A Controlled Study to Evaluate the Safety and Immunogenicity of StreptAnova™ in Healthy Adults

Summary: This is a single-centered trial of a group A streptococcal (GAS) vaccine, StreptAnova™. The study is designed to assess safety and immunogenicity of three doses (0, 1, 6 months) of one dosage (600 µg protein) in healthy adults 18 through 50 years of age.
Inclusion criteria: inclusion criteria:

 Male and female healthy adults ages 18 to 50 years inclusive;

 Good general health as determined by screening evaluation no greater than 42 days before the first immunization;

 For women of childbearing age, use of adequate birth control from enrollment until 180 days after the last injection;

 Written informed consent, after reading the consent form and having adequate opportunity to discuss the study with an investigator or a qualified designee.

Exclusion criteria: :

 Presence of any febrile illness or any known or suspected acute illness on the day of any first immunization;

 Any chronic illness, whether or not active treatment is required;

 Any immunodeficiency (congenital or acquired);

 Any history of cardiac pathology (acquired or severe/persistent congenital);

 Any history of congenital malformation syndromes associated with congenital heart disease (syndrome complexes, e.g. VATER association; chromosomal disorders, e.g. Down's Syndrome; teratogenic agents, e.g. fetal alcohol syndrome; others, e.g. Noonan's);

 Any history of clinical manifestations of auto-immune or systemic diseases (inflammatory disorders, e.g. JRA, SLE, Kawasaki disease; inborn errors of metabolism, e.g. Fabry; connective tissue disorders, e.g. Marfan syndrome; neuromuscular disorders, e.g. Friedreich ataxia; endocrine-metabolic disorders, e.g. hypothyroidism; hematologic disorders, e.g. sickle cell anemia);

 Any history of acute rheumatic fever (ARF), post-streptococcal glomerulonephritis (PSGN), undiagnosed acute self-limiting polyarthritis (swelling, heat, redness or tenderness or pain and limitation of motion in >2 joints), or chorea (purposeless, involuntary rapid movements of the trunk and/or extremities);

 Any previous echocardiogram suggestive of cardiac pathology;

 Any immediate family history (parents, siblings) of ARF, PSGN, self-limiting polyarthritis, chorea, or a collagen-vascular disease such as Lupus or Sjögren's syndrome;

 Receipt of systemic glucocorticoids (a dose ≥ 20 mg/day prednisone or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within six months;

 Receipt of any investigational drug within six months, or prior participation in a clinical trial of a group A streptococcal vaccine;

 Receipt of blood products or immunoglobulin (IVIg or IMIg) within three (3) months of study entry/baseline serologic evaluation;

 Any physical findings suggestive of acute or chronic illness;

 History of receiving Adriamycin or other chemotherapy;

 Use of any of the following diet pills: fenfluramine, phentermine, or dexfenfluramins (also known as Pondimin, Redux, Adipex, or Fastin);

 History of sensitivity to any component of study vaccines;

 Evidence of tissue cross-reactive antibodies to human heart, joint cartilage, kidney, cerebral cortex or basal ganglia by indirect fluorescent antibody assay at pre-vaccination screening;

 Repeatable clinical laboratory abnormalities (blood or urine), as defined by lab normal ranges. To exclude transient abnormalities, the investigator may repeat a test up to twice, and if the repeat test is normal, subject may be enrolled;

 Echocardiographic finding of valvular dysfunction (stenosis, leaflet thickening or nodules, restricted leaflet mobility, or prolapse), LV dysfunction, atrial or ventricular enlargement, mild or greater mitral regurgitation or aortic insufficiency, moderate or greater tricuspid regurgitation or pulmonic insufficiency, pericardial effusion, or other cardiac pathology as identified by echocardiologist*;

 Receipt of any vaccines within 2 weeks of Dose 1;

 Clinically significant abnormality on screening electrocardiogram*

 Pregnancy or breastfeeding.

['StreptAnova™ (Group A streptococcal (GAS) vaccine)', 'Hepatitis B vaccine', 'Hepatitis A vaccine', 'Human Papillomavirus vaccine']


Examination of Brain Serotonin Receptors in Patients With Mood Disorders

Summary: The purpose of this study is to evaluate the function of certain brain chemicals and receptors in patients with mood disorders. This study will also examine how the stress hormone cortisol affects brain function.~Data suggest that serotonin 1A (5-HT1A) receptor function is abnormal in patients with mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BP). However, these data are limited because they are based on small sample sizes. In this study, PET scans will be used to compare 5-HT1A receptor binding potential between mood disorder patients and healthy volunteers.~All participants will have an initial medical and psychiatric evaluation. Depression severity, anxiety, negative thinking, level of functioning, intelligence, and cognitive functions will be measured. Urine, saliva, and blood will be collected. Women will have a pregnancy test and tests to determine menstrual phase and time of ovulation. Participants will undergo magnetic resonance imaging (MRI) and PET scans of the brain. Some participants will have other procedures such as a lumbar puncture. Participants with Cushing's disease will undergo imaging as a comparison group.
Inclusion criteria: inclusion criteria:

 MDD SAMPLES:

 Seventy subjects (ages 18 to 60) with MDD will be selected who additionally meet criteria for one of 3 subgroups:

 A) MDD, Currently depressed with FPDD, as defined by DSM-IV criteria for recurrent MDD, currently in a major depressive episode, who have a first degree relative with MDD but no first degree relatives with mania, alcoholism, or antisocial personality disorder.

