for pregnancy in the next 12 months, cardiac disease, especially coronary artery disease, chronic obstructive lung disease, malabsorption disorder, gastrointestinal surgeries, significant renal or liver dysfunction, seizure disorders, thyroid and non-thyroid active cancers, uncontrolled psychosis, psychotropic medication use, steroid use, amiodarone, chemotherapy for cancer, iron supplement more than 325mg per day, carafate/ proton pump inhibitor use, cholestyramine use, and those with recent PCS orders who are expected to move out of the geographic area, age less than 18 years old or older than 65 years old.

 Patients scheduled for deployment will be excluded.

['Levothyroxine', 'Desiccated thyroid extract']

Levothyroxine
Desiccated thyroid extract


Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome

Summary: Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary disorder predisposing for colorectal cancer. To reduce the risk of colorectal cancer, patients undergo colonoscopy every 1-2 years. Chromoendoscopy is relatively new technique which improves the detection of adenomas, the precursor lesions of colorectal cancer. The aim of this study is to determine whether chromoendoscopy, including polypectomy of all detected lesions, reduces the development of colorectal neoplasia and the need for colectomy in LS patients.
Inclusion criteria: inclusion criteria:

 proven carrier of a MLH1, MSH2 or MSH6 mutation

 age between 20 and 70 years

 written informed consent

Exclusion criteria: :

 previous large bowel surgery

 psychological/physical conditions hampering compliance with the study protocol


Follow-up Study of GSK Biologicals' Human Papilloma Virus (HPV) Vaccine to Prevent Cervical Infection in Young Adults

Summary: Human Papilloma virus (HPV) are viruses that cause a common infection of the skin and genitals in men and women. Several types of HPV infection are transmitted by sexual activity and, in women, can infect the cervix (part of the uterus or womb). This infection often goes away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. If a woman is not infected by HPV, it is very unlikely that she will get cervical cancer. This is an observer blind follow up study of the study HPV-001, which evaluated the ability of the HPV vaccine to prevent HPV infection. The current study invites all of the 1113 subjects in the HPV-001 study that received all three doses of vaccine/placebo to be enrolled and followed-up for several additional years to see if the HPV vaccine prevents HPV-16 and HPV-18 infections and to evaluate the safety of the vaccine. Subjects will remain in the same study group as in the primary study. No vaccine or placebo will be administered in this study.~The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Inclusion criteria: inclusion criteria:

 Participated in study 580299/001 and received all three doses of vaccine/placebo.

 Written informed consent obtained from the subject prior to enrollment

Exclusion criteria: :

 Decoding of the subject's treatment allocation to either the subject or the investigator in study 580299/001.


Diagnosis of Ventilator- Associated Pneumonia in Children: A Comparative Study of Bronchoscopic and Non-Bronchoscopic Methods

Summary: Background and Objectives: There is a need to validate and suggest easy and less costly diagnostic method for diagnosis of ventilator-associated pneumonia in developing country. The study was performed to compare available methods for the diagnosis and to characterize the organisms causing VAP.~Design and Methods: All patients on mechanical ventilation for more than 48 hours and simplified CPIS ≥ 6 were enrolled prospectively. Four diagnostic procedures, endotracheal aspiration (ETA), blind bronchial sampling (BBS), blind bronchoalveolar lavage (blind BAL) and bronchoscopic BAL (BAL) were performed in same sequence within 12 hours. The bacterial density ≥ 104 cfu/ mL BAL samples were taken as reference standard.
Inclusion criteria: inclusion criteria:

 Children on mechanical ventilation for more than 72 hours and having simplified clinical pulmonary infection score more than 6 were included in study.

Exclusion criteria: :

 Age less than 1 month.


Prognostic Impact of Sleep Apnea on Cardiovascular Morbidity and Mortality, in End Stage Renal Disease Patients

Summary: The purpose of this study is to prospectively evaluate the impact of sleep apnea on the cardiovascular morbidity and mortality of patients with end-stage renal disease.
Inclusion criteria: inclusion criteria:

 end stage renal disease on renal replacement therapy

 age ≥ 18 years

Exclusion criteria: :

 unstable congestive heart failure

 active psychiatric disease

['No Sleep Apnea', 'Sleep Apnea - untreated', 'Sleep Apnea - treated']

No Sleep Apnea
Sleep Apnea - untreated
Sleep Apnea - treated

['Obstructive Sleep Apnea', 'End Stage Renal Disease']

Obstructive Sleep Apnea
End Stage Renal Disease


Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children

Summary: Evaluation of the following in very young children with Down syndrome:~the efficacy of systematic treatment with L-thyroxine at controlled doses (clinically and by ultrasensitive thyreostimulating hormone (TSH) assay),~the efficacy of systematic folinic acid treatment at a dose of 1 mg/kg/o.i.d,~any interaction between these two treatments.
Inclusion criteria: inclusion criteria:

 patient with a karyotype demonstrating homogeneous, free or Robertsonian translocation trisomy 21

 patient having undergone a cardiac ultrasound not demonstrating any severe heart disease

 patient aged 6 to 18 months at inclusion

Exclusion criteria: :

 congenital hypothyroidism

 hypothyroidism demonstrated by laboratory tests (TSH > 7mUI/l)

 presenting or having presented hyperthyroidism

 presenting or having presented leukaemia

 presenting or having presented West syndrome or any other form of epilepsy or unstable neurological disease

 presenting or having presented signs of central nervous system distress: stroke, postoperative hypoxia, meningitis)

 presenting severe heart disease on cardiac ultrasound, with haemodynamic effects

 presenting non-controlled cardiac arrhythmia

 Apgar < 7 to 5 min at birth

 Gestational age < 231 days (33 gestation weeks)


Thyroid Disorders in Malaysia: A Nationwide Multicentre Study

Summary: This will be a population based study looking at the prevalence of thyroid disorders in Malaysia (including hypo- and hyperthyroidism, subclinical hypo- or hyperthyroidism) and its association with different ethnicity and iodine status. The study will also look at genetic susceptibility for autoimmune thyroid disorders in the Malaysian population~General hypotheses:~The prevalence of thyroid disorders in Malaysia is 10% for hypothyroidism and 2% for hyperthyroidism Hypo- and hyperthyroidism is associated with iodine status in our population There are different susceptibility gene for autoimmune thyroid disorder in different ethnicity in our population
Inclusion criteria: inclusion criteria:

 Aged equal or more than 18 years old at the time of sampling

 Malaysian citizen

Exclusion criteria: :

 Respondents who did not give consent

['Hypothyroidism', 'Subclinical Hypothyroidism', 'Hyperthyroidism', 'Subclinical Hyperthyroidism', 'Graves Disease', "Hashimoto's Thyroiditis", 'Iodine Deficiency', 'Genetic Susceptibility']

Hypothyroidism
Subclinical Hypothyroidism
Hyperthyroidism
Subclinical Hyperthyroidism
Graves Disease
Hashimoto's Thyroiditis
Iodine Deficiency
Genetic Susceptibility

:

 Respondents who did not give consent


Analgesic Control Following Knee Arthroscopy

Summary: This study aims to investigate the analgesic effects offered by bupivacaine and Durolane (a hyaluronic acid supplement) administered immediately following the completion of knee arthroscopy.
Inclusion criteria: inclusion criteria:

 those undergoing knee arthroscopy for: diagnostic purposes, removal of loose bodies, articular cartilage debridement or, meniscectomy

 age over 18 years

Exclusion criteria: :

 American Society of Anaesthesiologists (ASA) grade ≥3;

 arthroscopic assisted osteotomies;

 a history of two or more prior procedures on the ipsilateral knee;

 post-operative morbidities indirectly linked to the procedure (e.g. anaesthetic complications, DVT or PE);

 systemic steroid requirements;

 previous intra-articular anaesthetic or steroid injection within the last three months;

 intra-articular HA injection within the last nine months;

 intra-articular sepsis within the previous three months;

 prior history of knee arthroplasty, peri-articular fracture, ligamentous instability, inflammatory arthritis or a previous diagnosis of Complex Regional Pain Syndrome.

