An Effectiveness Study Comparing Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) With Standard Treatment in Asthma

Summary: This study is designed to compare the effectiveness and safety of Fluticasone Furoate/Vilanterol Inhalation Powder (100mcg Fluticasone Furoate ((FF), GW685698)/25mcg Vilanterol ((VI), GW642444) or 200mcg Fluticasone Furoate ((FF), GW685698)/25mcg Vilanterol ((VI), GW642444) ) delivered once daily via a Novel Dry Powder Inhaler (NDPI) compared with the existing asthma maintenance therapy over twelve months in subjects diagnosed with asthma. This is a Phase III multi-centre, randomised open label study. Subjects who meet the eligibility criteria are randomised and will enter a 12 month treatment period.
Inclusion criteria: inclusion criteria:

 Subjects eligible for enrolment in the study must meet all of the following criteria:

 Informed consent: Subjects must be able to provide informed consent, have their consent signed and dated.

 Type of subject: Subjects with documented GP diagnosis of asthma as their primary respiratory disease.

 Current Anti-Asthma Therapy: All subjects must be prescribed maintenance therapy and receiving ICS with or without LABA (either a fixed combination or via separate inhalers), and for at least 4 weeks prior to Visit 2.

 Other background asthma medication such as anti-leukotrienes are permitted

 All subjects on ICS monotherapy or ICS/LABA combination (this can be a fixed dose combination or an ICS alone or LABA alone in separate inhalers) must have had symptoms in the past week prior to Visit 2. Symptoms are defined by daytime symptoms more than twice per week, use of short-acting beta2-agonist bronchodilator more than twice per week, any limitation of activities, or any nocturnal symptoms/awakening. (The symptoms are based on subject's recall and are consistent with the GINA and in principal with the BTS/SIGN guidelines).

 Subject questionnaires: Subjects must be able to complete the electronic subject questionnaires as well as those questionnaires that are completed by phone or provide a proxy e.g. a partner/relative/a friend who can do so on their behalf

 Gender and Age: Male or female subjects aged ≥18 years of age at Visit 1. A female is eligible to enter and participate in the study if she is of:

 Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However in questionable cases, a blood sample with FSH > 40MIU/ml and estradiol <40pg/ml (<147 pmol/L) is confirmatory.

 OR Child bearing potential has a negative urine pregnancy test at Visit 2, and agrees to one of the highly effective and acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - Visit 2 to the end of the study).

Exclusion criteria: :

 Subjects meeting any of the following criteria must not be enrolled in the study:

 Recent history of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 6 months.

 COPD Respiratory Disease: A subject must not have current evidence or GP diagnosis of chronic obstructive pulmonary disease.

 Other diseases/abnormalities: Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the GP/ Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.

 Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g., beta2-agonists, corticosteroid) or components of the inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the GP/ Investigator, contraindicates the subject's participation will also be excluded.

 Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 2 or within five half-lives (t½) of the prior investigational study (whichever is longer of the two), (if unsure discuss with the medical monitor prior to screening)

 Chronic user of systemic corticosteroids: A subject who, in the opinion of the GP/Investigator, is considered to be a chronic user of systemic corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening)

 Subjects who are using LABA without an ICS as asthma maintenance therapy.

 Subjects who plan to move away from the geographical area where the study is being conducted during the study period and/or if subjects have not consented to their medical records being part of the electronic medical records database that is operational in the Salford area.

['fluticasone furoate + vilanterol', 'inhaled corticosteroid with or without a long acting beta2-agonist']


Sleep Apnoea Syndrome Without Chronic Heart Failure

Summary: It is the objective of this study to collect scientific data of sleep apnoea syndrome patients´ cardiac and respiratory function by additional sensors.
Inclusion criteria: inclusion criteria:

 patients with supected sleep apnoea syndrome and scheduled diagnosis at a sleep laboratory

 male and female patients aged at least 18 years

 persons who understand and follow the instructions of the study staff

 singed informed consent

Exclusion criteria: :

 persons being housed in an institution by court or governmental order

 pregnancy or breastfeeding

 patients who are not able to consent

 acute or chronic inflammations of the external and middle auditory canal

 abnormal anatomic proportionsof the external and middle auditory canal which are pathological or congenital, for example limitation of the auditory canal

 persons in a dependence or in an employment contract to the investigator

 participation in another study at the same time


Efficacy of Euminz® for Tension-Type Headache

Summary: Efficacy and safety of Euminz® (10% ethanolic solution of peppermint oil for topical use) compared to placebo in patients with episodic tension-type headache (ETTH).~Prospective, double-blind, placebo-controlled, phase IV clinical trial; Parallel-groups design; Randomisation 1:1; First attack per patient will be evaluated for primary objectives, following attacks during study duration will be observed and documented.~Study duration per patient: 10 weeks
Inclusion criteria: inclusion criteria:

 Male and female patients from 18 years onwards

 History of ETTH for at least one year. The number of days with such a headache is ≥2 per month

 Onset of TTH below 65 years of age

 At least 10 previous headache attacks fulfilling the following four inclusion criteria:

 Patients with headache attacks lasting from 30 minutes to 7 days

 At least two of the following pain characteristics are present:

 - Pressing or tightening (non-pulsating) quality

 - Intensity of pain: moderate = unable to ignore (pain may inhibit, but does not prohibit activities)

 - Bilateral location

 - No aggravation by walking stairs or similar routine physical activity

 Headache is not accompanied by nausea or vomiting (anorexia may occur)

 Headache is not accompanied by a combination of the following symptoms: photophobia and phonophobia (only one may be present)

 3 months retrospective history

 Willingness and ability to keep the patient's diary and to comply with the procedures of the study

 Written informed consent

Exclusion criteria: :

 Headaches other than TTH: (e.g. migraine, cluster headache, hypertension headache, drug-related headache,analgesic-induced headache,post-traumatic headache; associated migraine attacks are permitted if they are well recognized by the patient and if their frequency during the preceding year has not exceeded one per month)

 Presence of oromandibular dysfunction

 History of facial or cranial surgery

 Use of prophylactic drugs for headache within one month prior to enrolment

 Use of drugs for acute TTH treatment for ≥ 10 days of headache per month

 Anticipated problems in adhering to the self-observation procedure (e.g. because of work)

 Abuse of alcohol, narcotics or other drugs

 Serious illnesses within the last 3 months (e.g. myocardial infarction, cardiac insufficiency NYHA III and IV, low blood pressure, cerebral insult, diabetes mellitus, neuropathy, changes in the skin or neoplasms in the head)

 Epilepsy

 Intake of anti-psychotic, anti-depressant or anti-epileptic medication during the previous month

 Intake of long-acting non-steroidal anti-inflammatory drugs within the last month

 Planned start of new pharmacological or non-pharmacological therapies

 Any significant skin condition affecting face or neck

 Known hypersensitivity towards peppermint oil

 Previous use of Euminz® or any other essential oil solutions for headache in the last three months

 Participation in another clinical trial within the last month

 Accommodation in an institution at judicial or official request


Comparative Effectiveness of Adding Weight Control to Smoking Cessation Quitlines

Summary: This randomized controlled trial compares the effectiveness for both smoking cessation and weight control of two alternative combined interventions offered via telephone quitline, as compared to standard of care quitline treatment addressing cessation alone. The interventions to be compared are cessation treatment alone versus cessation treatment combined with weight control treatment added either simultaneously or sequentially.
Inclusion criteria: inclusion criteria:

 Participating Client

 Not Re-Enrolling

 USA Resident

 Wants to quit in the next 30 days

 Use Cigarettes (other types ok, but must use cigarettes)

 18 years or older

 Speak English

 Provide Phone

 Provide Email Address

 Use 10 cigarettes per day or more

 BMI of 18.5 or above

 No history of anorexia or bulimia

Exclusion criteria: :

 Pregnant or Planning Pregnancy within 3 months

 Diabetic

 Previous weight loss surgery or planning weight loss surgery in next 12 months

['Weight gain prevention and smoking cessation', 'Smoking cessation']

['Cigarette Smoking', 'Overweight', 'Obesity']


BES, EES, and ZES-R in Real World Practice

Summary: The primary objective of this study is to compare the rate of device-oriented composite consisted of cardiac death, myocardial infarction not clearly attributable to a nontarget vessel, and clinically indicated target lesion revascularization among the patients treated with EES, ZES-R, or BES at 24-month clinical follow-up post-index procedure. Trial end points are summarized in Table I. The hypothesis is that BES is equivalent to EES or BES is equivalent to ZES-R at the primary end point.
Inclusion criteria: inclusion criteria

 Age > 19 years

 Subject is able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving the drug-eluting stent(s) and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure

 Subject must have significant stenosis (>50% by visual estimate) on a native or in-stent coronary artery

 Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, recent infarction, acute myocardial infarction, positive functional study or a reversible changes in the ECG consistent with ischemia). In subjects with coronary artery stenosis >75%, evidence of myocardial ischemia does not have to be documented

Exclusion criteria:

 Subject has a known hypersensitivity or contraindication to any of the following medications: heparin, aspirin, clopidogrel, prasugrel, ticagrelor, biolimus A9, everolimus, zotarolimus, stainless steel, cobalt chromium, contrast media (Patients with documented sensitivity to contrast media, which can be effectively premedicated with steroid and diphenhydramine may be enrolled. However, those with true anaphylaxis to prior contrast media should not be enrolled.)

 Subject in use of systemic (intravenous) biolimus A9, everolimus or zotarolimus within 12 months.