 B) MDD, Currently in remission with a history of FPDD, defined as a period of at least six months with no more than one clinically significant symptom, and during which time subjects were not taking an AD agent. Subjects will thus meet the historical criteria for recurrent MDD (DSM-IV). We will also require that subjects previously had a least one antidepressant drug trial, to ensure that the severity of previous episodes warranted treatment.

 C) MDD, Currently depressed, non-FPDD. To assess the specificity of the findings in MDD to FPDD, a sample meeting criteria for MDD, currently in a depressive episode, but not FPDD will also be imaged.

 BIPOLAR DEPRESSED SAMPLE:

 Forty five subjects (ages 18 to 60) who meet DSM-IV criteria for bipolar disorder and are currently in a major depressive episode. Subjects may be inpatients or outpatients. Because effective treatment will not be discontinued for the purposes of this protocol, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry.

 HEALTHY, LOW RISK, CONTROL SAMPLE:

 One hundred and four subjects (ages 18 to 60) who have not met criteria for any major psychiatric disorder. The control subjects will have no known first or second degree relatives with mood disorders.

 CUSHINGS DISEASE CONTROL SAMPLE:

 Ten subjects (ages 18 to 60) with probable Cushing's Disease will be recruited who have both clinical and biochemical evidence of hypercortisolism (including urinary free cortisol excretion higher than the upper limit of normal (greater than 248) nmole/day, and marked central adiposity, cutaneous atrophy, proximal myopathy, and large purple striae). The diagnosis of probable Cushing's Disease will also have been established prior to referral via CRH and ACTH.

 MENSTRUALLY-RELATED DYSPHORIC DISORDER SAMPLE:

 (n equals 12; ages 18-50). These females are recruited, screened and diagnosed by collaboration under protocol number 81-M-0126, previously approved by IRB, entitled 'The Phenomenology and Biophysiology of Menstrually Regulated Mood and Behavioral Disorders', principal investigator, David Rubinow, M.D. As described in that protocol these subjects must have a regular menstrual cycle lasting 21 - 33 days and meet the following criteria: 1) history within the last two years of at least six months with menstrually-related mood or behavioral disturbances of at least moderate severity - that is, disturbances that are distinct in appearance and associated with a notable degree of subjective distress; 2) a 30 percent increase in mean negative mood ratings (relative to the range of the scale employed) in the premenstrual week compared with the week following the end of menses in at least two of the three cycles; 3) age 18 to 50; 4) not pregnant and in good medical health; 5) regular menses.

 REMITTED MDD WITH AND WITHOUT A HISTORY OF PPD:

 (n=40; ages 18-40). These subjects are recruited, screened and diagnosed by collaboration under 95-M-0097, previously approved by IRB entitled An Endocrine Modal for Postpartum Mood Disorders. These subjects will have a history of DSM-IV MDD. Twenty will also have had a hypomanic/manic episode that occurred within three months of childbirth and twenty will have not had the latter within three months of childbirth. Women will have been well for a minimum of one year, have a regular menstrual cycle for at least three months, medication free (including birth control pill), have no history of puerperal suicide attempts or psychotic episodes requiring hospitalization. Any women with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.

 HEALTHY FEMALE CONTROLS UNDER 95-M-0097:

 (n=20, age 18-40). These healthy control women are under an identical drug administration regimen as the 40 remitted MDD women above and will similarly be recruited and screened under 95-M-0097. They will meet the same criteria specified for the remitted MDD group above but will not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders. This healthy sample of females will have given birth.

Exclusion criteria: :

 Subjects must not have taken antidepressant or other medications likely to alter monoamine neurochemistry or cerebrovascular function for at least 3 weeks (8 weeks for fluoxetine) prior to scanning. Subjects being scanned at two points or the same point twice in their menstrual cycle must not have taken birth control pills for at least 6 months prior to scanning. However, effective medications will not be discontinued for the purposes of this study. Instead, subjects will be recruited who are not currently receiving psychotropic drugs. Subjects will also be excluded if they have:

 serious suicidal ideation or behavior;

 psychosis to the extent that the ability to provide informed consent is in doubt;

 medical or neurological illnesses likely to affect physiology or anatomy;

 a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria);

 current pregnancy

 current breast feeding;

 general MRI

['Mood Disorder', 'Bipolar Disorder', 'Depression']

Mood Disorder
Bipolar Disorder
Depression


ARIXTRA Local Study For Registration In China.

Summary: This is a local registration study in China to compare the safety and efficacy of ARIXTRA to Enoxaparine in patients undergoing elective major hip or knee replacement or a revision of components.
Inclusion criteria: inclusion criteria:

 Patients undergoing either an elective major hip or knee replacement or revision.