['Intraarticular injection', 'Intra-articular injection of 0.5% Bupivacaine']


Involving Men in Maternity Care in Burkina Faso

Summary: The uptake of postpartum contraception, postpartum care attendance and the practice of exclusive breastfeeding are low in Sub-Saharan Africa. Although the involvement of men in maternity care has been shown to be a promising strategy for the achievement of other reproductive health goals, little is known about the effect of their participation on these outcomes. This study aims to test whether the involvement of men can improve care-seeking and promote healthy behaviours among postpartum women in Burkina Faso.
Inclusion criteria: inclusion criteria:

 Age 16-18, married, or

 Age 18+, in a co-habiting relationship

 Pregnant 24-36 weeks

 No obstetric risk factors requiring hospital delivery

 Lives no more than one hour away on foot, not planning to move from the city

 Gives informed consent

Exclusion criteria: :

 Not meeting inclusion criteria

 Declines to participate


The Diabetes Medication Adherence Promotion Intervention Trial

Summary: A significant percentage of persons with diabetes fail to properly take their prescribed oral hypoglycemic agents (OHA) and insulin. Non-adherence to medications among diabetes patients is associated with poor health outcomes including suboptimal glycemic control, diabetes-related complications, elevated health costs and increased risk of hospitalization and mortality. Given the substantial impact of non-compliance on the health of patients, prior studies have sought to draw links between medication adherence and patient factors.~Research shows that web-based interventions that support patients' medication-related knowledge, motivation and skills effectively improve compliance.~The purpose of this study is to evaluate the impact of a patient web portal (PWP)-delivered medication adherence promotion intervention on medication adherence and glycemic control among patients with type 2 diabetes (T2DM). The intervention aims to (1) increase self-reported adherence to glucose lowering agents (GLAs) and (2) improve diabetes health outcomes (decreased HbA1c) by increasing patients' medication adherence-related knowledge, motivation and skills.~This research will greatly enhance the investigators' understanding of medicine compliance and the factors that effectively improve adherence among high-risk patients with diabetes. Knowledge gained from this work may inform future internet-based patient portals that support disease management and medication adherence more broadly.
Inclusion criteria: inclusion criteria:

 Adults 18 years and older (to be confirmed by electronic health record)

 Individuals who have received a diagnosis for type 2 diabetes mellitus (T2DM)

 Enrolled as a patient in the Vanderbilt APPC or the Eskind Diabetes Clinic

 Registered My Health at Vanderbilt user

 Recent A1c of 7.0 or greater

 Individuals currently being treated with oral and/or injectable diabetes medication (to be confirmed through electronic health record)

Exclusion criteria: :

 Non-English speakers (determined by a trained research assistant)

 Individuals with a severe hearing or visual impairment (determined subjectively by a trained research assistant)

 Individuals with delirium or a severe cognitive impairment (determined by a lack of orientation to person, place, and time)

 Individuals who report a caregiver administers their diabetes medications

 Individuals who report they do not have a mobile phone or computer with internet access

 Individuals unwilling and/or unable to provide written informed consent


Expressive Writing for Heart Healing

Summary: This study will determine whether the psychological and physical benefits of expressive writing extend to obese in-patients with Ischemic Heart Disease (IHD)referred to cardiac rehabilitation
Inclusion criteria: inclusion criteria:

 obesity

 Ischemic Heart disease

 Signed informed consent

Exclusion criteria: :

 Visual or manual limitations that preclude reading and writing

 Unwilling to participate

['Disease-related Expressive writing', 'Active Comparator: Traditional expressive writing', 'Sham Comparator: Neutral writing']


Study to Evaluate the Effectiveness of Rotarix™ Against Severe Gastroenteritis Among Hospitalized Children in Brazil

Summary: The purpose of this study is to estimate the effectiveness of 2 doses of Rotarix™ vaccination in preventing rotavirus severe gastroenteritis among children hospitalized in Belem area, Brazil.
Inclusion criteria: inclusion criteria:

 For cases:

 A male or female child born after 6 March 2006 and at least 12 weeks of age.

 Subject admitted to the study clinics/hospitals for severe gastroenteritis during the study period.

 Onset of severe gastroenteritis ≤ 14 days prior to admission.

 Laboratory confirmed rotavirus positive stool sample at hospital admission or during the first 48 hours of hospitalization.

 Written informed consent obtained from the parent or guardian of the subject.

 For controls:

 Admitted for non-gastroenteritis causes at the same clinic/hospital as the case.

 Living in the same neighbourhood as the case for at least three consecutive months without any symptoms of gastroenteritis or severe gastroenteritis on the day of interview of his/ her parents/ guardians.

 Being born within +- 2 weeks from the date of birth of the case. If the number required is not available, then the range would be extended to +- 4 weeks, and ultimately up to +- 6 weeks for hospital controls. For neighbourhood controls, the range may be extended to +- 8 weeks.

 Written informed consent obtained from the parent or guardian of the child.

Exclusion criteria: :

 For cases:

 Subject has previously participated as case or control in this study.

 Onset of severe gastroenteritis > 48 hours after admission to the hospital (nosocomial infections).

 For controls:

 For hospital controls: Child who has symptoms of gastroenteritis during current hospitalization or on the day of interview of his/her parent or guardian or for neighbourhood controls: Child who has symptoms of gastroenteritis or severe gastroenteritis on the day of interview of his/her parent or guardian.

 Exclude children with the following vaccine preventable diseases: measles, mumps, rubella, diphtheria, pertussis, tetanus, tuberculosis, invasive Haemophilus influenzae type B (Hib) infections (meningitis, bacteraemia, septic arthritis, cellulitis, and epiglottitis) and hepatitis B.

 Child has participated in the past as a case or control in this study.

 Child living in the same house as the case


Children With Asthma in New Orleans After Hurricane Katrina

Summary: This study will examine whether exposure to the increased levels of mold and other allergens in New Orleans post-Hurricane Katrina affect symptoms in children with asthma. It will also determine if having an asthma counselor (AC) can reduce a child s asthma symptoms in this setting. An AC helps the families in the study obtain appropriate health care, medicines and social services for their asthmatic child and instructs them about avoiding allergens and ridding allergens from the home.~Children between 4 and 12 years of age living in Orleans Parish or surrounding areas impacted by flooding who have moderate to severe asthma may be eligible for this study.~Parents provide a family medical history and information about the child s asthma symptoms, medications and medical history. The children undergo the following procedures:~Medical examination and blood tests~Spirometry (for children 6 and older) or peak flow (for children under 6) test: For spirometry, the child wears a nose clip and breathes into a mouthpiece attached to a machine that measures how fast air moves out of the child s lungs. For the peak flow meter test, the child blows into a plastic tube after taking a deep breath.~Allergy skin testing: 24 common allergens are applied to the arm by little pricks or scratches and the skin is observed for reactions to the allergens.~Study staff visit the participants homes three times during the 1-year study to test for moisture, mold and other allergens. After the first visit, families are randomly assigned to one of two groups. Group 1 participants attend two educational group sessions about asthma and then three individual sessions. An AC visits the home one time during the study to instruct the family on how to use supplies provided to reduce allergens in the home. Group 2 participants have an individual special teaching meeting with the AC at the end of the study. After the meeting, the AC visits the home to instruct the family on use of the supplies.~Families are surveyed by phone every 3 months during the study to answer questions about the child s asthma attacks, medicines used, doctor visits, school days, missed, or work days missed to care for the child. At the end of the study, the child has a final medical examination, blood test, and breathing test.
Inclusion criteria: inclusion criteria:

 A child will be included in the HEAL intervention study if he or she:

 Is a male or female child four to twelve years old, inclusive, at the time of recruitment, living in Orleans Parish or surrounding areas impacted by flooding.

 Has previously been given a diagnosis of asthma by a healthcare provider and who has symptoms as described below (Criteria 3) for more than one year.

 Is currently receiving long-term asthma control therapy, as reported at baseline, and either has symptoms consistent with persistent asthma (criterion 3a, see below) or has evidence of uncontrolled disease (criterion 3b); or is not currently receiving long-term asthma control therapy and has symptoms consistent with persistent asthma (criterion 3a) and also has evidence of uncontrolled disease (criterion 3b):

 3a. Evidence of persistent asthma as defined by the National Asthma Education and Prevention Program (NAEPP) of the National Heart Lung and Blood Institute Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma (1997), which includes: asthma symptoms 3 or more days per week during the last two weeks, sleep disturbed due to asthma at least 3 times in the past month, or albuterol use (Metered Dose Inhaler or nebulizer) for quick relief at least 8 times in the past two weeks, not including use as a preventive for exercise.

 3b. Evidence of uncontrolled disease as defined by at least one of the following additional criteria:

 i. One asthma-related unscheduled visit to an emergency department (ED), urgent care (UC), or clinic in the previous 12 months.

 ii. One asthma-related overnight hospitalization in the previous 12 months.

 iii. One or more bursts of oral corticosteroids or equivalent in the previous 12 months.

 4) Has a parent or legal guardian willing to sign the written informed consent prior to initiation into the study.

 5) Is willing to sign the assent form, if age appropriate.

Exclusion criteria: :

 A child will be excluded from the HEAL intervention study if she or he:

 Is defined as having mild intermittent asthma at baseline evaluation.

 Has had a life-threatening asthma exacerbation in the last 5 years requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure.

 Has significant medical illnesses other than asthma such as: any hematologic, endocrine, respiratory (other than asthma) or cardiac condition requiring daily medications; significant neurological disorder requiring daily medications; any clotting disorder; any obvious severe mental retardation that prohibits the child or the child s caregiver from answering questions or following instructions; any autoimmune disease; any immune deficiency; or any other serious medical condition including Juvenile diabetes mellitus, hypo- or hyper- thyroidism, hemophilia, Von Willebrands disease, sickle cell disease, cerebral palsy, rheumatoid arthritis, lupus, psoriasis, hyperimmunoglobulin E syndrome, or diagnosed allergic bronchopulmonary aspergillosis.

 Has not had a home evaluation completed within 4-6 weeks of the Screening Visit (may be re-screened).

 Lives with a foster parent.

 Has caregiver (typically the parent or guardian) who does not have access to a phone.

 Plans to move out of the recruitment area over the next year.

 One child from each household will be selected to participate in the study. In the case of multiple eligible children, the youngest child will be included in the study.