 Female subject of childbearing potential, unless a recent pregnancy test is negative, who possibly plans to become pregnant any time after enrollment into this study

 Subject planned an elective surgical procedure that would necessitate interruption of antiplatelet during the first 12 months post enrollment

 Subject with non-cardiac co-morbid condition with life expectancy < 2 year or that may result in protocol non-compliance (per site investigator's medical judgment)

 Subject with cardiogenic shock at presentation

 Subject who are actively participating in another drug or device investigational study, who have not completed the primary end point follow-up period

['Biolimus-eluting stent', 'Everolimus-eluting stent', 'Zotarolimus-eluting stent']

Biolimus-eluting stent
Everolimus-eluting stent
Zotarolimus-eluting stent


Honolulu Heart Program

Summary: To investigate coronary heart disease and stroke among American men of Japanese ancestry who were living on the island of Oahu in 1965. Morbidity and mortality surveillance of the original cohort is continuing.
Inclusion criteria: No eligibility criteria
Exclusion criteria:

['Cardiovascular Diseases', 'Coronary Disease', 'Cerebrovascular Accident', 'Heart Diseases', 'Heart Failure, Congestive', 'Myocardial Infarction', 'Asthma', 'Emphysema', 'Lung Diseases, Obstructive', 'Aortic Aneurysm, Abdominal', 'Bronchitis', 'Dementia', 'Hypertension', 'Chronic Obstructive Pulmonary Disease', 'Heart Failure']

Cardiovascular Diseases
Coronary Disease
Cerebrovascular Accident
Heart Diseases
Heart Failure
Congestive
Myocardial Infarction
Asthma
Emphysema
Lung Diseases
Obstructive
Aortic Aneurysm
Abdominal
Bronchitis
Dementia
Hypertension
Chronic Obstructive Pulmonary Disease
Heart Failure


Searching for Persistence of Infection in Lyme Disease

Summary: Background:~Lyme disease is an infection caused by Borrelia burgdorferi, a bacteria that is transmitted to humans by ticks. It can cause many different symptoms including rash, fever, headache, meningitis (infection of the central nervous system), and arthritis. While most patients improve after taking antibiotics, some patients continue to have symptoms. It is currently unknown why some patients continue to have symptoms. One possibility is that the antibiotics have not successfully gotten rid of all of the bacteria. Current tests for Lyme disease cannot tell whether the bacteria have been successfully eliminated from the body.~Xenodiagnosis is a way to look for Borrelia bacteria using the animal that usually hosts them, Ixodes scapularis (also known as the deer tick). This method takes advantage of the evolution of the bacteria and the insect that transmits the infection, which can make the insect particularly good at finding the agent. In studies of animals, xenodiagnosis may be more sensitive than current tests for detecting the presence of the Lyme disease bacteria. Researchers are interested in using xenodiagnosis to determine whether uninfected ticks that feed on humans who have been infected with Lyme disease bacteria can detect the continued presence of live bacteria.~Objectives:~- To determine whether xenodiagnosis can be used to successfully investigate the presence of Lyme disease bacteria.~Eligibility:~Individuals at least 18 years of age who are in one of the following categories:~Have had the erythema migrans rash (a symptom of Lyme infection) and received antibiotic therapy less than 4 months ago (but have not had antibiotics in the previous month).~Have the erythema migrans rash and received less than 2 days of antibiotic therapy.~Have been diagnosed with early or late Lyme disease, have received antibiotic therapy, but still have high levels of antibodies against the bacteria at least 6 months after therapy, and have not received antibiotics in the past 3 months.~Have been diagnosed with early or late Lyme disease, have received antibiotic therapy, and have new complaints of fatigue or other symptoms that are persistent for at least 6 months after completion of antibiotic therapy, and have not received antibiotics in the past 3 months.~Have been diagnosed with Lyme arthritis and have not yet received antibiotic therapy.~Healthy volunteers who have not had Lyme disease will also be included in this study.~Design:~Participants will have an initial visit for a physical examination, medical history, and blood sample.~For the first study visit, researchers will place a strip of filter paper or a small plastic container with 20 to 30 disease-free ticks on the participant s skin. If possible, the ticks will be placed at the site of a Lyme disease rash or another suspicious area, or on the nondominant forearm. Participants will be asked to keep the ticks in place, and will keep a diary card at home to record any symptoms or problems.~The ticks will be collected 4 to 6 days after placement. At that visit, participants will have a skin biopsy taken of the area tested, a blood sample will be collected, and participants will receive a new diary card to keep until the next clinic visit.~After 1 month, participants will provide a final blood sample, and will receive a follow-up phone call 2 months afterward.
Inclusion criteria: inclusion criteria:

 Criteria for the diagnosis of Lyme disease can be found at The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America (4).

 Patients With EM (N=35), Post Treatment

 Age 18 or older

 EM diagnosed by the study physician or, with a diagnosis of EM that is thought to be highly likely by the study physician.

 Treatment with at least 1 course of antibiotics that fulfills the Infectious Diseases Society of America guidelines for the recommended therapy for Lyme disease. There must be at least 1 month and up to 4 months between the end of the therapy and the study procedures.

 High C6 Antibody Titer (N=35)

 Age 18 or older

 Diagnosed with confirmed or probable early or late Lyme disease as per Centers for Disease Control and Prevention (CDC) case definition (http://www.cdc.gov/ncphi/disss.nndss/caseded/lyme disease 2008.htm), have received recommended antibiotic therapy and have a high C6 ELISA titer (index above 3) at least 6 months after therapy.

 Post Lyme disease syndrome (N=20)

 Age 18 or older

 Diagnosed with confirmed or probable early or late Lyme disease fulfilling the case definition of Lyme disease by the CDC (http://www.cdc.gov/ncphi/disss.nndss/caseded/lyme disease 2008.htm)

 Received recommended antibiotic therapy, with resolution or stabilization of the objective manifestation(s) of Lyme disease.

 New complaints of fatigue, paresthesias or dysesthesias, widespread musculoskeletal pain or cognitive difficulties within 6 months of the diagnosis of Lyme disease

 Symptoms are persistent or relapsing for at least a 6-month period after completion of antibiotic therapy, causing reduction in previous levels of occupational, educational, social, or personal activities.

 No antibiotic therapy active against Lyme disease in the previous 3 months.

 Patients With EM (N=20), On Treatment

 Age 18 or older

 EM diagnosed by the study physician and receiving antibiotic therapy for less than 48 hours.

 Lyme Arthritis (N=10)

 Age 18 or older

 Lyme arthritis and have not received therapy.

 Healthy Volunteers (N=30)

 Age 18 or older

 No history of Lyme disease

 Negative whole-cell Borrelia ELISA or C6 ELISA

 Living in an endemic area for Lyme disease.

Exclusion criteria: :

 History of allergy to surgical tape or Nitex nylon mesh

 History of severe reactions to tick bites (granuloma or systemic reactions)

 Inability to maintain the dressing for any reason

 Currently receiving any antibiotic or having received antibiotics in the last month (3 months for patients with post Lyme disease syndrome and high C6 titer) (except patients with EM on treatment)

 Pregnancy or lactation

 Unwillingness to use an effective method of birth control for 3 months after tick placement (women of child-bearing potential only)

 Not able to understand all of the requirements of the study or unable to give informed consent and/or comply with all aspects of the evaluation.

 Investigational therapy during the time of the study and/or in the month prior to signing the informed consent.

 Active severe skin disease, uncontrolled diabetes, cancer other than non-melanoma skin cancers, autoimmune disease requiring immunosuppressive therapy, or history of HIV, chronic viral hepatitis, or syphilis.

 Oral steroids in the previous 2 weeks (nasal steroids and replacement doses of steroids are not exclusions)

 Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in and completing the study.

 EXCLUSION FROM SKIN BIOPSY PART OF THE PROTOCOL:

 History of forming large thick scars after skin injuries or surgery

 History of excessive bleeding after cuts or procedures

 Currently taking anticoagulants

 History of allergy to lidocaine

 Biopsies will not be done on face, neck, scalp, or over the tibia


Prevention of Severe Anaemia in Gambian Children

Summary: Severe anaemia is a frequent cause of admission to hospitals in tropical Africa and about 10% of such children die. In endemic countries, anaemia has multiple causes such as nutritional deficiencies, infections and haemoglobinopathies. However, Plasmodium falciparum infection is believed to be the major contributory factor to the aetiology of severe anaemia. Severe anaemia is usually treated by blood transfusion although transfusion carries the attendant risk of transmission of HIV and other blood-borne infections. Thus, there is a need to explore novel strategies to reduce the incidence of severe anaemia in high-risk groups such as children with suboptimal haemoglobin levels because these children are at increased risk of developing severe anaemia if they develop a malaria infection before their haemoglobin level has normalized. Therefore, it is proposed to study whether monthly chemoprophylaxis with sulphadoxine/pyrimethamine (S/P) given during malaria transmission season can protect Gambian children from developing severe anaemia. After receiving treatment from the hospital, 1200 children admitted to the hospital with a haematocrit of less than 21% were randomised to receive either monthly S/P or placebo during the rest of the malaria transmission season. Morbidity was monitored throughout the rainy season. Study subjects were seen at the end of the dry season to document morbidity and mortality.
Inclusion criteria: inclusion criteria:

 Age: 3 months to 9 years.

 Haemoglobin concentration 7g/dl on admission to hospital.

 Residence within 30 km of the study centre and availability for the duration of the study period.

 Informed consent to participate in the study given by the parent or guardian.

Exclusion criteria: :

 Simultaneous participation in any other trial.

 Allergy to sulpha drugs.

 Residence > 30 km from the recruitment site.

 Lack of consent.


Aripiprazole in the Treatment of Patients With Psychosis Associated With Dementia of Alzheimer's Type

Summary: The primary objective of the study is to compare the efficacy of aripiprazole with placebo in patients with psychosis associated with Alzheimer's dementia.
Inclusion criteria: inclusion criteria:

 Non-institutionalized patients with a diagnosis of Alzheimer's disease as defined by Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) criteria with symptoms of delusions or hallucinations, which have been present, at least intermittently for one month or longer

 Mini Mental State Examination (MMSE) score of 6 to 24 points

 Patients capable of self locomotion or locomotion with the aid of an assistive device

 Patients with an identified caregiver or proxy

 For Extension Phase:

 Eligible patients were males and females who had completed the 10-week Acute Phase in either treatment group; had a Week 10 Total Score of ≥ 6 on the NPI; and were, in the judgment of the investigator, deemed suitable for participation in the long-term trial.