 Signed written informed consent. Men or women of non-child bearing potential(i.e., post menopausal or with hysterectomy of bilateral tubule ligation) or women of childbearing potential without any plan to have a child.

Exclusion criteria: :

 History of serious active bleeding in last 3 month

 Concurrent or history of thrombocytopenia ( Platelet< 100x109/L)

 History of hypersensitivity reaction to heparin, Low molecular weight heparin or pork product

 Acute bacterial endocarditis

 Congenital or acquired bleeding disease in last 3 months

 Concurrent uncontrolled ulcer or gastrointestinal disease with blood vessel dysplasia

 Concurrent hemorrhagic cerebrovascular disease or surgical history in cerebral, spine or eye

 Conditions need to leave a tubule in intradural or extradural

 Contraindication to anticoagulant or condition required to take long term oral anticoagulant

 Abnormality in hepatic (>1.5x UNL), renal (Clcr < 30ml/min) or cardiac function, uncontrolled hypertension or tumor Concurrent disorder of blood vessel in lower limb

 Positive result in Human Chorionic Gonadotropin test Participated in any other investigational study on Deep Vein Thrombosis prevention in last 90 days.

 Concurrently to have hip and knee or double hip/knee replacement at the same time

['ARIXTRA infusion', 'Enoxaparine infusion']

['Thromboembolism', 'Knee Replacement', 'Hip Replacement']

Thromboembolism
Knee Replacement
Hip Replacement


Antiplatelet Strategy for Peripheral Arterial Interventions for Revascularization of Lower Extremities

Summary: The purpose of this study is to evaluate whether clopidogrel 75 mg daily on a background of aspirin 75-100 mg/d for clinically indicated duration or for an additional 12 months will lead to an increased rate of primary patency, limb salvage, non-fatal myocardial infarction (MI), ischemic stroke, and survival, in patients receiving endovascular treatment of PAD at end of study treatment.
Inclusion criteria: inclusion criteria:

 General:

 Signed informed consent

 At least 18 years old

 Documented symptomatic iliac, femoropopliteal (FP) or below-the knee artery (BTK) atherosclerotic disease (Rutherford/Becker category 2, 3 or ≥4)

 Undergone clinically indicated uncomplicated endovascular intervention to one or more locations of the iliac, femoropopliteal below-the knee arteries

 Estimated survival ≥1 year in the judgment of the primary operator

 Pre-index procedure use of ASA, clopidogrel or both at any dose

 Angiographic:

 De novo or restenotic lesions in the common and/or external iliac artery, superficial femoral artery (SFA), popliteal artery, tibio-peroneal (TP) trunk, anterior tibial (AT) artery, peroneal artery (PA) or posterior tibial (PT) artery (applies to all target lesions if multiple)

 Subjects with multiple planned procedures can be enrolled after the completion of the last planned procedure.

Exclusion criteria: :

 General:

 Complicated qualifying procedure (perforation, flow limiting dissection, distal embolization requiring re-intervention, need for repeat endovascular, surgical revascularization, amputation or blood transfusion prior to hospital discharge following an index procedure

 Extended hospital stay >7 days following the index procedure

 Allergy to aspirin or clopidogrel

 Life expectancy less than 12 months due to other medical co-morbid condition(s) that could limit the subject's ability to participate in the trial, limit the subject's compliance with the follow-up requirements, or impact the scientific integrity of the trial

 Known hypersensitivity or contraindication to contrast dye that, in the opinion of the investigator, cannot be adequately pre-medicated.

 Intolerance to antiplatelet, anticoagulant, or thrombolytic medications

 Platelet count <90,000 mm3 or >600,000 mm3

 Serum creatinine >2.5 mg/dL

 Dialysis-dependent end stage renal disease

 Pregnancy

 Current participation in another drug or device trial that requires interruption of dual-antiplatelet therapy with aspirin or clopidogrel for the duration of the study

 Planned surgeries, endovascular or other non-vascular or cardiac procedures

 Concurrent warfarin or other chronic oral anticoagulant therapy

 Contraindication(s) to the use of AT (history of intra-cerebral bleed, presence of intra-cerebral mass, recent or <6 weeks gastrointestinal bleed, blood transfusion within the last 6 weeks, any trauma requiring surgery or blood transfusion within the last 4 weeks or any surgical procedure within the last 4 weeks.