Early Behavioral Intervention for Preterm Infants

Summary: The purpose of this study is to determine the effects of Family Nurture Intervention in preschool aged children between 2.5 and 4.5 years of age who were born prematurely and exhibit developmental deficits. The new approach is based on improving aspects of maternal nurturing behaviors as well as mother-child co-regulation, which are important to early development. Since young children with developmental deficits are often easily upset, mothers will be taught how to co-regulate with their child through comfort and calming interactions during 11 clinic visits. Assessments in the follow-up clinic will test the immediate and long-term effects of this new approach to the nurture of children who were born early and demonstrate developmental problems and behavioral problems.
Inclusion criteria: inclusion criteria:

 Infant is a singleton (matched between groups)

 Mother is 18 years of age or older

 Mother has at least one supporting person in the home (e.g. significant other, mother, father, sibling, aunt, grandmother, step-parent)

 Child demonstrates developmental deficit (language, cognition, motor, emotion)

Exclusion criteria: :

 The child has severe congenital anomalies including chromosomal anomalies

 The child has severe motor or physical disability

 Mother currently presents with psychosis or is currently taking antipsychotic medication

 Status of enrolled subject changes and subject no longer falls in inclusion criteria

 Mother and/or infant has a medical condition that precludes intervention components

 Mother and/or infant has a contagion that endangers other participants in the study

['Family Nurture Intervention', 'Play and Nutrition Intervention']

Family Nurture Intervention
Play and Nutrition Intervention


Triple in Asthma Dose Finding

Summary: The purpose of this study is to determine the optimal dose of CHF 5259 (glycopyrrolate bromide) on top of Foster which provides the optimal additive bronchodilator effect to asthmatic patients whose symptoms are uncontrolled with medium dose of inhaled corticosteroids plus long acting beta2 agonists.
Inclusion criteria: inclusion criteria:

 Male or female patients aged >=18 years

 Uncontrolled asthma on medium doses of ICS+LABA with ACQ >=1.5

 Pre-bronchodilator FEV1 ≥40% and <80% of their predicted normal value

Exclusion criteria: :

 Pregnant or lactating women

 Diagnosis of COPD

 Patients treated for asthma exacerbations in the 4 weeks prior to study entry

 Patients who are in therapy for gastroesophageal reflux disease

 Patients who have a clinically significant cardiovascular condition

['CHF 5259 plus Foster 100/6 µg', 'Foster 100/6 µg']

CHF 5259 plus Foster 100/6 µg
Foster 100/6 µg


Study of Risperidone Monotherapy in Ambulatory Bipolar Disorder With Concurrent Moderately Severe Anxiety and Lifetime Panic or Generalized Anxiety Disorder

Summary: The purpose of this research study is to evaluate the safety, tolerability, and efficacy (how well the drug works) of risperidone compared to placebo (an inactive drug) in the treatment of bipolar disorder with panic disorder or generalized anxiety disorder. Risperidone is currently approved by the United States Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar mania. Risperidone is not currently FDA approved for the treatment of bipolar hypomania with or without panic disorder or generalized anxiety disorder (the condition being investigated in this study).
Inclusion criteria: inclusion criteria:

 Subjects must be 18 years of age or older.

 Subjects must have lifetime bipolar I, II, or NOS disorder as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.

 Subjects must have lifetime panic disorder or generalized anxiety disorder (GAD) as defined by DSM-IV criteria (except clause does not occur exclusively during a mood disorder of Criterion F for GAD) .

 Subjects' bipolar symptoms must be no more than moderately severe, defined as a CGI-BP < 4.

 Subjects' anxiety symptoms must be at least moderately severe, defined as a CGI-S > 4.

 Subjects must not be receiving mood stabilizing, antidepressant, antipsychotic, or anxiolytic medication for > one week prior to baseline. Patients receiving fluoxetine or depot antipsychotics should be off these medications for > four weeks prior to baseline.

 Subjects or their legally authorized representative must sign the Informed Consent Document after the nature of the trial has been fully explained.

 If female, subjects must be:

 postmenopausal,

 surgically incapable of childbearing,

 or practicing medically acceptable effective method(s) of contraception (e.g., hormonal methods, barrier methods, intrauterine device) for at least one month prior to study entry and throughout the study.

Exclusion criteria: :

 Subjects who do not have lifetime bipolar disorder by DSM-IV-TR (text revision) criteria.

 Subjects who do not have lifetime panic disorder or generalized anxiety disorder by DSM-IV-TR criteria.

 Subjects who are receiving treatment with an antimanic or mood stabilizing medication (lithium, valproate, carbamazepine, or an antipsychotic), and in the investigators' judgment, require ongoing treatment with that medication.

 Subjects whose bipolar symptoms are presently more than moderately severe (CGI-BP > 5).

 Subjects whose anxiety symptoms are presently less than moderately severe (CGI < 3).

 Subjects with clinically significant suicidal or homicidal ideation.

 Subjects with current psychotic symptoms.

 Subjects with a current DSM-IV Axis I diagnosis of delirium, dementia, amnesia, or other cognitive disorders; a DSM-IV diagnosis of a substance dependence disorder within the past six months; or a lifetime DSM-IV psychotic disorder (e.g., schizophrenia or schizoaffective disorder).

 Subjects with serious general medical illnesses including hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, or hematologic disease as determined by the clinical judgment of the clinical investigator. Subjects with hypo- or hyperthyroidism unless stabilized on thyroid replacement > 3 months.

 Subjects with a clinically significant abnormality in their prestudy physical exam, vital signs, EKG, or laboratory tests.

 Subjects who are allergic to or who have demonstrated hypersensitivity to risperidone.

 Women who are pregnant or nursing.

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

 Subjects who have a history of neuroleptic malignant syndrome.

['Bipolar Disorder', 'Anxiety Disorder']


Biologic Predictors of Leiomyoma Treatment Outcomes

Summary: The purpose of this study is to search for the hereditary (genetic) causes of uterine fibroids. Some women with uterine fibroids may have one or more genes that make them more likely to develop uterine fibroids. We are trying to identify these genes to better understand how and why uterine fibroids develop and to design better treatment options for women with uterine fibroids. This information may also help us to understand and treat other problems that may be caused by these genes.
Inclusion criteria: inclusion criteria:

 Able and willing to give consent

 Age 18 or older

 Presence of known uterine leiomyoma

Exclusion criteria: :

 1. Suspected malignancy

['Uterine Leiomyomas', 'Fibroids', 'Uterine Fibroids', 'Myomas']

Uterine Leiomyomas
Fibroids
Uterine Fibroids
Myomas


Dexmedetomidine and Delirium in Patients After Cardiac Surgery

Summary: Postoperative delirium (POD) is a frequently occurring complication after cardiac surgery. Its occurrence is associated with worse outcomes of patients, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. It is also associated with long-term cognitive decline and decreased quality of life. However, until recently, pharmacological interventions that can effectively prevent its occurrence are still limited. The purpose of this study is to investigate whether perioperative dexmedetomidine use can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery.
Inclusion criteria: inclusion criteria:

 Patients of 60 years or older who are planning to receive cardiac surgery (CABG and/or valve replacement surgery)

Exclusion criteria: :

 Patients will be excluded if they meet any of the following criteria:

 Refuse to participate;

 Preoperative history of schizophrenia, epilepsia, Parkinson syndrome, or severe dementia;

 Inability to communicate in the preoperative period because of severe visual/auditory dysfunction or language barrier;

 History of brain injury or neurosurgery;

 Preoperative sick sinus syndrome, severe bradycardia (HR < 50 bpm), second-degree or above atrioventricular block without pacemaker;

 Severe hepatic dysfunction (Child-Pugh class C);

 Severe renal dysfunction (requirement of renal replacement therapy);

 Other conditions that are considered unsuitable for participation.

['dexmedetomidine hydrochloride for injection', '0.9% sodium chloride for injection']

['Delirium', 'C.Surgical Procedure; Cardiac', 'Postoperative Complications']

Delirium
C.Surgical Procedure; Cardiac
Postoperative Complications


PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT Pilot)

Summary: PROTECT Pilot objective is to assess: 1) the feasibility of timely enrollment and complete, blinded study drug administration, 2) the bioaccumulation of LMWH in patients with acquired renal insufficiency and its association with bleeding, 3) the feasibility of scheduled twice weekly lower limb ultrasounds, and 4) recruitment rates for a future randomized trial.
Inclusion criteria: inclusion criteria:

 Admission to ICU

 Men and women greater than 18 years of age or older

 Expected to remain in ICU admission greater than 72 hours

Exclusion criteria: :

 Contraindications to LMWH or blood products

 Trauma, post orthopedic surgery, post cardiac surgery or post neurosurgery patients,

 Uncontrolled hypertension as defined by a systolic blood pressure > 180 mmHg or a diastolic blood pressure > 110 mmHg,

 Hemorrhagic stroke, DVT, PE or major hemorrhage on admission or within 3 months,

 Coagulopathy as defined by INR >2 times upper limit of normal [ULN], or PTT >2 times ULN,

 Renal insufficiency as defined by a creatinine clearance <30ml/min,

 A need for oral or intravenous or subcutaneous therapeutic anticoagulation,

 Heparin allergy, proven or suspected heparin-induced thrombocytopenia (HIT),

 Receipt of >2 doses of UFH or LMWH in ICU,

 Pregnant or lactating,

 Withdrawal of life support or limitation of life support,

 Prior enrollment in this trial

 Prior enrollment into a related RCT

 Thrombocytopenia defined platelet count < 100 x 109/L,

 Bilateral lower limb amputation,

 Allergy to pork or pork products

['Fragmin (Dalteparin) LMWH verus Unfractionated Heparin (UFH)']

['Critically Ill', 'Deep Venous Thrombosis']


Influence of Transmission Season on Outcome of Treatment of Schistosoma Haematobium Infection in Mozambique

Summary: To assess the influence of seasonal variations in Schistosoma haematobium transmission on treatment outcome (morbidity and re-infection)
Inclusion criteria: inclusion criteria:

 children aged 8-12 years

Exclusion criteria: :

 All children presenting with macro-haematuria or severe pathology detected by ultrasonography (large masses, pseudo-polyps or hydronephrosis/hydroureter) at the 6 months follow-up examination will be treated with praziquantel and excluded in the data analysis.


Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil

Summary: Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysethesia (PPE), occurs in a 25%-50% of patients treated with several commonly used anti-cancer drugs including capecitabine and sunitinib. These drugs are known to improve survival in many cancers, including cancers of the colon, stomach, liver, breast, kidney, and GI stromal tumors (GIST). Worldwide, over 400,000 patients per year are treated with one of these agents. HFS involves skin changes, such as swelling, peeling, and blistering of the palms and soles, which is often painful and debilitating. As a result, HFS-related symptoms can frequently lead to dose reduction and/or discontinuation of otherwise effective anti-cancer treatment. There is no treatment for HFS other than dose reduction or stopping treatment. This proposal could quickly lead to treatments to prevent and/or treat HFS and help patients avoid debilitating side effects while continuing otherwise effective treatments for their cancer.
Inclusion criteria: inclusion criteria:

 Subjects must meet the following criteria to be eligible for the study:

 Receiving capecitabine or sunitinib as part of routine standard care.

 CTCAE version 4.0, grade 1-3 PPE.

 Adults age ≥ 18

 Karnofsky (KPS) performance status of ≥70%

 Adequate organ and marrow function as defined below:

 - ANC > 1000/mL

 - Platelets > 75,000/mL

 - Total bilirubin < 1.5 x UNL

 - AST(SGOT)/ALT(SGPT) < 5 x UNL

 - Creatinine Cr Cl est > 40 mL/min (by Cockcroft-Gault)

 Not pregnant or lactating.

 Use of adequate birth control with female partners of male subjects agreeing to use a medically acceptable form of birth control: (1) surgical sterilization, (2) approved hormonal contraceptives (such as birth control pills or Depo-Provera), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, (4) an intrauterine device (IUD) or (5) post menopausal. Abstinence is not considered acceptable birth control. Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.

 Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria: :

 Subjects meeting any of the following criteria are ineligible for study entry:

 Currently participating in a clinical trial.

 History of hypersensitivity or intolerance to sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™) or poloxamer vehicle.

 Currently taking oral sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™).

 Currently taking other treatment for PPE other than standard emollients.

 Using organic nitrates, either regularly and/or intermittently, in any form.

 History of myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.

 Resting hypotension (BP <90/50 mmHg) or hypertension (BP >170/110 mmHg). Those subjects on alpha-blocker or anti-hypertensive therapy must be hemodynamically stable for at least two weeks before day 1 of study drug.

 Cardiac failure or coronary artery disease causing unstable angina.

 Known retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

 Concomitant use of strong cytochrome P450 3A4 inducers or inhibitors (Ex: ketoconazole, itraconazole, erythromycin, saquinavir).

 Other acute or chronic inflammatory conditions or infections of the hands or feet that would complicate safety, application of topical creams, or study endpoints.

 History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.

 Pregnant or breast-feeding and/or lactating.

 Inability or unwillingness to comply with protocol.

['Hand Foot Syndrome', 'Palmar Plantar Erythrodysesthesia']

Hand Foot Syndrome
Palmar Plantar Erythrodysesthesia


The Assessment of Right Ventricular Contractility in Response to Sildenafil

Summary: The primary objective of this study is to examine the effects of Sildenafil, administered during cardiac catheterization, on right ventricular contractility in children with pulmonary arterial hypertension.
Inclusion criteria: inclusion criteria:

 Significant pulmonary arterial hypertension (mean pulmonary artery pressure > 25 mm Hg)

 Patients aged 4-18 years

 Routine cardiac catheterization clinically indicated for deciding therapeutic treatment

 Informed assent/consent from patient/parent

Exclusion criteria: :

 Suprasystemic pulmonary artery pressures

 Evidence of right heart failure

 History of ventricular arrhythmia

 Known vascular access arrhythmia

 Contraindication to Sildenafil

 Concurrent inotropic / PDE administration

 Other medical, psychological or social circumstances which complicate a regular participation in the study, and/or increase the risk for the patients themselves

 No consent/assent

 Pregnancy or unwillingness to comply with contraceptive advice


An Adipocyte-Driven Mechanism For Weight Regain After Weight Loss: The Yo-Yo Effect

Summary: Almost half of the Dutch population is currently characterized by overweight and obesity. Losing weight is not the problem in obesity treatment, it is the seemingly obligatory weight regain after weight loss: the yoyo-effect. The primary objective of this study is to investigate the association between the weight-loss-induced cellular stress response and the rate of weight regain. The secondary objective is to investigate the differences in cellular stress response and weight regain after rapid and slow weight loss. To investigate this, subjects will receive meal replacements replacing either all or part of the daily meals during the intervention period. THe first group will consume 500 kcal/d diet for 5 weeks while the second group consumes a 1250 kcal/d diet for 3 months, both followed by 1 week normalization and a 2 week strict weight maintenance diet. During the 9-month follow-up period subjects will receive dietary advice according to the Dutch recommendations for healthy eating. The association between the amount of weight regain after the weight loss period and changes in adipokines, parameters of adipocyte metabolism, in vivo adipose tissue metabolism, adipocyte extracellular matrix gene expression profiles, adipocyte stress protein expression and gene polymorphisms in selected genes.
Inclusion criteria: inclusion criteria:

 Age (years): 20-65

 Body Mass Index (kg/m2): 28-35

 Non-smokers

Exclusion criteria: :

 Subjects using prescription medication, or suffering from diseases or conditions that might influence the outcome of the study: this concerns diseases/medication that influence body weight regulation (malabsorption, untreated hypo/hyperthyroidism, eating disorders, systemic use of steroids, etc.) and obesity-related cardiovascular risk factors (heart disease, systolic and diastolic blood pressures > 160/100 mmHg, blood glucose > 6.1 mmol L-1, blood cholesterol > 7 mmol L-1, blood triglycerides > 3 mmol L-1)

 marked alcohol consumption > 21 alcoholic units week-1 (male), or >14 alcoholic units week-1 (female)

 planned major changes in physical activity during the study to an extent that might interfere with the study outcome as judged by the investigator;

 blood donation within the past 2 months prior to the study

 weight change of >3 kg within 2 months prior to the study

 psychiatric disease (based on medical history only)

 pregnant or lactating women, or women planning to become pregnant within the next 12 months

 surgically treated obesity

 participation in other clinical studies within the last 3 months

 drug abuse (based on clinical judgment)

 unable to give informed consent

 unable to engage in a low-calorie diet

 unable to lose more then 8% of body weight after weight-loss period

 following a special diet (vegetarian, Atkins or other).

['Meal replacement diet using Modifast', 'Normal diet combined with Modifast diet']

Meal replacement diet using Modifast
Normal diet combined with Modifast diet


Delirium in the Emergency Department: Novel Screening

Summary: Delirium is an acute confusional state characterized by altered or fluctuating mental status, inattention, and either disorganized thinking or an altered level of consciousness. This form of organ dysfunction occurs in up to 10% of older emergency department (ED) patients and is associated with worsening mortality, prolonged hospital length of stay, higher health care costs, and accelerated functional and cognitive decline. Despite the negative consequences of delirium, the majority of cases are unrecognized by emergency physicians because it is not routinely screened for. In an effort to facilitate delirium screening, the investigators sought to validate three brief delirium assessments in the ED setting.
Inclusion criteria: inclusion criteria:

 65 years of age or greater

 In the Emergency Department for less than 12 hour at the time of enrollment

Exclusion criteria: :

 Severe mental retardation or dementia

 Baseline communication barriers such as aphasia, deafness, blindness, or who are unable to speak English

 Refusal of consent

 Previous enrollment

 Comatose

 Out of the hospital before the assessments are completed


Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas

Summary: Colon cancer is the second most common cancer in men and women. It is a disease that can be prevented if it is found early. Colonoscopy is still the best screening tool for colon cancer and the polyps that turn into colon cancer. However, due to a variety of factors, including affordability, time, and age, not all patients are able to be screened. Researchers are working on other options for early detection that are as accurate as colonoscopy.~The purpose of this study if to determine if stool or blood can be used to detect colon cancers as early or earlier than colonoscopy. The researchers plan to use these samples to learn about specific proteins (also known as biomarkers) that may indicate colon polyps, colon cancer or an increased risk of developing colon cancer. In order to learn more about preventing and detecting colon and rectal cancer, we are collecting samples from subjects with cancer, adenomas, and colonoscopies who may be at risk for polyps.
Inclusion criteria: inclusion criteria:

 Willing to sign informed consent

 Able to physically tolerate removal of up to 60 ml of blood

 Adults at least 18 years old

 Willing to collect 1-2 stool samples and prepare a Fecal Immunochemical Test (FIT)

 Pregnant or nursing women who otherwise meet the eligibility criteria may participate

 Subjects with one of the following:

 Colorectal adenocarcinoma-not treated and in colon at time of stool collection (CRC bin)

 Adenoma-pathologically confirmed adenoma present in colon at time of stool collection (Adenoma Bin)

 Higher Risk Non-neoplastic Bin

 Subjects with a personal history of adenomas (confirmed by pathology) with none present on qualifying colonoscopy

 Subjects with a personal history of CRC (longer than 3 years ago because of
Exclusion criteria:  of cancer within last 3 years) with none present at time of qualifying colonoscopy

 Any family history of CRC (1st degree relative)

 Current positive screening stool test for blood, for DNA or for both within 12 months with no follow-up intervention.