 Treatment beyond 140 weeks:

 All subjects who completed the extension phase of CN138-006 in any French Investigational Site may be considered eligible for entry until they are no longer receiving clinical benefit, per the investigator's judgment

Exclusion criteria: :

 Patients with an Axis I (DSM IV) diagnosis of:

 delirium

 amnestic disorders

 bipolar disorder

 schizophrenia or schizoaffective disorder

 mood disorder with psychotic features

 Patients with reversible causes of dementia

 Patients with psychotic symptoms continuously present since prior to the onset of the symptoms of dementia

 Patients with psychotic symptoms that are better accounted for by another general medical condition or by direct physiological effects of a substance

 Patients with a current major depressive episode with psychotic symptoms of hallucinations or delusions

 Patients with a diagnosis of dementia related to infection with the human immunodeficiency virus

 Patients with substance-induced persistent dementia

 Patients with dementia due to vascular causes, multi-infarct, head trauma, Pick's disease, Parkinson's disease, frontal or temporal dementia, Lewy body dementia, or any specific non-Alzheimer's type dementia

 Patients with seizure disorders

 Patients who have been refractory to neuroleptics used to treat psychotic symptoms in the past when treated for an adequate period with a therapeutic dose, unless permission is obtained from Bristol-Myers Squibb

 Patients who have met DSM-IV criteria for any significant substance use disorder within the 6 months prior to the start of screening


Once-daily Therapy for Streptococcal Pharyngitis

Summary: In some studies once daily amoxicillin therapy might be treatment of choice for Group A β-hemolytic Streptococcus pharyngitis in comparison with three to four times daily treatment with oral penicillin V.
Inclusion criteria: inclusion criteria:

 inclusion criteria:

 Age of 6 to 15 years old.

 The criteria in clinical examination including objective signs (fever, Erythema or exudate of tonsils, enlarged lymph nodes) and subjective sign(sore throat). Neck tenderness, abdominal pain and pharynx petechia were also considered.

 No antibiotic was used during the week before.

 -Performing throat culture before the initiation of drug administration

 Positive throat culture indication GABHS

 No previous history of allergy to penicillin .

Exclusion criteria: :

 Age of below 6 years old or above 15 years old.

 No signs of pharyngitis in the clinical examination

 Antibiotic use during the week before.

 Throat culture was not performed before the initiation of drug administration.

 Negative throat culture or the culture indicates a microorganism other than GABHS.

 History of allergy to penicillin

 Not using drugs or not following the treatment in the field of having the second culture performed.

['Amoxicillin', 'Intramuscular Benzathin Penicillin G']

Amoxicillin
Intramuscular Benzathin Penicillin G


Finding Atrial Fibrillation in Patients With Unexplained Stroke Using Longterm Cardiac Monitoring

Summary: The SURPRISE study investigates atrial fibrillation(AFIB) in patients with a previous unexplained stroke. It uses long term monitoring of the heart of up to three years, searching for paroxysmal atrial fibrillation(PAF) otherwise undetected in this population.
Inclusion criteria: inclusion criteria:

 Computerized Tomography (CT) or Magnetic resonance imaging (MRI) verified cryptogenic stroke or TIA;

 > 18 years of age,

 the ability to provide a written consent

Exclusion criteria: :

 prior or known AFIB

 AF found during work up including 24 hour telemetric monitoring.


Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)

Summary: The KYOTO HEART Study is to assess the add-on effect of valsartan, an Angiotensin-Receptor Blocker, on top of the conventional treatment in high risk patients in Japan with hypertension in terms of the morbidity and mortality.
Inclusion criteria: inclusion criteria:

 Clinical diagnosis of hypertension

 Clinical diagnosis of one or more risk factors, such as diabetes, smoking habit, lipid metabolism abnormality, history of ischemic heart disease (IHD) or cerebrovascular disease, obesity (BMI>25), chronic heart failure (NYHA II-III), and electrocardiogram (ECG) abnormality (LVH)

Exclusion criteria: :

 Patients who have already been administered ARB

 Patients with IHD within 6 months after percutaneous coronary intervention(PCI), and who are stable but are going to implement PCI or coronary artery bypass grafting(CABG)

 Severe/malignant/secondary hypertensive patients

 Pregnant women and women of childbearing potential

 History of heart failure, unstable angina, myocardial infarction, PTCA, or CABG within the preceding 6 months

 Arrhythmia needed to be treated or accompanied with symptoms, second or third degree AV block

 Severe renal impairment (Serum creatinine >3.0 mg/dl)

 Severe hepatic impairment (Hepatic failure, Cirrhosis, etc.)

['Hypertension', 'Ischemic Heart Disease', 'Congestive Heart Failure', 'Stroke']

Hypertension
Ischemic Heart Disease
Congestive Heart Failure
Stroke


A Study to See if hENT1 Testing on Tumour Tissue Can Predict Response to Treatment With Gemcitabine Chemotherapy and if a Different Chemotherapy Called FOLFOX is Better Than Gemcitabine in Metastatic Pancreas Cancer

Summary: Chemotherapy is often used to help shrink the cancer temporarily and may improve survival for patients with incurable pancreas cancer that has spread to other organs. In Canada, the gemcitabine chemotherapy is used to treat pancreas cancer that has spread. The combination of oxaliplatin with other chemotherapies, including 5-fluorouracil, leucovorin, and irinotecan has also been studied and has benefit for patients with advanced pancreas cancer. To date, there is no test that can be done on a patient's tumour to tell if chemotherapy will work in pancreatic cancer. Human equilibrative nucleoside transporter 1 (hENT1) has been shown to be a possible predictor that gemcitabine may or may not work but this needs to be proven in a randomized study where patients get treated with gemcitabine or a different kind of chemotherapy while their tumours get tested for hENT1.~This study is being done because we want to prove that hENT1 can predict if gemcitabine will work in advanced pancreas cancer and if it can, we also would like to show that a different chemotherapy combination called FOLFOX (a combination of 5-fluorouracil, leucovorin, and oxaliplatin) will be helpful for patients whose tumours don't have hENT1.
Inclusion criteria: inclusion criteria:

 Histologically documented metastatic pancreatic adenocarcinoma not previously treated with palliative systemic therapy

 Metastatic disease based on the presence of clinically and/or radiologically documents Measurable disease base on RECIST.

 Adequate tissue (core biopsy) available for IHC testing of hENT1. This may be from primary tumour or metastatic site. Fine needle aspiration biopsies will not be allowed. Histological/cytological confirmation of tissue to ensure sufficient material is available for hENT1 analysis by the Cross Cancer Institute is required prior to starting a patient on study. Biopsies from metastatic sites must be obtained ≥ 3 months after any adjuvant chemotherapy (if applicable). If a patient has had previous surgical resection of their primary tumours, that tissue can be utilized. Tissue sufficient for preparing ≥ 10 unstained slides for central storage and testing is required.

 ECOG performance status of 0 - 1.

 Age ≥ 18 years.

 Life expectancy of at least 3 months based on discretion of treating oncologist.

 Adequate hematologic function defined by the following laboratory parameters:

 Hemoglobin ≥ 100

 Platelet count ≥ 100

 Absolute granulocyte count ≥ 1.5

 Adequate hepatic and renal function defined by the following laboratory parameters:

 AST and ALT ≤ 2.5 X upper limit of institutional normal (≤ 5 if liver metastases)

 bilirubin ≤ upper limit of institutional normal

 calculated creatinine clearance of ≥ 50 mL/min using the Cockcroft-Gault formula, if just below 50 mL/min based on this formula then GFR ≥ 50 mL/min as determined by 24 hr urine collection

 Patients who have received prior chemotherapy or radiation delivered as part of initial curative therapy (i.e. neoadjuvant or adjuvant chemotherapy administered alone and/or concurrently delivered with radiation and/or surgery) are permitted as long as that treatment was completed at least 6 months prior to study start date.

 Patients may have received prior palliative radiotherapy (unless radiation was curative therapy to pelvis or to ≥ 25% of bone marrow stores) if this radiation was ≥ 4 weeks before study entry and patients must have recovered from the toxic effects of this treatment

 Patients may have received prior surgery if this surgery was ≥ 4 weeks before study entry and patients must have recovered from the toxic effects of this treatment.

 Patients must have the ability to read, understand, and sign an informed consent and must be willing to comply with study treatment and follow-up.

Exclusion criteria: :

 Patients who have received prior palliative chemotherapy for their metastatic pancreatic adenocarcinoma.

 Radical pancreatic resections (e.g. Whipple procedure) are not allowed < 6 months prior to randomization. Exploratory laparotomy, palliative (e.g. bypass) surgery, or other procedures (e.g. stents) are not allowed < 14 days prior to randomization. In any of the above cases, patients must be adequately recovered and stable prior to randomization.

 Prior treatment with > 6 cycles of traditional alkylating agent-based chemotherapy, > 2 cycles of carboplatin-based chemotherapy, prior treatment with irinotecan or oxaliplatin chemotherapy, or concurrent treatment with other experimental drugs or anti-cancer therapy.

 Curative radiation treatment to the pelvis or radiation therapy to ≥ 25% of bone marrow stores.

 Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, short gut syndrome, or history of bowel obstruction due to peritoneal metastases.

 Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or non-melanoma skin cancer, unless at least 5 years have elapsed since last treatment and the patient is considered cured.

 Any serious medical condition within 6 months prior to study entry such as myocardial infarction, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, cerebrovascular diseases, uncontrolled hypertension, uncontrolled diabetes, uncontrolled psychiatric disorder, serious infection, active peptic ulcer disease, or other medical condition that may be aggravated by treatment.

 Known dihydropyrimidine dehydrogenase (DPD) deficiency.

 Pre-existing neuropathy ≥ grade 2 from any cause.

 Patients with unstable metastasis to the central nervous system are excluded. Patients who have treated brain metastasis and are off steroids, anticonvulsants, and have documented stability of lesions for at least 3 months may be eligible. A CT scan or MRI is NOT required to rule out brain metastases unless there is clinical suspicion of CNS involvement.

 Pregnant or lactating women; women of child bearing potential must have a negative serum pregnancy test within 7 days of trial registration. Women or men of child bearing potential must use effective contraception (defined by the treating physician) which must be documented in study CRFs.

 Any other reason the investigator considers the patient should not participate in the study.

['5FU, leucovorin, oxaliplatin', 'Gemcitabine']


The Effect of Administration of Small Doses of Thyroxine on Glucose and Lipid Metabolism, in Type 2 Diabetes Mellitus.