 Angiographic:

 Endovascular intervention to iliac, femoropopliteal or BTK artery bypass graft

 Persistent, intraluminal thrombus of the proposed target lesion at the completion of the index procedure

 Perforated vessel as evidenced by extravasation of contrast media

 Vascular graft, aneurysm or postsurgical stenosis of the target vessel

['Clopidogrel', 'Acetylsalicylic acid (ASA)']


Mobile Stroke-Unit for Reduction of the Response Time in Ischemic Stroke

Summary: Stroke, the most common cause of permanent disability, the second most common cause of dementia and third most common cause of death, has tremendous socio-economic consequences.~Currently, systemic thrombolysis with the tissue plasminogen activator represents the only causal and approved treatment for acute ischemic stroke. However, the chances to save the brain tissue by a thrombolytic therapy exponentially decrease with proceeding time after onset of symptoms.~In most cases, the beginning of the thrombolysis therapy is delayed by a variety of factors, like delivery to the hospital, re-examinations and delay of blood analysis or of CT scans. Due to this, a thrombolytic therapy is possible only in a minority of the stroke patients (2-5 %). The aim of this study is to investigate whether a Mobile Stroke Unit, a rescue car with an integrated CT scanner, necessary for essential diagnostics, contributes to a better stroke management by saving precious time until a therapeutic decision is made. The trial is planned as a monocentric, randomised prospective trial.
Inclusion criteria: inclusion criteria:

 Age between 18 and 80 years

 Onset of symptoms until call at least 30 min prior to the end of the approved time window for thrombolysis (and not after awakening)

 Clinical signs of ischemic stroke with suddenly occurring, measurable neurological deficits defined as impairment of language, motor function, facial palsy or asymmetry

 Patient is willing to participate voluntarily and to sign a written informed consent. Informed consent will be obtained from each patient or the subject's legally authorized representative or relative.

 Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make undoubtfully clear that they are willing to participate voluntarily and must be able to understand an explanation of the contents of the information sheet.

Exclusion criteria: :

 Age younger than 18 or older than 80 years

 Non-acute onset of symptoms

 No focal stroke-like symptoms

 Pregnant patients


Haemodynamic and Cardiovascular Effects of Carbetocin and Oxytocin

Summary: A double-blinded randomised control trial conducted in the Department of Obstetrics and Gynaecology of a tertiary hospital, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for two years duration from January 1st, 2012 till December 31st, 2013.~The aim of the study is to compare the haemodynamic and cardiovascular effects between intravenous carbetocin 100 μg and intravenous oxytocin 5 IU in women undergoing elective Lower Segment Caesarean Section (EL LSCS).~Study hypothesis: A single injection of carbetocin is haemodynamically and cardiovascularly safe and has similar efficacy in comparison to a single injection of oxytocin.
Inclusion criteria: inclusion criteria:

 Viable, singleton pregnancy ≥ 37 weeks gestation undergoing EL LSCS.

 Low risk for post-partum hemorrhage, such as no proven abruptio placentae, placenta previa, multiple pregnancy, pre-eclampsia / gestational hypertension, previous PPH, obesity (based on BMI pre pregnancy which is ≥ 30 kg/m2), big baby.

 Ability to provide informed consent.

Exclusion criteria: :

 Emergency caesarean section

 Preterm Labour

 Grandmultipara

 Multiple Pregnancy

 Placenta Previa

 Previous PPH

 Maternal Obesity ( BMI pre pregnancy ≥ 30 kg/m2))

 Have co-morbidity illness such as hypertension/pre-eclampsia, established cardiac diseases, history or evidence of liver, renal, vascular, or endocrine disease and bleeding disorder.

 Contraindication to carbetocin and oxytocin

 Language Barrier

 Women undergoing general anaesthesia

 Women who has abnormal baseline ECG that suggestive myocardial ischemia


Omega-3 Fatty Acids and Muscle Protein Synthesis

Summary: The purpose of this study is to determine whether omega-3 fatty acid supplementation influences muscle protein synthesis rates in young and older adults.
Inclusion criteria: inclusion criteria:

 Body mass index (BMI) < 30 kg/m2;

 Age 18-45 yr; or

 Age 65-85 yr

Exclusion criteria: :

 Those taking medications known to affect substrate metabolism or medications that may confound the findings from our study (synthetic steroids, glucocorticoids etc.);

 Those with evidence of significant organ system dysfunction (e.g. diabetes mellitis, cirrhosis, hypo- or hyperthyroidism; hypertension);

 Body mass index > 30 kg/m2

 Age <18 yr, 45-65 yr or > 85 yr

 Those performing >1.5h of exercise/wk


Secretin (ChiRhoStim) Pancreas Perfusion for Pancreatic Adenocarcinoma

Summary: The purpose of this study is to test if secretin-enhanced CT is a useful noninvasive screening tool for pancreatic cancer in a high-risk population.
Inclusion criteria: inclusion criteria:

 Persons 50 years or older with recently diagnosed diabetes (within 2 years), with at least one of the following: no family history of diabetes, abdominal discomfort, anorexia, weight loss, elevated serum CA 19-9, or those undergoing EUS with or without Fine Needle Aspiration (FNA) for pancreatic cancer screening ; OR

 Persons 35 years old or older with familial pancreatic cancer with 2 or more first degree relatives with pancreatic cancer; OR

 Persons 35 years old or older with Peutz-Jeghers syndrome; OR

 Persons 35 years old or older with suspicious clinical symptoms of pancreatic cancer, but had normal CT of the abdomen with iodinated contrast within 2 weeks.