 Average Risk, Non-neoplastic Bin

 No history or current finding of any colorectal neoplasia including CRC, adenomas, sessile serrated adenomas and no family history of CRC.

 Subjects who had CRC that was successfully treated at least three years ago may be considered eligible for the adenoma bin if their polyps are adenomas and there is no evidence of CRC, or for the higher risk non-neoplastic bin as noted above.

 Subjects whose screening colonoscopy shows any of these types of polyps may be included in the non-neoplastic or the higher risk non-neoplastic bin if they meet the other criteria noted above.

 Hyperplastic polyps

 Benign mucosal polyps

 Polypoid granulation tissue

 Prolapsed mucosal polyps

 Inflammatory polyp

 Transitional mucosal polyp

 Lipoma

 Gangleoneuroma

 Neuroma

 Hamartomatous polyp


Potential Use Of Brain Network Activation Analysis to Diagnose Major Depression

Summary: The investigators are doing this study to find out if they can use electroencephalographic (EEG) recordings, which measure brain waves, to predict response to antidepressant treatments, as well as to distinguish patients who have depression from those who do not. In particular the investigators want to test the usefulness of a new type of analysis of EEG recordings called brain network activation or BNA. BNA allows to identify patterns of activation in brain networks and to track their changes over time.
Inclusion criteria: For Patients with Major Depressive Disorder

 inclusion criteria:

 • Male and female outpatients, aged 18-55 years

 Subjects meeting full criteria for the diagnosis of current Major Depressive Disorder (MDD) without psychotic features, as determined by clinical evaluation and Mood Module of structured diagnostic interview (SCID), completed by the study clinician.

 HAM-D17 score of 14 or higher

 Able to provide informed consent

 Right handed, normal (corrected) vision and normal hearing

Exclusion criteria: :

 • Other primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia, attention deficit hyperactivity disorder (ADHD).

 Substance use disorder (abuse or dependence with active use within the last 6 months).

 Significant sensory deficits such as deafness or blindness.

 Severe or unstable medical illness, including history of closed head injury resulting in loss of consciousness, seizure disorder; history of neurological disorders.

 Pregnant or nursing females who are not using an accepted method of contraception (birth control pill, IUD, combination of barrier methods)

 Clinically significant abnormal laboratory values or electrocardiogram For Healthy Controls

 inclusion criteria:

 Males and females, aged 18-55 years

 Subjects who do not meet full criteria for any of the major psychiatric diagnosis including MDD, bipolar disorder, schizophrenia, substance abuse/dependence, attention deficit hyperactivity disorder (ADHD), as determined by clinical evaluation and structured diagnostic interview, completed by the study clinician.

 Right handed, normal (corrected) vision and normal hearing


Polish Survey on the Efficacy of the Hypercholesterolemia Treatment

Summary: The purpose of the survey is to evaluate the efficacy of treatment of hypercholesterolemia in Polish patients who are currently on lipid- lowering pharmacological therapy . Efficient treatment is defined as achievement of the LDL cholesterol level goals according to the European Society of Cardiology 2007 guidlines.
Inclusion criteria: inclusion criteria:

 Patients on lipid lowering drug treatment

 Lipid lowering drug treatment lasting at least 3 months

 No lipid lowering drug/dose change for a minimum 6 weeks prior to enrolment to the study

Exclusion criteria: :

 Lack of patient's signed informed consent form

 Lack of the blood sample taken for lipid profile and glucose within 10 days before or after assessment of the patient


Sleep Apnea Screening

Summary: To assess the incidence of Sleep Apnea-Hypopnea Syndrome (SAHS), both obstructive and central, in patients with: 1) pacemaker indication; 2) implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRTD), 3) heart failure and preserved left ventricular ejection fraction (LVEF) and 4) heart failure and reduced LVEF.
Inclusion criteria: inclusion criteria:

 Age 18 years or older

 No previous diagnosis of sleep apnea

 Fulfilling at least one of the following:

 Pacemaker indication

 ICD or CRTD therapy indication

 Heart failure and preserved LVEF (40-50%)

 Heart failure and reduced LVEF (<40%)

 Signed informed consent

Exclusion criteria: :

 Age younger than 18 years

 Renal hemodialysis

 Cardiac transplant indication

 Women who are pregnant

 Advanced cancer

 Enrollment in another investigational study

 Able and willing to comply with all testing and requirements

 Patient not suitable for inclusion due to psychiatric conditions or short life expectancy

['Berlin and Epworth questionaries', 'Sleep apnea monitoring in those patients in whom a pacemaker with monitoring apnea system has been implanted.', 'Night polygraph / Polysomnography']


Factors Predicting Response to Shunting in Normal Pressure Hydrocephalus

Summary: The research project is designed to determine which combination of tests will enable physicians to predict whether a patient with symptoms of normal pressure hydrocephalus (NPH) will improve with a shunt.
Inclusion criteria: inclusion criteria:

 Walking difficulties in both legs which has developed gradually, not explained by other conditions, either in combination with mental impairment and urinary incontinence

 Brain CT or MRI findings of enlarged ventricles compared to established standards (minimum Evans ratio of 0.30 as measured by reviewing films)

 Mental impairment must be mild to moderate, emerging with or after the walking difficulties

 Age > or = 18 years old

 MMSE (Mini-mental status exam): < or = 10

 Urinary incontinence

Exclusion criteria: :

 No or only minimal walking difficulties combined with severe dementia

 Severe medical problems with limited life expectancy (less than six months)

 Contraindications to surgery

 Lack of informed consent

['Programmable Shunt Insertion (Codman, Medtronic)', 'Assessments in physical therapy, occupational therapy, and speech therapy']

Programmable Shunt Insertion (Codman
Medtronic)
Assessments in physical therapy
occupational therapy
and speech therapy


The Effect of Hyperbaric Chamber Treatment on Patients With Diabetic Retinopathy

Summary: Diabetic retinopathy (DR) is a common complication of diabetes and is divided into non proliferative DR and proliferative DR. The damage is caused by either macular edema, macular ischemia that can be followed by vascular proliferation.~Hyperbaric chamber treatment assists in increasing the amount of oxygen in the plasma and in the tissues and has been proven to be beneficial in treating different wounds in diabetic patients but its effect hasn't been tested in diabetic retinopathy yet.~This study will recruit 40 diabetic patients who are scheduled for hyperbaric treatment due to different indications such as chronic wounds or radiation damages and who also have diabetic retinopathy. These patients will undergo opthalmic physical examination including fundus photography and OCT (Optical Coherence Tomography - optical IR retinal photography). Screening for these patients will be conducted at the Hyperbaric chamber at Assaf Harofe Medical Center for all diabetic patients prior to their first treatment.
Inclusion criteria: inclusion criteria:

 inclusion criteria:

 Patients between ages 18-90 with Diabetes type I or II and diabetic retinopathy who are scheduled for hyperbaric treatment for other indications than DR.

 Patients who signed an informed consent form and agree to undergo an ophthalmic physical examination, Fundus photography and OCT prior to hyperbaric treatment and oCT exam following every 10 treatments in hyperbaric chamber. Total number of hyperbaric treatments will be conducted according to the main indication for which they have been assigned this treatment.

Exclusion criteria: :

 Patients with Carotid stenosis of more than 70%

 Anemia of < 10mg/Dl

 Patients with chest X ray pathology which cannot be admitted to hyperbaric chamber treatment.

 Patients with claustrophobia or that cannot decompress properly.

 Patients with any malignant disease

 Patients with inability to sign informed consent

 Decompression treatment will last 90 minutes in 2 atmospheres pressure with 100% oxygen.