Summary: We investigated the effect of the administration of small doses of thyroxine to healthy humans and patients with type 2 diabetes on postprandial forearm muscle glucose uptake, insulin sensitivity indices, lipid metabolism, in vitro glucose uptake and GLUT4 recruitment in the plasma membrane of monocytes.
Inclusion criteria: inclusion criteria:

 Healthy or treatment naive type 2 diabetes euthyroid subjects, with a micronodular texture of the thyroid gland.

 Recreationally active

 With stable body weight and diet during the last two months.

Exclusion criteria: :

 Any systemic disease(besides glucose abnormalities)

 Any medication therapy

 Diabetic complications

['thyroxine', 'Placebo', 'A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)']

thyroxine
Placebo
A meal (730kcal
50%carbohydrate
of which 38% was starch
40% fat
and 10% protein)


Sonographic Assessment and Visualization of Ectopics in Emergency Medicine

Summary: Observational study of the use of ultrasound by emergency physicians in the evaluation of patients at risk of ectopic pregnancy.
Inclusion criteria: inclusion criteria:

 pregnant females in 1st trimester

 present to emergency department

 complaint of abdominal/pelvic pain or vaginal bleeding

Exclusion criteria: :

 previous ultrasound diagnostic of location of pregnancy


PRION-1: Quinacrine for Human Prion Disease

Summary: PRION-1 aims to assess the activity and safety of Quinacrine (Mepacrine hydrochloride) in human prion disease. It also aims to establish an appropriate framework for the clinical assessment of therapeutic options for human prion disease that can be refined or expanded in the future, as new agents become available.
Inclusion criteria: inclusion criteria:

 Aged 12 years or more, diagnosed with any type of human prion disease.

Exclusion criteria: :

 In a coma, or in a pre-terminal phase of disease such that prolongation of the current quality of life would not be supported

 Known sensitivity to quinacrine

 Been taking any other putative anti-prion therapy for less than 8 weeks


Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC

Summary: The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
Inclusion criteria: inclusion criteria:

 Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures

 Adults (according to each country regulations for age of majority)

 Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation

 Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment

 World Health Organization (WHO) performance status 0-2

 Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline (please refer to IB for guidance)

 ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #6

 Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential

 Male patients must be willing to use barrier contraception, i.e., condoms

Exclusion criteria: :

 Previous (within 6 months) or current treatment with AZD9291

 Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4

 Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance.

 Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration;

 Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD

 Any of the following cardiac criteria:

 Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula :

 Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)

 Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

 Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment

 History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291

['T790M+ Testing', 'Baseline Visit Blood & Urine Testing', 'Baseline ECG', 'Visual Slit-Lamp Testing', 'AZD9291 Dosing']

T790M+ Testing
Baseline Visit Blood & Urine Testing
Baseline ECG
Visual Slit-Lamp Testing
AZD9291 Dosing


Cediranib (AZD2171, RECENTIN™) in Metastatic or Recurrent Renal Cell Carcinoma

Summary: Cediranib is being tested to assess its effectiveness on the growth of kidney cancer tumours and also how well it is tolerated.
Inclusion criteria: inclusion criteria:

 Confirmation of metastatic or recurrent renal cell carcinoma

Exclusion criteria: :

 Certain types of previous anti-cancer therapy for Renal Cell Carcinoma

 Patients with type I insulin-dependent diabetes or poorly-controlled type II insulin-independent diabetes

 Patients with a history of poorly controlled high blood pressure


Comparison of Two Mesh/Fixation Concepts for Laparoscopic Ventral and Incisional Hernia Repair

Summary: This is a monocenter randomized controlled trial comparing two systems of mesh and fixation device for the laparoscopic ventral and incisional hernia repair with respect to pain. It has been designed as a superiority study to proof the concept of previously published mathematical model of front abdominal wall.
Inclusion criteria: inclusion criteria:

 Informed Consent Form (ICF) signed by the patient or his/her legal representative

 primary or secondary ventral hernia less than 20 cm in length and less than 11 cm in width requiring elective surgical repair

 recurrence after former abdominal hernia repair WITH MESH

 recurrence after suture abdominal hernia repair CAN be included

Exclusion criteria: :

 no written informed consent

 patient under 18 years old

 emergency surgery (incarcerated hernia)

 patients with expected life time shorter than one year for example due to generalised malignancy

 BMI exceeding 40.0kg/m²

 contaminated surgical fields

 patients on immunosuppression, steroid therapy, constant pain therapy

['Intraperitoneal onlay mesh (IPOM) repair with the use of Phisiomesh implant and Securestrap fixation device.', 'Intraperitoneal onlay mesh (IPOM) repair with the use of Ventralight ST implant with SorbaFix fixation device.', 'Ventralight ST implant', 'ETHICON PHYSIOMESH®']


APC-111 Once a Day (QD) for 7 Days vs. Penicillin Taken Four Times a Day (QID) for 10 Days in Patients With Strep Throat

Summary: The purpose of the this study is to evaluate the safety of efficacy of APC-111 775 mg MP tablet once daily dosing for 7 days for treating patients with strep throat. The evaluation will look to confirm if APC-111 eliminates the bacterial infection (Streptococcus pyogenes).
Inclusion criteria: inclusion criteria:

 Give informed consent, assent and patient authorization

 Age 12 and over

 A clinical diagnosis of acute pharyngitis or tonsillitis

 A positive rapid Strep test

 Can swallow the oral study dosage forms

 Females must have a negative urine pregnancy test and be using acceptable birth control if sexually active

Exclusion criteria: :

 Chronic or recurrent odynophagia

 Need for hospitalization or IV antimicrobial therapy

 Pharyngitis known or suspected due to a pathogen resistant to beta-lactam antimicrobials

 Known carrier of S. pyogenes

 Allergies to penicillin or other beta-lactam antibiotics

 Any serious illness or concomitant condition that the investigator judges will preclude inclusion to the study

 Seizure disorder

 Pregnant or nursing

 Expectation of additional systemic antibacterials would be required for another condition

 Current drug or alcohol abuse

 Any experimental drug or device within the last 30 days

 Prior systemic antibiotic therapy within the last 30 days

 Hospitalization within the last month which included antibacterial therapy

 The presence of clinically significant hematologic conditions, etc

 Probenecid treatment

['Amoxicillin Pulsatile Release Multiparticulate Tablet (drug)']


The Relationship Between Vitamin D, Fingernail Thickness and Bone Density

Summary: Vitamin D deficiency is common in the elderly and contributes to the increased incidence of falls, hip fracture and depression in this population. An unknown number of elderly have vitamin D resistance resulting in a functional vitamin D deficiency state. Because there are no simple procedures or blood tests that identify vitamin D resistance, its prevalence and contribution to disability in the elderly is unknown. Our inability to screen for this condition precludes our ability to initiate and monitor treatment.~Previous studies indicate that fingernail thickness correlates with vitamin D status and may therefore provide a simple cost effective procedure to not only identify patients with vitamin D deficiency but also, those with vitamin D resistance. This procedure may also provide a way to monitor an individual's response to treatment.~This study is designed to demonstrate the association between fingernail thickness and vitamin D status.
Inclusion criteria: inclusion criteria:

 females 25-75 years of age with no known bone disorders

Exclusion criteria: :

 history of vertebral fractures or nonvertebral fractures without trauma

 prescription medications for prevention of osteoporosis (including vitamin D other than multivitamin and estrogen)

 history of malignancy other than basal cell or squamous cell cancer of the skin

 use of steroids or anticonvulsants in the 6 months prior to enrollment


Long Term Follow-up of Bone Mineral Density in Hormone Treated Turner Syndrome

Summary: Turner Syndrome (TS) is associated with osteopenia and osteoporosis. Reduced bone mineral density (BMD) and increased risk of fractures are present in many younger and middle-aged women with TS. The objective is therefore to describe longitudinal changes in BMD in TS.~The study is an observational follow-up study. Examinations at baseline, after 5 and 10 years.~Bone mineral density is measured by dual energy x-ray absorptiometry (DEXA) and bone turnover by bone markers.~Main Outcome Measures: Bone mineral density (BMD; grams/ square centimetre) were measured at lumbar spine, hip and the non-dominant forearm.
Inclusion criteria: inclusion criteria:

 Turner syndrome verified by karyotyping

Exclusion criteria: :

 untreated hypothyroidism or hyperthyroidism

 present or past malignant diseases

 clinical liver disease

 treatment with drugs known to interfere with bone metabolism (e.g. glucocorticoids)


Comparison Between Two Methods of Throat Swabbing

Summary: Throat swabbing is an important instrument in the diagnosis of strep pharyngitis and sometimes the main argument for antibiotic treatment. There is no firm knowledge about an appropriate method of the swabbing for receiving maximal sensitivity. We hypothesize that accurate swabbing from the pus will increase the sensitivity of the swabbing as compared to free swabbing. In order to check this hypothesis we will compare two swabs from the same throat. One that will be taken by a physician specifically from the pass and the second will be taken by a nurse as she used to do it. An increase of 10% of positive results will be accepted as a significant advantage.
Inclusion criteria: inclusion criteria:

 patients with sore throat, classified 2-3 according to Cantor's criteria

Exclusion criteria: :

 patients on antibiotic treatment

 suspected carriers of streptococcus


Ultrasound in Undifferentiated Hypotension

Summary: Background~Symptomatic undifferentiated hypotension represents a negative prognostic factor and the strongest predictor of in-hospital mortality.~Misdiagnosis may lead to delayed or incorrect treatment of some life-threatening conditions.~Aim~- The aim of the study is to evaluate the feasibility and accuracy of a new bedside ultrasound method that consists in the focused imaging of the thorax, abdomen and leg veins, in emergency.~Methods~Hypotensive (<100 mm/Hg) patients presenting to our emergency department, complaining of at least one of the neurologic, respiratory and cutaneous signs and symptoms of inadequate tissue perfusion, are prospectively studied by ultrasound-focused assessment of the heart, lungs, inferior vena cava, peritoneum, aorta and leg deep veins.~On the basis of physical examination and ultrasound results, the operator declares the diagnostic hypothesis without influencing the attending physician and the following diagnostic procedure (which includes ultrasound, when needed).~The diagnostic hypothesis is compared with the final diagnosis, obtained after the hospital route and discussed by a panel of three blinded experts (one radiologist, one cardiologist and one emergency physician).~The statistical agreement is calculated by the k of Cohen with p-value, confidence intervals and raw agreement (Ra).
Inclusion criteria: inclusion criteria:

 Arterial pressure <100 mm/Hg at presentation

 At least one of the following symptoms:

 Unresponsive

 Syncope

 Impaired mental status

 Respiratory distress

 Severe malaise and fatigue

Exclusion criteria: :

 Patients undergoing cardiopulmonary resuscitation

 Trauma patients

 Electrocardiographic and clinical diagnosis of STEMI or NSTEMI

 Clear cause of shock that needs immediate intervention (hemorrhage, gastrointestinal bleeding, drugs overdose)

 Late evolution of shock state in a patient already treated with known diagnostic tests


A Study to Evaluate the Effects of Asoprisnil(J867) in Women With Uterine Fibroids Who Are Scheduled for a Hysterectomy

Summary: The objective of this study is to evaluate the effects of 10 mg and 25 mg doses of asoprisnil, compared to placebo, taken daily for 12 weeks, on uterine blood flow and the morphology of the endometrium and uterine fibroids.
Inclusion criteria: inclusion criteria:

 Premenopausal women, at least 18 years of age

 Diagnosis of uterine fibroid(s), confirmed by ultrasound

 History of menstrual cycles between 17 and 42 days

 Otherwise in good health

 Scheduled for a hysterectomy at the end of the treatment period

 Negative pregnancy test

 Agrees to double barrier method of contraception

 Pap test with no evidence of malignancy or pre-malignant changes

 Endometrial biopsy with no significant histological disorder

Exclusion criteria: :

 Less than 3 months after having a baby or breast-feeding

 Any abnormal lab or procedure result the study-doctor considers important

 Severe reaction(s) to or are currently using any hormone therapy

 History of cancer or alcohol or drug abuse

 Diagnosis of Polycystic Ovary Syndrome

 History of prolactinoma

 Current use of Intrauterine Device

 Significant gynecological disorder

 Uterine size > 32 weeks gestation

 Current diagnosis of endometriosis

 Uterine artery embolization within 6 months


Prevalence of Colon Cancer in Pyogenic Liver Abscess

Summary: Although a proportion of pyogenic liver abscess may originated from colonic mucosal lesions, the prevalence of colonic neoplasm in the patients with pyogenic liver abscess are still not evaluated yet. Thus, our group will find the prevalence of colonic neoplasm in the group of cryptogenic pyogenic liver abscess by colonoscopic examination.
Inclusion criteria: inclusion criteria:

 Pyogenic liver abscess radiologically and bacteriologically diagnosed

Exclusion criteria: :

 Amebic liver abscess

 Other causes of pyogenic liver abscess such as cholangitis, liver cancer, complication of transarterial chemoembolization or radiofrequency ablation to hepatocellular carcinoma

 Refusal to colonoscopic examination

 Inadequate general patient status to perform the colonoscopic examination

 Patient who has had the screening colonoscopic examination within 1 year and showed normal finding or had 1 or 2 colon polyp in adequate exam


Plasma Adiponectin Levels and Relations With Cytokines in Children With Acute Rheumatic Fever

Summary: We aimed to investigate if adiponectin facilitates diagnosis of ARF by analyzing adiponectin levels in acute and convalescent periods of the acute rheumatic fever and by comparing results with that of healthy control group; also by comparatively examining levels of adiponectin in ARF cases who had different clinical findings at presentation. In addition, we aimed to investigate its role in the pathogenesis of ARF by evaluating correlations with cytokines such as TNF-α, IL-6 and IL-8 and acute phase reactants.
Inclusion criteria: For the study subjects, diagnosis of ARF was made according to the Modified Jones criteria (4) and appropriate treatment was started. Patients were divided into three groups by clinical findings. Group 1 included patients with only chorea, while patients with arthritis and carditis were involved in Group 2 and patients with only carditis were included in the Group 3. A group with only arthritis was not established since the patients with isolated arthritis are usually followed up at primary and secondary healthcare facilities rather than referring those patients to our tertiary healthcare center.
Exclusion criteria:


Genetic Mechanisms of Chronic Obstructive Pulmonary Disease (COPD)

Summary: The purpose of this study is to determine whether genetic factors contribute to an individuals risk of developing obstructive lung disease from smoking cigarettes.
Inclusion criteria: Age greater than or equal to 40 years

 Cigarette smoking greater than or equal to 30 pack years

 Obstructive Spirometry

 First degree relative with smoking history willing to participate
Exclusion criteria:


Heliox-Driven Racemic Epinephrine in Treatment of Bronchiolitis in Pediatric ED Patients

Summary: The purpose of this study is to assess whether children with moderate to severe bronchiolitis treated with standard racemic epinephrine therapy via 70:30 helium-oxygen (heliox) driven nebulization will have improvements in measurements of airway more rapidly than those treated with conventional air-oxygen driven nebulization.
Inclusion criteria: inclusion criteria:

 Any child 2-12 months old seen in the emergency department.

 A clinical bronchiolitis score > 3 by modified Wood's Clinical Bronchiolitis Score (M-WCBS).

 Diagnostic criteria of bronchiolitis includes tachypnea, cough, prolonged expiratory phase, wheezing, rales, chest retractions, and hyperinflation of lungs on chest radiograph. After consenting a patient to the study, respiratory syncytial virus (RSV) infection will be tested by rapid enzyme-linked immunoabsorbent assay of nasal secretions.

Exclusion criteria: :

 No child will be excluded based on race or gender

 Patients under the age of 2 months or greater than 12 months

 Patients with cyanotic heart disease

 Patients with lobar pneumonia, defined by results of chest radiographs.

 The presence of interstitial disease or diffuse patchy marking consistent with atelectasis on chest radiographs will not exclude patients.

 Patients with croup.

 Patients with foreign body aspiration.

 Patients with history of cystic fibrosis, bronchopulmonary dysplasia or other chronic lung disease.

 Patients with liver or renal disease.

 Patients with sickle cell anemia.

 Patients requiring mechanical ventilation.

 Patients who develop supraventricular tachycardia secondary to racemic epinephrine administration.

 Patients with tracheomalacia or bronchomalacia.

 Patients who had received bronchodilators within 2 hours of initiation of the study.

 Patients who had received systemic corticosteroids within 72 hours of enrollment

 Patients who suffered from persistent airway hyperreactivity in the 3 months before the study.

 Patients who do not tolerate the nasal cannulae for 45 out of 60 minutes.


Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients

Summary: The purpose of this research study is to investigate whether or not oral maribavir is safe and effective compared to oral ganciclovir for preventing CMV disease when administered for up to 14 weeks in patients who have had a liver transplant.
Inclusion criteria: inclusion criteria:

 Orthotopic liver transplant recipient

 Donor CMV seropositive / Recipient CMV seronegative

 Enrolled within 10 days after liver transplant

 Able to swallow tablets

Exclusion criteria: :

 Multiple organ transplant

 HIV infection

 CMV disease

 Use of other anti-CMV therapy at time of enrollment


Experimental Study to Validate the Therapeutic Game CONEM-BETA

Summary: The purpose of the study is to assess the efficacy of the systematic application of the CONEM-BETA game in the subjective welfare of family caregivers of patients with Alzheimer's disease or other advanced stage dementia.
Inclusion criteria: inclusion criteria Family Caregivers:

 to be a family caregiver of an person diagnosed with possible or probable Alzheimer's disease or other advanced stage dementia

 show interest in participating

 Sign informed consent

 inclusion criteria Alzheimer's or dementia person:

 to have a probable or possible Alzheimer type dementia or other advanced dementia according to a diagnosis done by a Specialized Evaluation Unit

 GDS 5-6 and a minimental equal or lower than 12.

 to preserve a verbal comprehension of basic instructions

 to preserve the mobility of the arms, as well as the visual and auditive capacities that allow to conduct the activities.

Exclusion criteria:  Caregivers:

 to have a negative attitude towards the emotional interaction with his/her Alzheimer or dementia family member

 Unavailability

 to participate in other socio-educative interventions during the study period.

 Any other situation that makes the caregiver as not suitable according to investigator's criteria

['CONEM-BETA + socio-educational training', 'Socio-educational training only']

CONEM-BETA + socio-educational training
Socio-educational training only


Effect of Whole Body Vibration on Bone and Fall Related Parameters

Summary: The effect of whole body vibration (WBV) on bone strength and fall frequency in older adults is still vague. Although there is some evidence that WBV may impact Bone Mineral Density in very frail elderly, there is a lack of data concerning the effect of WBV in community-living elderly woman. We hypothesize that WBV significantly affects bone parameters as assessed by DXA, QCT, US and bone markers with parallel positive changes of fall related risk factors (power, strength, balance, and reaction time). We further hypothesize that the effects of WBV were superior to conventional resistance exercise.
Inclusion criteria: inclusion criteria:

 community living elderly females >/=65 years

 live expectation > 2 years

Exclusion criteria: :

 secondary osteoporosis

 CVD-events including stroke

 participation in other studies

 medication and illness affecting bone metabolism within the last 2 years

 medication with impact on falls

 low physical performance (<50 Watt during ergometry)

 excessive alcohol-intake

['whole body vibration', 'resistance exercise', 'wellness']

whole body vibration
resistance exercise
wellness


Study to Investigate Effects of Antiischemic Drug Therapy in Silent Ischemia

Summary: There is a lack of data on the prognostic importance of silent ischemia in totally asymptomatic subjects without history of coronary artery disease (CAD), and, particularly, on a possible benefit of medical therapy in such patients. SWISSI 1 therefore recruits totally asymptomatic subjects older than 40 years of age without any history of CAD but one cardiovascular risk factor with documented silent ischemia. Participants are randomized to open antianginal drug therapy and risk factor control versus only risk factor management and followed up for ≥ 10 years.
Inclusion criteria: inclusion criteria:

 Documented silent myocardial ischemia type I

 At least one cardiovascular risk factor

Exclusion criteria: :