Exclusion criteria: :

 Persons with contraindication to iodinated contrast

 Allergy to iodinated contrast

 Renal insufficiency (serum creatinine > 1.5 mg/dl)

 Patients with contraindication to ionizing radiation

 Pregnancy

 Patients with previous pancreatic surgery

 Contraindication to secretin

 Allergy to secretin

 Acute pancreatitis


COmbined N-acetylcysteine and Bicarbonate in PCI To Reduce Adverse Side Effect of contrasT

Summary: This is a randomised controlled trial to investigate the efficacy of preventive regimen of hydration with high dose oral N-acetylcysteine and intravenous sodium bicarbonate pretreatment in patients with stable advanced renal insufficiency (CKD stage 3 and 4:GFR 15-60ml/min/1.73m2 calculated by Modification of Diet in Renal Disease Study equation (MDRD formula)) undergoing elective percutaneous coronary intervention (PCI).
Inclusion criteria: inclusion criteria:

 Age > 21 year

 Glomerular Filtration Rate (GFR) 15-60ml/min calculated by MDRD formula

 Scheduled to undergo elective PCI

 Able to receive 12 hours of pre-hydration

 Written informed consent

Exclusion criteria: :

 GFR less than 15ml/min or patients diagnosed with end stage renal failure

 Increase in serum creatinine levels of > 0.5mg/dl or 44umol/l in the previous 24 hours

 Preexisting dialysis

 Pulmonary edema or moderate to severe congestive heart failure (New York Heart

 Association [NYHA] III-IV)

 Patient unable to withstand the fluid load and hemodynamics compromise

 Uncontrolled hypertension (untreated systolic blood pressure > 160 mmHg, or diastolic blood pressure > 100mmHg.)

 Emergency cardiac catheterization (i.e. patient presenting with ST segment elevation myocardial infarction undergoing primary angioplasty)

 Recent exposure to radiographic contrast (within two days of the study).

 Allergic to radio-contrast

 Administration of sodium bicarbonate solution or NAC within 48 hours before the PCI.

 Patient unable to give consent

 Clinically vulnerable condition requiring continuous fluid therapy e.g. severe sepsis

 Use of NSAID, aminoglycocide, cyclosporin, cysplatin within 48 hours prior to PCI and throughout the study duration


Is a Low Thyreotropin Level Predictive of Recurrent Arrhythmia After Catheter Ablative Surgery?

Summary: Overt hyperthyroidism (so-called goiter in lay language) is a hormonal disturbance that is known to increase the risk of atrial fibrillation (a common heart arrhythmia with potentially severe consequences) in some patients. Previous research has indicated that even slight elevations in thyroid hormone levels - so called subclinical hyperthyroidism - may increase this risk. When atrial fibrillation and overt hyperthyroidism are found simultaneously in a patient, the hormonal imbalance must be treated first in order to later resolve the arrhythmia. It is unclear whether this strategy holds true for subclinical hyperthyroidism. Our two hypotheses are: 1) Subclinical hyperthyroidism is more prevalent in patients admitted for atrial fibrillation ablation than in the population as a whole, and 2) Patients with subclinical hyperthyroidism and atrial fibrillation benefit less from ablation than others.~As a control group, we have chosen patients admitted for ablation of AV-nodal Reentry Tachycardia at the same clinics as the cases. No correlation has ever been shown between AV-nodal Reentry Tachycardia and hyperthyroidism.
Inclusion criteria: inclusion criteria:

 Atrial fibrillation or AV-nodal reentry tachycardia

 Fulfills criteria for ablation (severe arrhythmia symptoms; for atrial fibrillation patients, having tried at least one antiarrhythmic agent with poor effect)

 Admitted for ablation for the first time

 Has left blood samples for thyroid status (TSH, free T4, free T3)

Exclusion criteria: :

 Atrial flutter

 Overt hyperthyroidism

['Atrial Fibrillation', 'Subclinical Hyperthyroidism']

Atrial Fibrillation
Subclinical Hyperthyroidism

:

 Atrial flutter

 Overt hyperthyroidism


Evaluation of the Efficacy and Safety of QVA149 (110/50 μg o.d.) vs Tiotropium (18 µg o.d.) + Salmeterol/Fluticasone Propionate FDC (50/500 µg b.i.d.) in Patients With Moderate to Severe COPD

Summary: This study will evaluate the efficacy and safety of QVA149 (110/50 μg o.d.) vs tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) in patients with moderate to severe COPD
Inclusion criteria: inclusion criteria:

 Patients who have signed Informed Consent Form prior to initiation of any study-related procedure.

 Male and female adults aged ≥ 40 years.

 Patients with moderate to severe airflow obstruction with stable COPD (Stage 2 or Stage 3) according to the 2014 GOLD Guidelines.

 Patients with a post-bronchodilator FEV1 ≥40 and < 80% of the predicted normal value, and post-bronchodilator FEV1/FVC < 0.70 at run-in Visit 101. (Post refers to 15 min after inhalation of 400 µg of salbutamol).

 Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack /day x 10 years, or ½ pack/day x 20 years). An ex-smoker is defined as a patient who has not smoked for ≥ 6 months at screening.

 Patients who are on triple treatment at least for the last 6 months (LAMA +LABA/ICS).

Exclusion criteria: :

 Patients who have not achieved acceptable spirometry results at Visit 101 in accordance with ATS (American Thoracic Society)/ERS (European Respiratory Society) criteria for acceptability (one retest may be performed for patients that don't meet the acceptability criteria) .

 Patients who have had more than one COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the last year prior to Visit 1.

 Patients who developed a COPD exacerbation of any severity either 6 weeks before the screening (Visit 1) or between screening (Visit 1) and treatment (Visit 201) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.

 Other protocol-defined inclusion/

['Chronic Obstructive Pulmonary Disease (COPD)']


Safety and Efficacy Study of Lithium for the Treatment of Pediatric Mania.

Summary: Study Design This is the second study of a multiphase, multicenter trial that will comprehensively examine lithium in the treatment of pediatric participants with bipolar I disorder. In order to examine the treatment of bipolar disorder with lithium, this study will include four phases of treatment. The first phase, the Efficacy Phase, will include participants being randomized to either lithium or placebo for 8 weeks to determine the efficacy of lithium in the treatment of children and adolescents with bipolar I disorder. Once participants complete the Efficacy Phase, participants may be eligible to continue in the Long- Term Effectiveness Phase for a maximum of 24 weeks of lithium treatment. Subsequently, participants meeting response criteria during the Long-Term Effectiveness Phase will be eligible to continue in the Discontinuation Phase. During the Discontinuation Phase, participants will be randomized to either placebo or lithium treatment for up to 28 weeks. Finally, those participants who experience a mood relapse during the Discontinuation Phase will be enrolled in an Open Label Restabilization Phase and treated with lithium for up to 8 weeks.
Inclusion criteria: inclusion criteria:

 Participants aged 7 years to 17 years, 11 months old at time of first dose

 Participants must meet DSM-IV diagnostic criteria, as assessed by a semi-structured assessment (KSADS-PL) and a separate clinical interview with a child/adolescent psychiatrist for manic or mixed episodes in bipolar I disorder

 Score of > 20 on the YMRS at screening and baseline

 The participant and legal guardian must understand the nature of the study and be able to comply with protocol requirements. The legal guardian must give written informed consent and the youth, written assent

 Participants with comorbid conditions [attention deficit hyperactivity disorder (ADHD), conduct disorder], except those listed in Exclusion Criterion 2, may participate

 If female: is premenarchal, or is incapable of pregnancy because of a hysterectomy, tubal ligation, or spousal/partner sterility. If sexually active and capable of pregnancy, has been using an acceptable method of contraception (hormonal contraceptives, intrauterine device, spermicide and barrier) for at least one month prior to study entry and agrees to continue to use one of these for the duration of the study. If sexually abstinent and capable of pregnancy, agrees to continued abstinence or to use of an acceptable method of birth control should sexual activity commence

 Has a negative quantitative serum ß-human chorionic gonadotrophin hormone pregnancy test at screening and a negative qualitative urine pregnancy test at baseline, if female

 Participants with a history of substance abuse may participate if they agree to continue to abstain from drugs during the trial and have a negative drug screen at screening or prior to baseline. Those with an initial positive drug screen during screening may have another screen done 1-3 weeks later while in screening, and a negative result will allow the participant to participate

 The participant is willing and clinically able to wash out of exclusion medications during the screening period. Prior to the administration of lithium, participants will have not used any of the following medications: antipsychotics, monoamine oxidase inhibitors, antidepressants within the preceding 2 weeks; stimulants within the preceding week; or fluoxetine or depot antipsychotics in the past month (no stable participants will be asked to discontinue medications)

 ECG and bloodwork including CBC, electrolytes, etc. (as per Safety assessment procedures listed in Table 6) showing no clinically significant abnormalities

Exclusion criteria: :

 Participant who is clinically stable on current medication regimen for bipolar disorder

 A current or lifetime diagnosis of Schizophrenia or Schizoaffective Disorder, a Pervasive Developmental Disorder (ASQ score > 15), Anorexia Nervosa, Bulimia Nervosa, or Obsessive-Compulsive Disorder

 Current DSM-IV diagnosis of Substance Dependence

 Positive drug screen at screening and on retest 1-3 weeks later

 Participants with symptoms of mania that may be attributable to a general medical condition, or secondary to use of medications (e.g., corticosteroids)

 Evidence of any serious, unstable neurological illness for which treatment under the auspices of this study would be contraindicated

 Any serious, unstable medical illness or clinically significant abnormal laboratory assessments that would adversely impact the scientific interpretability or unduly increase the risks of the protocol

 Current general medical condition including neurological disease, diabetes mellitus, thyroid dysfunction, or renal dysfunction that might be affected adversely by lithium, could influence the efficacy or safety of lithium, or would complicate interpretation of study results

 Evidence of current serious homicidal/suicidal ideation such that in the treating physician's opinion it would not be appropriately safe for the participant to participate in this study