 -

['Does Hyperbaric Chaber Treatment Improve Diabetic Retinopathy']


A Study to Evaluate Safety and Tolerability in Patients With Metastatic Breast Cancer Receiving Treatment With Caelyx (Study P04878)(COMPLETED)

Summary: This is a study to evaluate the safety and tolerability of Caelyx used for the treatment of metastatic breast cancer (MBC), focusing on infusion reaction and palmar-plantar erythrodysesthesia (PPE).
Inclusion criteria: inclusion criteria:

 Patients with metastatic breast cancer

Exclusion criteria: :

 History of hypersensitivity to Caelyx or its components

 Women who are pregnant or breast-feeding

 Patients with severe myelosuppression


A Phase II Non-Controlled, Open-Label, Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Study of Pacritinib in Myelofibrosis

Summary: To evaluate the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of pacritinib in Asian subjects with myelofibrosis (MF), which includes primary MF (PMF), post-polycythemia vera MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF).
Inclusion criteria: inclusion criteria:

 Intermediate-1, intermediate-2, or high-risk PMF, PPV-MF or PET-MF as based on The Dynamic International Prognostic Scoring System (DIPSS) criteria

 Palpable splenomegaly ≥5 cm below the LCM in midclavicular line by physical examination

 TSS ≥13 on the MPN-SAF TSS 2.0, not including the inactivity question, based on a single assessment during screening visit

 Age ≥18 years old at the time of screening (or minimum age of legal consent consistent with local regulations, if minimum is >18 years of age)

 ECOG performance status 0 to 3

 Peripheral blast count <10%

 Absolute neutrophil count >500/μL

 Participants who are platelet or RBC transfusion dependent are eligible

 Adequate liver and renal function, defined by liver transaminases (AST/serum glutamic oxaloacetic transaminase [SOOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]) ≤3 × upper limit of normal ([ULN], AST/ALT ≤5 × ULN if transaminase elevation is related to MF), direct bilirubin ≤4 × ULN, and creatinine ≤2.5 mg/dL

 At least 6 months from prior splenic irradiation

 At least 12 months from prior 32P therapy

 At least 1 week since prior treatment (most recent dose) with a potent CYP3A4 inhibitor or inducer

 At least 4 weeks since any experimental treatment for PMF, PPV-MF, or PET-MF

 At least 2 weeks since any treatment for PMF, PPV-MF, or PET-MF

 If fertile, both males and females must agree to use effective birth control.

 Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument and comply with treatment and study procedures of the protocol

 Able to understand and willing to sign the informed consent form (ICF)

 Participant is willing and able to comply with the requirements of the protocol

Exclusion criteria: :

 Any GI or metabolic condition that could interfere with absorption of oral medication

 Life expectancy <6 months

 Prior treatment with a JAK2 inhibitor

 Completed ASCT, or are eligible for and willing to complete ASCT

 History of splenectomy or planning to undergo splenectomy

 Uncontrolled intercurrent illness, including but not limited to ongoing active infection, or psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements

 Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ confined, or treated non-metastatic prostate cancer with negative prostate specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma

 Inflammatory or chronic functional bowel disorder, such as Crohn's disease, inflammatory bowel disease, chronic diarrhea, or constipation

 Clinically symptomatic and uncontrolled cardiovascular disease

 History of any of the following within 6 months prior to first dose of pacritinib: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure

 New York Heart Association Class II, III, or IV congestive heart failure

 Participants with NCI CTCAE (version 4.03) Grade 2 cardiac arrhythmias may be considered for inclusion, with the approval of the medical monitor, if the arrhythmias are stable, asymptomatic and unlikely to affect participant safety. Participants will be excluded if they have ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥3, QTc prolongation >450 ms, or other conditions that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)

 Erythropoietic agent within 28 days prior to first dose of pacritinib

 Thrombopoietic agent within 14 days prior to first dose of pacritinib

 Known seropositivity for human immunodeficiency virus or syphilis, or known active hepatitis A, B or C virus infection

 Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study

 Participant is a family member or employee of the investigator

 If female, participant is pregnant or breastfeeding at the time of enrollment. Even if breastfeeding can be discontinued, the participant should not be enrolled in the study


Study of the Efficiency of Esophageal Dilation on Patient With Eosinophilic Esophagitis

Summary: This study is for patients who have had a food impaction and/or difficulty swallowing, who are scheduled to have endoscopy, biopsy and possibly dilatation (stretching) of the esophagus.~Standard treatment for people who have food impaction and difficulty swallowing is endoscopy to view the esophagus, tissue biopsies of the lining of the esophagus for diagnosis, and drug therapy including steroids and drugs used to treat reflux disease. Early dilatation or stretching of the esophagus may be done at this time but not always. Some doctors prefer to wait and see if the drugs are affective.~It is not known if dilating the esophagus early in treatment adds benefit. Therefore, we are doing this study to compare the two methods of treatment. We will compare two groups: one group will have dilatation performed during the first endoscopy and one group will not have dilatation performed during endoscopy. We will see if dilatation helps prevent food impaction and improves swallowing.~Another purpose of this study is to learn more about the causes of swallowing problems, thus extra biopsies will be taken of the esophagus and store them for future research.
Inclusion criteria: inclusion criteria:

 Male and female volunteers ≥18 years old.

 Patients with known or suspected Eosinophilic Esophagitis.

 Patients undergoing upper endoscopy for recent food impaction or complaint of dysphagia.

Exclusion criteria: :

 Use of oral corticosteroids.

 Significant medical conditions that in the investigator's judgment would compromise the subject's health and safety.

 Contraindication to esophageal dilation based on investigator's judgment.

 Esophageal motility abnormalities not thought to be related to Eosinophilic Esophagitis.

['Esophageal dilation', 'Steroid and Proton Pump Inhibitor Therapy']


Prophylactic Effect of Lamotrigine Compared With Lithium in Bipolar Disorder

Summary: The purpose of this study is to compare lamotrigine with lithium in the long term treatment of bipolar disorder in terms of new episode preventive potentials.
Inclusion criteria: inclusion criteria:

 Age above 18

 Inclusion is preceded by an affective episode requiring hospitalisation or outpatient drug treatment (index episode) which can be a manic episode (ICD-10 research criteria), a depressive episode of at least moderate degree (ICD-10 research criteria) or a mixed manic state (manic episode with at least additional three ICD-10 depressive symptoms except for difficulties with concentration or thinking, agitation or dyssomnia). The episode can be with or without psychotic symptoms including Schneiderian first-rank symptoms or bizarre delusions as long as the psychotic symptoms do not occur outside the affective episode.

 No more than 12 months may pass between the onset of the index episode (or admission if that is the case)and date of randomisation (in order to ensure a current risk of relapse as well as reliable psychopathological information).

 Besides the index episode, at least one previous episode must have occurred within the last five years which meets the criteria mentioned in point number two above. This episode may not necessarily have led to hospitalisation. Two episodes are separated by at least two months without significant symptoms or change in polarity (depression to mania/mixed mania or vice versa).

 At least one manic episode (or mixed manic episode) within the last 5 years.

Exclusion criteria: :

 Contraindications to the protocol drugs.

 Severe somatic disease, e.g. epilepsy, which may interfere with study treatment or effect evaluation.

 Pregnancy (or risk of pregnancy).

 Subject has prior to randomization received prophylactic treatment with lithium or lamotrigine conducted adequately in the sense of sufficient time and dose and ensuring compliance, and experienced a definite lack of prophylactic effect

 An ICD-10 diagnosis of abuse within the last year with a subsequent risk of protocol violation. Therefore, subjects with a secondary abuse can often be included in the study.

 Anticipated protocol violation for other reasons.

 No written informed consent from the subject can be obtained.

 The subject has previously been randomised in the study.


SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors

Summary: Brain tumours are the commonest solid tumours in children and the second most common neoplasms overall in this patient population. Radiotherapy plays an important part in the management in a majority of these tumours. While the cure rates of these tumours, especially the benign and low grade ones are quite encouraging, the treatment itself may lead to some late sequelae, which could have significant implications in the quality of life in these long-term survivors.~Stereotactic conformal radiotherapy (SCRT) is a modern high-precision radiotherapy technique, which reduces the volume of normal brain irradiated and has the capability to minimise the doses to critical structures. The present study is designed to prospectively estimate the incidence and severity of neuropsychological, cognitive and neuroendocrine dysfunction following radiotherapy delivered with conventional and stereotactic techniques and would be one of the most comprehensive studies providing very important longitudinal and reliable data regarding these sequelae. The study involving 200 patients would be to the best of our knowledge not only the largest ever study conducted so far but also the only randomised trial assessing these sequelae in patients receiving focal brain irradiation.~The study also examines whether the physical advantages of modern technological progress translate in clinical benefit. This could have significant implications in the radiotherapeutic management of children and young adults with brain tumours. The study is unique in design in terms of evaluating the efficacy of SCRT with respect to conventional radiotherapy in terms of long term tumour control and treatment related complications.
Inclusion criteria: inclusion criteria:

 Patients with primary intracranial tumours such as low-grade glioma, meningioma, craniopharyngiomas, ependymomas and other benign tumours considered for radical focal radiotherapy.

 Tumours measuring upto 7 cms on maximum dimension on the CT/MRI.

 Age 3 to 25 years.

 NPS of 0-3.

 Informed consent from patients or parents as appropriate.

 Long-term follow up expected

Exclusion criteria: :

 Previous radiotherapy.

 Planned adjuvant chemotherapy.

 Expected median survival of less than two years.

 Patient not cooperative for planning and execution of SCRT.