 History of cardiovascular disease

['bisoprolol', 'amlodipine', 'molsidomine', 'acetylsalicylic acid']

bisoprolol
amlodipine
molsidomine
acetylsalicylic acid


Position of Children During Urine Collection: Evaluation Study

Summary: Urinary tract infection (UTI) is a frequently suspected cause of fever in young children, justifying urine cultures. Sampling procedures are decisive for the reliability of UTI diagnosis. Even though official guidelines recommend clean catch method, catheterization or suprapubic aspiration, urine bag collection remains widely used. In our experience, the rate of contaminated bag-obtained cultures reaches 30.2 %. In a recent study, the investigators have noticed that the rate of contaminated urine cultures was lower when children were kept in an upright position at the time of urine collection. The upright position could explain this decrease, perineum being less in contact with urine. These results are borderline significant, the investigators would like to confirm them with a specific study.
Inclusion criteria: inclusion criteria:

 Children aged 2 - 36 months

 Non-toilet-trained children

 Indication to bag urine collection with the following criteria :

 fever ≥ 38.5 °C

 unexplained fever

 and at least 1 of the following criteria for girls and uncircumcised boys, at least 2 criteria for circumcised boys :

 age ≤ 12 months

 fever ≥ 48 hours

 poorly tolerated fever (chills ± cyanosis ± pronounced weakness…)

 preceding episode of tract urine infection

Exclusion criteria: :

 Parents opposed to the participation of their children in the study

 Diarrhea

 Current antibiotic treatment or during the 8 preceding days of the urine collection

 Genitals / perineal anomaly


Acupuncture in the Treatment of Depression

Summary: The current large randomized placebo-controlled trial is testing the ability of acupuncture to treat major depression. The study is unique in that treatment effects will be from the perspective of both Western psychiatry and Chinese medicine.
Inclusion criteria: inclusion criteria:

 Must meet criteria for Major Depression.

 Must be free of other mental or physical disorders that could cause depression, and also free from conditions that would typically exclude participants from trials involving pharmacologic antidepressants.

 Cannot be receiving other treatments or require immediate clinical attention.
Exclusion criteria:


Treatment of Stable Both-Bone Midshaft Forearm Fractures in Children

Summary: We create a randomized clinical trial between the treatment with above elbow armcast alone and the treatment of above elbow in combination with a short arm cast for stable midshaft both-bone forearm fractures.
Inclusion criteria: inclusion criteria:

 both-bone forearm fracture

 age < 16 years

 dislocation

 stable

Exclusion criteria: :

 fracture older than 1 week

 no informed consent

 refracture

 open fracture (Gustillo 2 and 3)

['above or below elbow cast for the last 3 weeks of treatment']

['Fracture', 'Forearm', 'Midshaft', 'Child', 'Treatment']

Fracture Forearm Midshaft Child Treatment


A Prospective Randomized Study Evaluating the Recurrence Rate of Chronic Subdural Hematoma After Placing a Subperiosteal Drainage Compared to a Subdural Drainage

Summary: The aim of our study is to investigate in randomized controlled fashion whether the recurrence and complication rate, after insertion of subperiosteal drainage in the treatment of chronic subdural haematoma, is higher compared to insertion of subdural drainage.~We hypothesize that patients treated with a subperiosteal drainage do not show higher recurrence rates than those treated with a subdural drainage, and suffer less complications.
Inclusion criteria: inclusion criteria:

 Patient at least 18 years of age presenting with a symptomatic chronic subdural hematoma

 Chronic subdural hematoma verified on cranial CT or MRI

Exclusion criteria: :

 The surgeon decides based on intraoperative conditions to perform a craniotomy (e.g. acute hematoma indicating a craniotomy)

 Chronic subdural hematoma caused by another underlying illness (e.g. caused by over-drainage of a vp-shunt)

 no informed consent

['Subdural Drainage', 'Subperiosteal Drainage']

Subdural Drainage
Subperiosteal Drainage


Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment

Summary: This study aims to determine whether levodopa is effective in boosting learning and memory in healthy subjects and patients with dementia or Mild Cognitive Impairment.~We also examine in healthy subjects using functional magnetic resonance imaging which brain regions mediate improved learning after levodopa administration.
Inclusion criteria: inclusion criteria for patients with dementia:

 Patients: clinical diagnosis of AD or mild cognitive impairment

 primary language German

Exclusion criteria:  for healthy subjects and patients with dementia/MCI:

 Known allergy to levodopa or tetrazine

 History of medication/drug abuse

 Acute nicotine withdrawal or > 15 cigarettes per day

 > 6 cups/glasses of coffee, caffeine drinks or energy drinks per day

 > 50 grams of alcohol per day

 Severe hypertonia (systole >160 mm Hg)

 Severe arteriosclerosis

 Diabetes, asthma, or glaucoma

 Severe hearing disability

 no focal brain lesions

 Premorbid depression or psychosis

 Medication with dopamine agonists or antagonists

 Parkinsonian symptoms

['Healthy', "Alzheimer's Disease", 'Mild Cognitive Impairment']

Healthy
Alzheimer's Disease
Mild Cognitive Impairment


Renal Stent Placement for the Treatment of Renal Artery Stenosis in Patients With Resistant Hypertension

Summary: The purpose of this trial is to test how well the iCAST™ RX Stent works in patients diagnosed with atherosclerotic renal artery stenosis and whether or not increased blood flow by the stent will help to control blood pressure.
Inclusion criteria: General inclusion criteria:

 Age ≥ 18 at the time of informed consent.

 Subject or subject's legal representative have been informed of the nature of the trial, agrees to participate, and has signed an Institutional Review Board (IRB)/Ethics Committee (EC) approved Informed Consent Form (ICF).

 Subjects that have bilateral kidneys or a solitary functioning kidney with Renal Artery Stenosis in at least one kidney and an average Systolic Blood Pressure (SBP) ≥ 155mmHg.

 Subject has a history of maximum tolerable dose of ≥ 3 anti-hypertensive medications of different classes, one of which must be a diuretic (for at least two weeks prior to Medical Documentation Screening period).

 a. A documented history for a minimum of 3 months showing reasonable and aggressive efforts to manage hypertension prior to consent. This must include the use of a broad variety of medications that have been used and failed or not tolerated.

 Subject must have documented clinical evidence to support likelihood of angiographic findings > 80% whether it is DUS, CTa, MRa or other medical evidence.

 New York Heart Association (NYHA) class I, II, or III the time of trial enrollment.

 Note: When a subject has bilateral Renal Artery Stenosis both of which require stenting, it is recommended to treat both kidneys with an iCAST™ RX Stent System during the index procedure. In the event that a subject needs a renal stenting procedure staged for renal protection, it is important that the Investigator treats the second renal artery with an iCAST™ RX Stent System after 30 days of the index procedure. If subjects with bilateral stenosis have only one lesion that meets protocol inclusion criteria that lesion should be treated per protocol. The recommendation is to NOT treat the second non-qualifying lesion, however if the operator feels strongly it is indicated, then they should treat per standard of care after 30-days post index procedure in order to comply with
Exclusion criteria:  #10.

 Subjects with flash pulmonary edema are allowed into the trial should they meet all other Inclusion and

['Renal Artery Stenosis', 'Hypertension, Renovascular']

Renal Artery Stenosis
Hypertension
Renovascular


Study of CPAP as Intervention After Lung Resection

Summary: The aim of this study was to compare the oxygenation index (OI), dyspnea, and pain scale and evaluate the duration of thoracic drainage and pleural air leaks after lung resection in two groups of patients: chest physiotherapy (CP) patients and combined CP and Continuous Positive Airway Pressure (CPAP) patients.
Inclusion criteria: inclusion criteria:

 medical diagnosis of lung cancer and an indication for lung resection (lobectomy, bilobectomy and pneumonectomy) with posterolateral thoracotomy;

 aged between 40 and 75 years.

Exclusion criteria: :

 Patients who refused to participate in the survey;

 lung resection with incisions other than posterolateral;

 patients who had contraindications to the use of noninvasive ventilation.

['Lung Cancer', 'Pulmonary Complications']


Anti Xa Levels Under Two Different Regimens of Enoxaparin VTE Prophylaxis After Sleeve Gastrectomy for Morbid Obesity

Summary: Approximately two thirds of the adult population in developed countries is categorized as over-weight or obese (BMI>30). In spite of worldwide increasing awareness, obesity is a major health concern. In the presence of numerous diets, medical therapies, and robust research, bariatric surgery remains the most effective means of weight reduction in morbidly obese patients (BMI>40, or BMI>35 with co-morbidities). However, bariatric surgery harbors a relatively high risk for postoperative complications; of them, venous thromboembolic events (VTE) are not common, but potentially lethal. Taken together with the propensity of morbidly obese patients to develop VTE, perioperative thromboprophylaxis is mandatory.~To date, low molecular weight heparins (LMWH) are most commonly used for VTE prophylaxis in the aforementioned population. Due to the pharmacologic properties of LMWH and the characteristics of surgically treated obese patients, the optimal dose that is to be utilized for VTE prophylaxis in this population remains unclear. Assessment of anti-FXa levels in the patients' plasma can be used in order to monitor LMWH activity. Levels of 0.2-0.5 U/ml have been proposed by some authors for VTE prophylaxis.~Few studies have compared different dosing regimens of enoxaparin (between 30mg-60mg q/12h) for VTE prophylaxis in the population undergoing bariatric surgery; nevertheless, these were small non- randomized trials, containing numerous methodological weaknesses. Hence, the optimal regimen of enoxaparin to be used for the prevention of VTE in the discussed population remains unclear.~The aim of the present study is to evaluate plasma levels of anti-FXa activity, comparing two most commonly used enoxaparin prophylactic regimens (40mg vs 60mg q/24h) in a large and homogenous cohort of sleeve gastrectomy patients. Although universally used by bariatric surgeons, the pharmacologic efficacy of these regimens has not been evaluated in patients undergoing bariatric surgery.
Inclusion criteria: inclusion criteria:

 Adult patient undergoing laparoscopic sleeve gastrectomy.

 The patient undergoes the surgery in the surgical wing of the Tel-Aviv Sourasky Medical Center.

 The patient has received full information regarding the studies nature, has agreed to participate and has given informed consent (documented by a signed informed consent form).

Exclusion criteria: :

 Patients with a previous Venous Thromboembolic Event.

 Patients requiring an IVC filter.