 Evidence of current active hallucinations and delusions such that in the treating physician's opinion it would not be appropriately safe for the participant to participate in this study

 Concomitant prescription of over-the-counter medication or nutritional supplements (e.g., ibuprofen, naproxen, St John's wort) that would interact with lithium or affect the participant's physical or mental status

 Concomitant psychotherapy treatments provided outside the study initiated within 4 weeks prior to screening

 Previous adequate trial with Li+ (at least 4 weeks with Li+ serum levels between 0.8-1.2 mEq/L)

 History of allergy to lithium or lithium intolerance

 Psychiatric hospitalization within 1 month of screening for psychosis or serious homicidal/serious suicidal ideation

 Clinician's judgment that participant is not likely to be able to complete the study as an outpatient due to psychiatric reasons

 Females who are currently pregnant or lactating

 Sexually active females who, in the investigators' opinion, are not using an adequate form of birth control.

 Participants who are unable to swallow the study medication

 Participants for whom a baseline YMRS score of < 20 is anticipated

 Participants with an IQ less than 70 (determined using the Wechsler Abbreviated Scales of Intelligence {WASI} Vocabulary and Matrix Reasoning Subscales)


Comparing Daily vs Intermittent Regimen of ATT in HIV With Pulmonary Tuberculosis

Summary: Acquired Rifampicin Resistance has emerged as an important issue in the treatment of HIV-TB patients. It has not been a major problem in HIV-negative individuals treated for TB treated with standard intermittent regimens. The study would generate data on the efficacy of daily and thrice weekly regimen of ATT in pulmonary TB patients with HIV in the presence of highly active antiretroviral therapy (HAART). Not many trials have compared sputum conversion and adverse drug reaction between daily and intermittent regimens of ATT in HIV positive patients. This study provides a unique opportunity for comparison of daily and intermittent therapy for HIV patients with pulmonary TB looking into multiple dimensions of HIV-TB treatment namely efficacy, drug resistance, toxicity , drug interaction and immune reconstitution inflammatory syndrome. The primary outcome of the study is to compare the efficacy of three anti-TB regimens in a) reducing bacteriological failures and b) decreasing the emergence of Acquired Rifampicin Resistance (ARR). The secondary outcomes include unfavourable responses (clinical failures, deaths, relapses) as whole, treatment emergent adverse drug reactions, pharmacokinetic levels of ATT and incidence of immune reconstitution syndrome.
Inclusion criteria: inclusion criteria:

 Age above 18 years.

 HIV-1/2 infected patients with Pulmonary TB. This includes sputum smear positive disease.

 Initially smear negative but Xpert-MTB positive or LPA positive taken as a surrogate marker for culture positivity (e.g. miliary TB, Mediastinal adenitis and Chest x-ray with persistent abnormality after antibiotics). as BACTEC (Becton-Dickinson) has been phased out ,Final inclusion will only be patients positive by LJ culture

 Persistent X-ray abnormality will be included for allocation. However final inclusion into both ITT and efficacy analysis will depend on positivity in LJ culture.

 Living within 40 km radius from the nearest sub centre of TRC and willing for attendance as prescribed.

 Likely to remain in the same area for at least one and half years after start of treatment.

 Willing for house visits and surprise checks.

 Willing to participate and give informed consent after going through the terms and conditions of the trial.

Exclusion criteria: :

 Patients with known hypersensitivity to rifampicin

 Pregnancy and lactation at initial presentation

 Major complications like HIV encephalopathy, renal dysfunction (serum creatinine > 1.5 mg% in the absence of dehydration) or jaundice (serum bilirubin > 2 mgs% along with SGOT /SGPT elevation > 2.5 times the upper limit of normal).

 Previous anti-tuberculosis treatment for more than 1 month. Prophylaxis (non-rifampicin containing regimen) will not be considered as prior antituberculosis treatment.

 Moribund, bedridden or unconscious patients.

 Co-morbid conditions like uncontrolled diabetes mellitus, cardiac failure, and malignancy at initial presentation.

 Major psychiatric illness.

 Patients on second line ART, mainly protease inhibitors, at initial presentation.

['ATT (Ethambutol, Pyrazinamide, INH, Rifampicin)']

ATT (Ethambutol
Pyrazinamide
INH
Rifampicin)


Study to Investigate the Performance of Cervical Arthroplasty for the Treatment of Cervical Degenerative Disc Disease

Summary: The purpose of the study is to evaluate the performance of the Discover cervical Artificial disc in the treatment of degenerative disc disease in one level of the cervical spine.
Inclusion criteria: inclusion criteria:

 Male or female subjects, aged between 18 and 65 years inclusive.

 Subjects who are able to give voluntary, written informed consent to participate in this clinical investigation and from whom consent has been obtained.

 Subjects who, in the opinion of the Clinical Investigator, are able to understand this clinical investigation, co-operate with the investigational procedures and are willing to return to the hospital for all the required post-operative follow-ups.