['Stereotactic Conformal radiotherapy', 'Conventional radiotherapy']

Stereotactic Conformal radiotherapy
Conventional radiotherapy

['Low Grade Gliomas', 'Craniopharyngioma', 'Ependymomas', 'Meningiomas']

Low Grade Gliomas
Craniopharyngioma
Ependymomas
Meningiomas


Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD.

Summary: The Compare-Acute trial is a prospective randomised trial in patients with multivessel disease, who are admitted into hospital with a ST-elevation Myocardial Infarction. The purpose of the study is to compare a FFR guided multivessel PCI taking place during the primary PCI with a primary PCI of the culprit vessel only.~Patients will be enrolled after successful revascularisation of the culprit vessel. Patients that have at least one lesion with a diameter of stenosis of more than 50% on visual estimation, feasible (operators judgement) for treatment with PCI in a non-infarct related artery, will be randomised either to the FFR guided complete revascularisation arm or staged revascularisation by proven ischemia or persistence of symptoms of angina.~Approximately 885 patients will be entered in the study.~Study hypothesis: FFR-guided complete percutaneous revascularisation of all flow-limiting stenoses in the non-IRA performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to the staged revascularisation, guided by prove of ischemia or clinical judgment, as recommended from the guidelines.
Inclusion criteria: inclusion criteria:

 All patients between 18-85 years presenting with STEMI who will be treated with primary PCI in < 12 h after the onset of symptoms* and have at least one stenosis of >50% in a non-IRA on QCA or visual estimation of baseline angiography and judged feasible for treatment with PCI by the operator.

 Patients with symptoms for more than 12 hr but ongoing angina complaints can be randomised

Exclusion criteria: :

 Left main stem disease (stenosis > 50%)

 STEMI due to in-stent thrombosis

 Chronic total occlusion of a non-IRA

 Severe stenosis with TIMI flow ≤ II of the non-IRA artery.

 Non-IRA stenosis not amenable for PCI treatment (operators decision)

 Complicated IRA treatment, with one or more of the following;

 Extravasation,

 Permanent no re-flow after IRA treatment (TIMI flow 0-1),

 Inability to implant a stent

 Known severe cardiac valve dysfunction that will require surgery in the follow-up period.

 Killip class III or IV already at presentation or at the completion of culprit lesion treatment.

 Life expectancy of < 2 years.

 Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, Bivaluridin, or Everolimus and known true anaphylaxis to prior contrast media of bleeding diathesis or known coagulopathy.

 Gastrointestinal or genitourinary bleeding within the prior 3 months,

 Planned elective surgical procedure necessitating interruption of thienopyridines during the first 6 months post enrolment.

 Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.

 Pregnancy or planning to become pregnant any time after enrolment into this study.

 Inability to obtain informed consent.

 Expected lost to follow-up.

['FFR-guided revascularisation strategy', 'randomised to guidelines group']

FFR-guided revascularisation strategy
randomised to guidelines group

['Myocardial Infarction', 'Multivessel Coronary Artery Disease']

Myocardial Infarction
Multivessel Coronary Artery Disease


High-Field MRI Characterization of Wrist and Hand Cartilage Abnormalities in Inflammatory and Chronic Rheumatisms

Summary: The present project aims at evaluating the diagnostic potential of high-field MRI (3 Teslas) for joint disease. At this field, given that isotropic image resolution of 400 microns can be obtained, one could expect an early detection of joint abnormalities. The additional aim of this project will be to develop a quantitative analyse of the corresponding high-resolution images.
Inclusion criteria: inclusion criteria:

 gp Suspects or affected by rheumatoid polyarthritis

 Morning articular Stiffness of at least 15 minutes.

 Arthalgias or Arthritises of at least three joints(articulations), among which those of the hand.

 Possible rheumatoid Presence of a factor(mailman) and\or Antibody anti peptides positive citrullinés.

 Typical possible radiological Hurts on the standard clichés(pictures) of the reached(affected) joints(articulations).

 gp Affected by stiffening spondylitis with axial and peripheral infringement :

 . Lumbago and steepness lumbar vertebra inflammatory. 2. Arthralgias and\or peripheral arthritises 3. Possible presence of an allèle HLA 4. Possible presence of a sacro-illite 5. Absence of the other rheumatic markers

 gp Affected by connectivity with anti-nuclear antibody positive and / or specific antibodies, suffering of polyarthralgias with or without arthritis

 gp Healthy control

 gp Presenting a degenerative osteoarthritis of the wrist traumatic comment, noticed radiologically, which will serve as not inflammatory control.

Exclusion criteria: :

 Claustrophobia,

 metallic foreign bodies,

 pacemakers The pregnant women,

 parturients or who breast-feed are excluded from the study

['high-field MRI (3 Teslas)', 'high-field MRI (3 Teslas)', 'high-field MRI (3 Teslas)', 'high-field MRI (3 Teslas)']

high-field MRI (3 Teslas)
high-field MRI (3 Teslas)
high-field MRI (3 Teslas)
high-field MRI (3 Teslas)


Airway Inflammation and Bronchial Hyperresponsiveness in Rhinitic Children With or Without Asthma

Summary: This is a prospective observational study , to clarity the characteristics of airway inflammation, airway reactivity and airway resistance in rhinitic children with or without asthma and to explore the possible predictors in the progression of allergic rhinitis to asthma.
Inclusion criteria: inclusion criteria:

 Clinical diagnosis of allergic rhinitis and/or asthma

 Sensitized to more than 1 common aeroallergens

Exclusion criteria: :

 Respiratory infection 2 weeks prior to initial visit

 Children with nasal polyposis

 History of immunotherapy

 Unable to complete the test or had limited understanding

 Use of systemic corticosteroids 4 weeks prior to initial visit

 Nasal and inhaled corticosteroids 2 weeks prior to initial visit

 Leukotriene receptor antagonists 2 weeks prior to initial visit

['Rhinitis', 'Asthma', 'Inflammation', 'Hypersensitivity']

Rhinitis Asthma Inflammation Hypersensitivity


Monitoring of Tissue Transfer Flaps by Modulated Imaging (MI) Spectroscopy

Summary: Tissue transfer flaps are a method of moving tissue from a donor location to a recipient location. In the case of a free tissue transfer flaps, the blood vessels to the transferred tissues are detached and then re-attached to different arteries & veins at the recipient site. The process of reconstructive surgery using tissue transfer flaps allows for improved results in terms of functionality, aesthetic appearance, and psychological well-being in patients requiring reconstructive surgery after cancer resection or trauma. The process of reconstructive surgery using tissue transfer flaps is not without complications. These complications may include acute arterial or venous occlusion, as well as the development of late complications such as fat necrosis and flap atrophy.~The purpose of this pilot study is to determine if a novel, unique, portable, non-contact optical imaging device developed at the Beckman Laser Institute called Modulated Imaging (MI) can detect changes in a flap's optical properties, which can correlate with arterial or venous occlusion or with the development of fat necrosis or flap atrophy. The study would also evaluate if changes in the tissue transfer flap's optical properties, as detected by the device could be employed as a monitoring device in the post-operative period after reconstructive surgery. The MI device's detection of specific optical properties of a tissue flap could also potentially be used as a diagnostic tool to predict the likelihood of the development of fat necrosis or flap atrophy in a delayed fashion several months after reconstructive surgery.~Prior animal and clinical studies using similar devices have demonstrated that changes in the total hemoglobin concentration and percentage of oxygenated hemoglobin in the tissue transfer flap can be used to differentiate between arterial and venous occlusion. These other similar devices have been shown to be able to detect venous occlusion prior to clinical manifestations of venous occlusion using standard monitoring methods. This early detection of venous occlusion has important implications. It is well established that early detection and surgical re-exploration and correction of venous occlusion is associated with improved survival and salvage rates of tissue transfer flaps. It has been suggested in the reconstructive literature that the development of fat necrosis and flap atrophy are caused by a relative arterial or venous insufficiency, which could be detected using the MI device prior to the clinical manifestations of these complications.Patients undergoing reconstructive surgery at UCI Medical Center will be recruited for enrollment into the study. The study design requires following the patients and review their medical records in order to determine the clinical outcomes of their reconstructive surgery. The process of review of the medical record will require the review of both the in-patient medical record during the hospitalization in which the reconstructive surgery takes place and the outpatient medical record after surgery in order to observe for the possible development of the acute and delayed complications of reconstructive surgery.
Inclusion criteria: inclusion criteria:

 Adult patients planned to undergo reconstructive surgery using either a pedicle or free tissue transfer flap seen by The Plastic Surgery Service on either an in-patient or outpatient bases.

 Adult patients that are planned to undergo reconstructive surgery as above and able to receive information regarding the study and provide informed consent to enrollment in the study.

Exclusion criteria:

 All emergency reconstructive surgery patients.

 Patients planned to undergo radiation therapy in the region of the reconstructive surgery within 6 months after surgery.

 Patients who develop hypotension requiring the administration of vasopressors either intra-operatively or during the post-operative period prior to discharge from the hospital.

 Patients who develop clinical signs of a surgical site infection at the location of the tissue transfer flap(s).

 Patients with the development of post-operative anemia requiring a blood transfusion during the first 72 hours after surgery.

 Patients with tattooing or pigmented lesions on the tissue transfer flap.