 Patients with known thrombophilia due to coagulation factor disorders (i.e factor V leiden).

 Patients with a bleeding disorder

 Patients with renal failure.

['40mg Enoxaparin', '60mg Enoxaparin', 'Control']


Study to Evaluate the Effectiveness of FluMist Vaccination in a School-Based Intervention Program

Summary: To measure the effectiveness of influenza vaccination in school children by comparing, between target(i.e., children are offered FluMist) and control (i.e., children are not offered FluMist) school families.
Inclusion criteria: inclusion criteria:

 Healthy children enrolled in the target schools.

 Written informed consent obtained from the child's parent(s) if they agree to participate.

Exclusion criteria: :

 History of severe hypersensitivity (anaphylactic response) to egg products or previous FluMist

 FluMist is licensed exclusively for use in healthy individuals age 5-49 years. Therefore children for whom annual receipt of inactivated influenza vaccine for specific medical condition(s) is recommended will not be eligible. These conditions include:

 Asthma, other chronic pulmonary diseases, kidney disease, metabolic disease, heart disease, or hemoglobinopathy

 Immunosuppression of child

 Severe immunosuppression of a household member

 Pregnancy

 Past history of Guillian-Barre Syndrome

 Aspirin therapy within 1 month prior to FluMist or the anticipated use of aspirin containing products for one month after FluMist administration

 Administration of any inactivated vaccine within 2 weeks or any live vaccine within 4 weeks prior to receipt of FluMist

 Received anti-influenza medication in the past 48 hours

 Fever in the past 72 hours

 Moderate to severe nasal congestion (inability to breathe through the nose) or acute phase URI symptoms until the congestion has improved


Dynamic Splinting After Total Knee Arthroplasty

Summary: The purpose of this study is to evaluate the effectiveness of a dynamic splinting system for knee flexion contracture following a total knee arthroplasty.
Inclusion criteria: inclusion criteria:

 Reduced flexibility in AROM of knee extension

 Pain that is worsened by bending over while legs are straight

 Impaired gait pattern

 Ability to understand informed consent and experiment responsibilities

Exclusion criteria: :

 Fractures

 Knee sepsis

 Osteomyelitis or any orthopedic infection

 Extensor mechanism dysfunction

 Psoriasis

 Knee joint neuropathy

 Previous Stroke or Brain Injury


Cell Infusion Intraportal Autologous Bone Marrow Mononuclear as Enhancer of Liver Regeneration

Summary: This is a randomized controlled trial in which the safety and feasibility of cell therapy medicinal product shall be measured by comparing the variables of the response after treatment compared to baseline prior to implementation. Secondarily the results obtained are compared with each of the study groups.~Patients will receive concomitant basic pharmacological treatment for maintaining liver function.~All patients will be equally medically treated. The hypothetic test is to propose mononuclear cells from the bone marrow infused in the territory hepatic portal remaining segments (II and III) to be performed while contralateral portal embolization provides progenitor cells hepatic regenerative capacity that would shorten the time of liver regeneration and increase residual volume, facilitating the realization of an extended hepatectomy with greater assurance of maintaining proper residual function and adequate surgical margins.
Inclusion criteria: inclusion criteria:

 - Patients of both sexes aged ≥ 18 years.

 - Standard analytical parameters, defined by:

 Leukocytes ≥ 3000

 Neutrophils ≥ 1500

 Platelets ≥ 100,000

 Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 1.5 standard range institution

 creatinine ≤ 1.5 mg / dl

 - Patients with liver space occupying lesion (LOE) that require extended hepatic resection.

 Patient selection should be cautious, covering basically 5 types of liver damage which must be submitted prior to liver volumetry:

 Metastatic Disease subsidiary right hepatectomy extended to segment IV

 Metastatic Disease subsidiary right hepatectomy with suspected diseased liver (neoadjuvant chemotherapy) (in cases of doubt may be used liver function test indocyanine green)

 Bilobar liver metastases with multiple nodules in the right lobe and more than 3 nodules greater than 30 mm in the left hepatic lobe (LHI) will perform lumpectomies the LHI + right portal branch ligation (or postoperative percutaneous embolization) in order to make right hepatectomy 4-6 weeks (two stage surgery)

 Subsidiary Hepatocarcinoma extended right hepatectomy

 Liver Injury benign / malignant (Hemangiomas, hydatid cysts or liver tumors / primary bile hepatoblastoma), which by extension threatens the viability of the remaining liver tissue.

 4 - Patients give their written informed consent for participation in the study and provide sufficient guarantees adherence to protocol according to the opinion of the investigator in charge of the patient care.

Exclusion criteria: :

 Different tumor records current disease or any disease hematologic.

 Patients with uncontrolled hypertension.

 Severe heart failure (NYHA IV).

 Patients with malignant ventricular arrhythmias or unstable angina.

 Diagnosis of deep vein thrombosis in the previous 3 months.

 Adjunctive therapy including hyperbaric oxygen, vasoactive substances, agents or angiogenesis inhibitors against Cox-II.

 BMI> 40 kg/m2.

 Patients with alcoholic with active alcoholism.

 Proliferative retinopathy.

 Concomitant disease that reduces life expectancy to less than a year.

 Difficulty in monitoring.

 Heart failure or ejection fraction (EF) <30%.

 Stroke or myocardial infarction within the last 3 months.

 Pregnant women or women of childbearing age who do not have adequate contraception.

['Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments.']


Controlled Acute Hypoxia Study Comparing Pulse Oximetry to Arterial Blood Samples During Motion

Summary: To validate the proposed claims for pulse rate and saturation accuracy in a diverse subject population during motion over a specified saturation range.
Inclusion criteria: inclusion criteria:

 Male or female of any race

 18-50 years old, inclusive

 Females: negative urine pregnancy test on the day of study participation (prior to exposure to hypoxia)

 Completed within the last year: physical exam by a licensed physician, physician assistant (PA), or advanced practice nurse; including a 12 lead ECG, a medical history, and blood test (complete blood count and sickle cell trait/disease screening)

 Meets specific demographic requirements for the monitoring device under study

 Willing and able to provide written informed consent

 Able to participate for the duration of the evaluation

Exclusion criteria: :

 A room-air baseline % modulation < 1.5% on all four fingers on the test hand

 Under 18 years or over 50 years of age

 Pregnant and/or lactating women

 Hypertension: on three consecutive readings, systolic pressure greater than 145 mm Hg or diastolic pressure greater than 90 mm Hg

 Ventricular premature complexes (VPC's) that are symptomatic or occur at a rate of more than four per minute

 History of seizures (except childhood febrile seizures) or epilepsy

 History of unexplained syncope

 Daily or more frequent use of anxiolytic drugs (benzodiazepines) for treatment of anxiety disorder

 Recent history of frequent migraine headaches: average of two or more per month over the last year

 Compromised circulation, injury, or physical malformation of fingers, toes, hands, ears or forehead/skull or other sensor sites which would limit the ability to test sites needed for the study. (Note: Certain malformations may still allow subjects to participate if the condition is noted and would not affect the particular sites utilized.)

 History of acute altitude sickness at or below moderate elevation (up to 5,000-10,000 feet) defined as three or more of the following symptoms: moderate to severe headache, general malaise, dizziness/lightheadedness, nausea/vomiting, fatigue/weakness, shortness of breath, nosebleed, persistent rapid pulse, or peripheral edema

 History of significant respiratory disease such as severe asthma or emphysema or sleep apnea

 Sickle cell disease or trait

 Clinically significant abnormal finding on medical history, physical examination, clinical laboratory test or ECG. Clinical significance will be assessed by the principal investigator or study physician as designated.

 History of stroke, transient ischemic attack or carotid artery disease

 History of myocardial ischemia, angina, myocardial infarction, congestive heart failure or cardiomyopathy

 History of chronic renal impairment

 Severe contact allergies to standard adhesives, latex or other materials found in pulse oximetry sensors, ECG electrodes, respiration monitor electrodes or other medical sensors

 Unwillingness or inability to remove colored nail polish or artificial nails from test digit(s)

 Unwillingness or inability to give informed consent

 Prior or known allergies to: lidocaine (or similar pharmacological agents, e.g., Novocain) or heparin

 Recent arterial cannulation (i.e., less than 30 days prior to study date)

 Six or more arterial cannulations of each (right & left) radial artery

 History of clinically significant complications from previous arterial cannulation

 Current use of blood thinners: prescription or daily aspirin use

 History of bleeding disorders or personal history of prolonged bleeding from injury.


Impact of Pharmacotherapy Management in Patients With Alzheimer's Disease

Summary: In Brazil, patients with Alzheimer's disease (AD) receiving free drugs of government. Even having access to, little is known about the effectiveness, safety and adherence of drug therapy in this group of patients. The research aims to promote adherence and develop strategies to address Drug-Related Problems (DRP's) in AD patients elderly of reference centre for the Elderly of Araraquara. The clinical parameters will be assessed at the beginning and after the educational intervention period from April 2014 to April 2015.
Inclusion criteria: inclusion criteria:

 Elderly patients who are assisted in CRIA, diagnosed with Alzheimer's in use of rivastigmine or donepezil or galantamine, assisted by the Program for special drugs.

 Be resident in the city of Araraquara / SP

 Accept part of pharmacotherapeutic follow-up;

 Sign the Statement of Informed Consent Form (ICF).

Exclusion criteria: :

 Fold over pharmacotherapy follow-up;

 Being institutionalized;

 Patients unable to respond to collection instruments MMSE and CDR data;

 Patient without phone contact.