 Patients who incur injury to the flaps secondary to trauma within 6 months of the reconstructive surgery; with trauma defined as either accidental major trauma resulting in injury to the tissue transfer flap or surgical trauma as a result of further oncologic resection of tissues in close proximity to the tissue transfer flap.

 Minor under the age of 18 years of age.

 Patients deemed unable to comprehend and provide informed consent to enrollment into study due to either a cognitive deficit or medical condition.

['Reconstructive Surgical Procedures', 'Tissue Transplantation']

Reconstructive Surgical Procedures
Tissue Transplantation


Pelvic CT Imaging in Blunt Abdominal Trauma

Summary: Abdominopelvic CT (CTap) utilization rose significantly in blunt trauma patients over the last decade. However, the observed increases failed to reduce mortality or missed injury rates. Several investigators have derived (citation) and validated (citation) clinical decision rules that attempt to identify a subset of low risk pediatric and adult patients in whom abdominopelvic CT imaging can be safely eliminated. Thus far these efforts failed to significantly reduce utilization. The investigators propose an alternative and complimentary strategy to decrease radiation by selectively eliminating the pelvic imaging portion of the abdominopelvic CT in low risk patients. In stable, alert patients without clinically evidence of pelvis or hip fractures, abdominal CT imaging alone (diaphragm to iliac crest) identifies clinically significant intra-abdominal injury (cs-IAI) as accurately as routine abdominopelvic imaging (diaphragm to greater trochanter) and results in a clinically important decrease in radiation exposure. The study will investigate this by comparing the accuracy of an imaging protocol using CT abdomen alone versus CT abdomen and pelvis to detect cs-IAI among stable, blunt trauma patients without suspected pelvis or hip fractures in two age groups: ages 3-17 years and 18-60. Patients will undergo CT imaging as deemed clinically indicated by the treating clinician. Among those who have abdominopelvic CT scans, the study will determine the test characteristics of CT abdomen alone versus CT abdomen plus CT pelvis imaging for the identification of cs-IAI. The reference standard will include initial radiology reports, with structured follow up of indeterminate scans, operative reports, and 7-day medical record review.
Inclusion criteria: inclusion criteria:

 3-60 years of age evaluated for blunt trauma with a GCS of >14

 Order of CT abdomen and pelvis imaging

Exclusion criteria: :

 Patients requiring intubation or suspected neurological injury (defined above)

 Pregnant patients

 Intoxicated patients

 Patients with age defined hypotension

 Exploratory laparotomy or transfusion during the ED evaluation

 Non-verbal patients

 Positive FAST exam

 Patients with abdominal trauma or surgery in the last month

 Victims of sexual assault or non-accidental trauma (NAT)

 Patients with known or suspected fractures of the femur or pelvis prior to CT imaging

 Patients with hip dislocations


The Role of Partial Reinforcement in the Long Term Management of Insomnia

Summary: The lack of scientific attention devoted to the placebo effect as a phenomenon in its own right probably reflects the paucity of theoretical positions within which to organize the existing data and design new research. The proposed investigation 1) is an attempt to advance from a descriptive to an experimental analysis of the placebo effect, taking into account classical conditioning effects, and 2) examines the clinical implications of partial reinforcement as it is applied to the treatment of insomnia. Subjects with primary insomnia will be treated with zolpidem for a period of one month and then randomized to one of four groups for a period of 12 weeks: one receiving full dose zolpidem on a nightly basis (continuous reinforcement), one receiving full dose zolpidem on 14 of 28 nights where placebo is provided on non-drug nights (partial reinforcement), one receiving full dose zolpidem on 14 of 28 nights where no pills are imbibed on non-drug nights (intermittent dosing), and one receiving 5 mg dose zolpidem on a nightly basis (continuous reinforcement with half the standard dose). Following treatment, subjects will be entered into an extinction protocol during which they will 1) continue on the schedule assigned during the experimental period, 2) receive only placebo, or 3) receive neither drug nor placebo. Sleep and daily functioning will be monitored on a daily basis via sleep diaries for the duration of the study. It is hypothesized that, holding cumulative dose constant, a partial schedule of reinforcement will enable patients to better maintain their clinical gains as compared to subjects that receive either continuous reinforcement with half the standard dose or half the frequency of use.~Relevance: The proposed research is not an attempt to offer a behavioral alternative to drug treatment; it is an attempt to acknowledge and capitalize on a behavioral dimension in the design of drug treatment protocols. The value of the proposed research resides in its capacity to provide for the long term treatment of insomnia in a manner that increases the durability of pharmacotherapy while reducing the overall amount of medication required. If proven effective in the current application, this new approach to pharmacotherapy and placebo effects is likely to stimulate new interdisciplinary research for the treatment of a variety of chronic diseases.
Inclusion criteria: inclusion criteria:

 Patients with insomnia will meet RDC criteria for psychophysiologic insomnia(99). These criteria are provided in Appendix 2. In addition, the complaint of disturbed sleep will have one or more of the following characteristics:

 > 30 minutes to fall asleep (Initial Insomnia)

 2 awakenings per night of >15 minutes duration and/or wake after sleep onset time of > 30 minutes (Middle Insomnia)

 An awakening of > 30 minutes prior to the desired wake up time (Late Insomnia)

 Any two of the above complaints (Mixed Insomnia)

 Additionally, total sleep time will not exceed 6 hours (unless the sleep efficiency quotient is < 80%) and the problem frequency must be equal to or greater than 4 nights/ week (severe insomnia) with a problem duration > 6 months (chronic insomnia). This profile must be evident at both intake (based on retrospective reports) and as an average profile from the two weeks of baseline diaries (based on prospective sampling).

Exclusion criteria: :

 Unstable medical or psychiatric illness Assessed with the Mini International Neuropsychiatric Interview (MINI) and the The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) To assure that the insomnia is not secondary to these factors

 Symptoms suggestive of sleep disorders other than insomnia Assessed with the SDS-CL To assure that the insomnia is not secondary to these factors

 Polysomnographic data indicating sleep disorders other than insomnia Assessed with PSG in collaboration with our sleep medicine consultants To assure that the insomnia is not secondary to these factors

 History of head injury with a sustained loss of consciousness Assessed by self report during the Intake Interview To help assure that the EEG measures are unconfounded by brain damage

 Evidence of active illicit substance use or fitting criteria for alcohol abuse or dependence Assessed with a structured psychiatric interview schedule (the MINI) , written versions of clinical interview queries regarding alcohol use, abuse and dependence (the AUDIT and CAGE), the toxicology screen which is part of the clinical chemistries obtained during the screening physical. To assure that the insomnia is not secondary to these factors and to assure that substance use/abuse does not confound treatment.

 Use of CNS active medications, antidepressants, and hypnotics other than zolpidem Assessed by self report and from the toxicology screen which is part of the clinical chemistries obtained during the screening physical. To help assure that the clinical effects observed in this study are due to the study medication and schedule of reinforcement.

 Inadequate language comprehension Informally, assessed by the Clinical Research Coordinator during Intake Interview To assure the quality of self report data as all the measures are in English.

 Pregnancy Assessed by self report and from the clinical chemistries data obtained during the screening physical. Excluded so as to 1) prevent the fetus from exposure to the study medication (although it should be noted that the medication is considered FDA pregnancy category B) and 2) control for the biopsychosocial changes that occur with pregnancy and may alter the response to the study medication and schedule of reinforcement.

 No first-degree relatives with bipolar disorder or schizophrenia Assessed by self report and a structured psychiatric interview schedule (the SADs). Excluded to reduce risk for first onset during the study


Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF)--A Single Center Pilot Study.

Summary: The primary objective of the study is to determine efficacy of metolazone as synergistic therapy with Lasix in patients with acute decompensated heart failure. This will be a single center double blinded randomized placebo- controlled pilot study of the addition of 5 mg of metolazone per day for 2 days compared to placebo in patients admitted with acute decompensated heart failure.
Inclusion criteria: inclusion criteria:

 Age 18 years or older

 Current hospitalization for chronic congestive heart failure with admission up to 48 hours prior to inclusion.

 Chronic heart failure will be defined as requiring treatment for a minimum of 30 days prior to current admission, NYHA Class III or IV at the time of hospitalization, and left ventricular ejection fraction less than 40% within one year or evidence of heart failure with preserved ejection fraction and evidence of diastolic dysfunction on echocardiogram.

 Admitted with clinical decompensated heart failure based on history, physical exam, and parameters indicating extracellular volume expansion such as including JVP ≥ 8 cm of water and 1+ or greater peripheral edema

 Is able to be dosed with study medication within six (6) hours of first dose of IV diuretics

Exclusion criteria: :

 Baseline severe hypotension (Mean arterial pressure < 55 mm Hg)

 Creatinine clearance less than 20 ml/min or creatinine greater than 2.5 mg/dl.

 Serum sodium less than 128 meq/L.

 Serum Potassium < 3.0 meq/L.

 Known adverse reaction to metolazone

 Inability to take oral medications

 Severe Aortic Stenosis (AVA < 0.8cm2)

 History of Hypertrophic obstructive cardiomyopathy

 Metastatic Carcinoma per history

 Severe COPD, FEV < 1L

 Severe dyspnea requiring prolonged CPAP,BIPAP or intubation

['Experimental: Placebo', 'Experimental: Metolazone']

Experimental: Placebo
Experimental: Metolazone