Effects of Mirtazapine on Appetite in Advanced Cancer Patients

Summary: Primary objective: This is a preliminary study to determine if Mirtazapine in comparison to placebo will improve appetite in advanced cancer patients with anorexia and weight loss. An improvement of appetite is defined as a decrease of 2 in the appetite score from baseline on the Edmonton Symptom Assessment Scale (ESAS) at day 15 (+/-3 days).~Secondary objective-A: To determine if Mirtazapine in comparison to placebo will improve insomnia ( as measured by Pittsburgh Sleep Quality Index) on day 15 ( +/- 3 days), and day 29 ( +/- 3 days)~Secondary objective - B: To determine if Mirtazapine in comparison to placebo will improve other common symptoms such as pain, nausea and fatigue( as measured by ESAS), depression and anxiety ( as measured by Hospital Anxiety and Depression scale), and quality of life ( as measured by Functional Assessment of Anorexia/Cachexia Therapy ) in advanced cancer patients with anorexia/cachexia, on days 15 (+/-3 days), and 29 (+/-3 days)~Other Objectives:~To provide exploratory data on the effects of Mirtazapine on weight gain, and preservation/gain lean muscle mass ( anthropometric measurements and Bioelectric Impedance), on days 15 (+/-3 days), and 29 (+/-3 days).~To provide exploratory data on the effects of a Mirtazapine dose increase to 30 mg on decreased side effects of drug and increased appetite on day 29 (+/-3 days).
Inclusion criteria: inclusion criteria:

 Advanced cancer patients seen in outpatient clinics or inpatient units at MD Anderson Cancer Center, with presence of anorexia for at least one month, and accompanied by weight loss of > 5 % of pre-illness body weight in the last 6 months. Anorexia on the day of enrollment (day 0 +/-3) must be > 4/10 on ESAS.

 Patients > 18 years of age

 Karnofsky Performance score of > 40 at time of inclusion into study

 Ability to provide informed consent and comply with study procedures

 Ability and willingness to return to engage in telephone follow-up by research nurse on days 2 (+/- 3 days), 8 (+/- 3 days), 16 ( +/- 3 days), and 22 (+/- 3 days) and return to outpatient clinic for evaluation on days 15 (+/- 3 days), and 29 (+/- 3 days).

 Negative urine pregnancy test at time of inclusion into study for female patients of childbearing potential, within 24 hours of study enrollment.

 For patients receiving chemotherapy eligibility to be determined after discussion with primary oncologist

 Drowsiness of </= 4/10 on ESAS at baseline due to known potential sedating effects of Mirtazapine

 Patient can continue all medications including complementary therapies or antineoplastic therapy while on-study (with the permission of their Attending MD) if they have been on stable dose for at least 2 weeks.

 Patients who are on stable doses of antidepressants for at least 2 months.

Exclusion criteria: :

 Patients who have known dementia or delirium at time of enrollment as determined by a physician.

 Known hypersensitivity to any ingredient of Mirtazapine

 Inability to maintain oral intake over the course of the study, such as with mechanical obstruction of the alimentary tract or intractable vomiting

 Ongoing use of tube feeding or parenteral nutrition

 Current use of corticosteroids (with the exception of scheduled doses during time of chemotherapy), dronabinol, testosterone and progesterone derivatives such as megestrol acetate, or in the preceding 1 week prior to study enrollment.

 Pregnancy or lactation or unwillingness to use contraceptives

 A score of 11 or more, in each subscale of the Hospital Anxiety and Depression scale (HADS) indicating clinical depression or anxiety. Those with HADS scores of > 11 at baseline indicating moderate or severe depression will be excluded from the study and will be referred for appropriate follow up by counselor and psychiatry evaluation.

 Patients on chronic use of benzodiazepines are excluded

['Advanced Cancer', 'Anorexia', 'Weight Loss', 'Insomnia']

Advanced Cancer
Anorexia
Weight Loss
Insomnia


Investigation of Tibolone and Escitalopram in Perimenopausal Depression

Summary: Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The importance of clearly identifying and treating a disorder that is increasingly referred to as perimenopausal depression is highlighted by the wide-reaching impact this can have on the lives of women suffering from it. This is not a minor or short term mood disturbance; it is a severe depressive illness, needing effective and early treatment. Relationships, employment, participation in social roles and individual well-being can all be disrupted by the combination of the mood, hormonal and physical changes associated with the transition to menopause. The term perimenopausal depression denotes the onset of depression coinciding with the onset of reproductive hormone changes.~Many women with this type of depression experience serious and long term debilitating symptoms. Treatment commonly draws on traditional approaches for the management of major depression including the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) as the first line response. However, standard treatment of perimenopausal depression using antidepressants has only shown small improvements at best and at worst, is associated with severe side effects. Some SSRIs have been shown to be less effective in postmenopausal women compared to child bearing age women. Hormone treatments directly targeting the fluctuating reproductive hormone systems (in particular estrogen) through the administration of compounds such as tibolone, have significant potential as a better overall treatment.~To date, there is still a lack of clear clinical evidence about the best approach for the biological treatment of women with perimenopausal depression. The project we now propose to conduct is a 12-week randomised controlled trial (RCT) of 2.5 mg/day tibolone compared to 10mg/day of escitalopram (an SSRI that has targeted serotonin action)compared to placebo to discover the best treatment approach for a hitherto understudied depression that affects a large proportion of women in their late forties and fifties.
Inclusion criteria: inclusion criteria:

 Females who are currently physically well and between 45 and 55 years of age

 Current DSM-IV diagnosis of depression disorder

 Able to give informed consent

 Perimenopausal as determined by symptom profile on the Stages of Reproductive Aging Workshop and gonadal hormonal profile

Exclusion criteria: :

 Known abnormalities in the hypothalamic-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event, breast pathology, undiagnosed vaginal bleeding or abnormal Pap smear results in the previous 2 years.

 Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; or the presence of illness causing immobilisation.

 Patients receiving treatment for depression including antidepressant medications, electroconvulsive therapy (ECT) / Transcranial Magnetic Stimulation (TMS), formal psychotherapy or counselling, within the past 6 months

 Patients experiencing severe melancholia, neurovegetative symptoms or current suicidality necessitating acute hospitalisation or intensive psychiatric treatment.

 Patients with psychotic symptoms or past history of severe mental illness including schizophrenia, and bipolar disorder.

 Use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including tibolone or use of phytoestrogen supplements as powder or tablet

 Pregnancy / Lactation

 Smoking cigarettes and other nicotine products.

 illicit drug use and more than 3 standard drinks per day


Phase II Study of Interleukin-21 (rIL-21) vs Dacarbazine (DTIC) in Patients With Metastatic or Recurrent Melanoma

Summary: The purpose of this study is to find out what effects an experimental drug, called interleukin 21 or rIL-21, will have on malignant melanoma and whether these effects look promising compared to dacarbazine. In addition, this study will look at the side effects of rIL-21, and some special blood tests will be done to check the level of rIL-21 in the blood. This study will also look at previously removed melanoma tissue to determine which patients might benefit most from this treatment.~This research is being done because currently there is no effective treatment for this type of cancer.
Inclusion criteria: inclusion criteria:

 Histologically documented cutaneous malignant melanoma which is recurrent or metastatic and is not curable by surgical or other means.

 Patients must have tumour tissue from their primary and/or metastatic tumour available to assess putative molecular markers of response (paraffin block or 12 unstained slides).

 Presence of clinically and/or radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows:

 Chest X-ray > 20 mm, CT scan (with slice thickness of < 5 mm) >10 mm (longest diameter), Physical exam (using calipers) > 10 mm, Lymph nodes by CT scan > 15 mm measured in short axis.

 All radiology studies must be performed within 21 days prior to randomization (Exception: Within 28 days if negative).

 Patients must have either maximum tumour lesion size of ≤ 50 mm OR if tumour lesion is > 50 mm, LDH must be ≤ 2.5 x ULN.

 Patients must have a life expectancy of at least 12 weeks.

 Age > 18 years.

 ECOG performance status of 0-1.

 Previous Therapy:

 Immunotherapy: Prior adjuvant immunotherapy for melanoma is permitted if completed ≥ 1 month prior to study entry. No immunotherapy for metastatic disease is permitted. rIL-21 or dacarbazine must be the first systemic therapy for metastatic disease.

 Chemotherapy: Patients must not have received any prior chemotherapy (including regional therapy). rIL-21 or dacarbazine must be the first systemic therapy for metastatic disease (except for RAF and MEK-Inhibitors).

 Surgery: Previous surgery is permissible. Patient must be > 4 weeks since any major surgery.

 Radiation Therapy: Previous radiation therapy is permitted with exception of radiation therapy for brain metastases. Patients must be > 4 weeks since the last treatment with radiation. Exceptions may be made, however, for low dose, non-myelosuppressive radiotherapy. Patients must have recovered from the toxic effects of radiation.

 Laboratory Requirements: (must be done within 7 days prior to randomization) Hematology: Absolute granulocytes (AGC) ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L Chemistry: Serum creatinine ≤ 1.5 x UNL, Bilirubin ≤ UNL AST and ALT ≤ 2.5 x UNL, LDH ≤ 2.5 x UNL.

 Female patients of child-bearing potential must have a negative serum or urine pregnancy test within 7 days of enrollment.

 Sexually active patients must agree to use a medically accepted form of contraception while receiving study therapy.

 Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided but a sample form is given in Appendix VII. A copy of the initial REB approval and approved consent form must be sent to the central office. The patient must sign the consent form prior to randomization. Please note that the consent form for this study must contain a statement which gives permission for qualified representatives of the NCIC CTG, BMS, ZymoGenetics, the company collaborator, and regulatory authorities to review patient records (see section 16 for further details) and a statement which gives permission for NCIC CTG to access and study tissue for biomarker assessments.

 Patients must be accessible for treatment and follow-up. Patients randomized on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 2 hour's driving distance) placed on patients being considered for this trial.

 In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient randomization.

Exclusion criteria: :

 Patients with known HIV, Hepatitis B or Hepatitis C infection.

 History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for > 5 years.

 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction, other interventional cardiac procedure within the past 12 months, autoimmune conditions requiring chronic immunosuppressive therapy, or psychiatric illness/social situations that would limit compliance with study requirements.

 Patients may not have received any other investigational agents within 28 days of study entry, and may not receive concurrent treatment with other anti-cancer therapy or investigational agents while on protocol therapy.

 Patients with known brain metastases or history of CNS metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. A head CT or MRI is required on all patients to rule out brain metastases.

 Pregnant or lactating women. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with rIL-21 or dacarbazine, breastfeeding should be discontinued if the mother is treated with protocol therapy.

 Prohibited Medications: Long Term (> 7 days) Systemic Corticosteroids (e.g. prednisone, dexamethasone, etc.) because these may counteract the stimulatory effects of rIL-21 on lymphocytes. (Note: Topical steroids are allowed).