 Objective evidence of cervical disc disease in one vertebral level between C3-C7 defined as one or more of the following:

 Shoulder and/or arm pain in a radicular distribution resulting from herniated disc or bony osteophytes (Consistent w diagnostic imaging including Axial CT, CT Myelogram, MRI and/or plain films)

 Subjects with myeloradiculopathy resulting from mild spinal cord compression and nerve root impingement

 Unresponsive to documented non-surgical management for ≥ 6 weeks and/or presents with progressive symptoms of nerve root or spinal cord compression in the face of continued non-surgical management (e.g., physical therapy, medication therapy, corticosteroid injections, etc.)

 Minimum Neck Disability Index score of ≥30 % (15/50 points)

Exclusion criteria: :

 Subjects who, in the opinion of the Clinical Investigator, have an existing condition that would compromise their participation and follow-up in this clinical investigation.

 Subjects who are pregnant, lactating or wishes to become pregnant within the duration of the study.

 Subjects who are known drug or alcohol abusers or with psychological disorders that could affect follow-up care or treatment outcomes.

 Subjects who have participated in a clinical investigation with an investigational product in the last 30 days.

 Subjects who are currently involved in any injury litigation claims.

 Subjects with significant degeneration at more than one cervical level (e.g. DISH, ankylosing spondylitis, congenital abnormality, rheumatoid arthritis)

 Subjects who have had any prior surgery at the level to be treated (subjects with a prior Laminotomy at the level to be treated may be included in the study)

 Subjects who have marked cervical instability on lateral or flexion/extension x-rays defined as translation ≥3mm and/or ≥11 degrees of rotational difference to either adjacent level

 Subjects who have presence of systemic infection or infection at the site of surgery

 Subjects who have been diagnosed with malignancy

 Subjects who have been diagnosed with a condition or require postoperative medication(s) that may interfere with bony/soft tissue healing

 Subjects who have been diagnosed with Osteoporosis, Osteopenia, other metabolic bone disease or endocrine disorder known to affect osteogenesis.

 Subjects with pre-existing neurological abnormalities other than deficits produced from the spinal lesion (e.g., MS, Parkinson's, CVA, diabetic neuropathy, peripheral neuropathy).

 Subjects with morbid obesity defined as a BMI of ≥40, or more than 100 lbs (45.4kg) over ideal weight.

 Subjects with any known allergy to titanium metal, polyethylene, metal alloy or carbon fibre reinforced polymer

 Subjects who have had prior fusion surgery at any level(s) (C1-T1)

 Subjects with kyphosis >-15 degrees evaluated using the Cobb angle measurement

 Subjects with Significant cervical degenerative disease characterized by bridging anterior osteophytes, significant loss of disc space height (3mm or less), sclerotic facets, large posterior osteophytes, autofusion of other cervical levels, and degenerative retrolisthesis. Spinal diseases such as DISH, ankylosing spondylitis, congenital abnormality, and rheumatoid arthritis, should also be excluded

 Subjects undergoing treatment with a bone growth stimulator, which cannot be discontinued prior to enrollment in the study.

 Significant kyphotic deformity or significant reversal of lordosis.

['DISCOVER™ Artificial Cervical Disc', 'ACDF']


Outcomes of Different Thyroid Resections for Multinodular Non-toxic Goiter

Summary: The aim of this three-arm randomized study was to evaluate results of different thyroid resection modes among patients with bilateral multinodular non-toxic goiter, with special emphasis put on recurrence rate and morbidity rate, in a 5-year follow-up.
Inclusion criteria: Inclusion Criterion

 a bilateral non-toxic multinodular goiter with normal appearing on ultrasound of the neck posterior aspects of both thyroid lobes.

Exclusion criteria: :

 multinodular goiter involving posterior aspect/s of thyroid lobe/s,

 suspicion of thyroid cancer,

 previous thyroid surgery,

 thyroiditis,

 subclinical or clinically overt hypothyroidism or hyperthyroidism,

 pregnancy or lactation,

 age < 18 years or > 65 years,

 ASA 4 grade (American Society of Anesthesiology),

 inability to comply with the follow-up protocol.

['Total thyroidectomy', 'Dunhill operation', 'Bilateral subtotal thyroidectomy']

Total thyroidectomy
Dunhill operation
Bilateral subtotal thyroidectomy


Rituximab and Belimumab for Lupus Nephritis

Summary: In this experimental study, researchers will try to find out if treatment of lupus nephritis with a combination of rituximab and cyclophosphamide (CTX), or a combination of rituximab and CTX followed by treatment with belimumab is safe and if this drug combination can block the immune system attacks.
Inclusion criteria: inclusion criteria:

 Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria.

 Positive antinuclear antibody (ANA) or positive anti-ds DNA test results at visit -1 or any time within 14 days before visit -1.

 Active proliferative lupus nephritis, as defined by either of the following:

 Kidney biopsy documentation within the last 3 months of International Society of Nephrology/Renal Pathology Society (ISN/RPS) proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV.

 Active urinary sediment and kidney biopsy documentation within the last 12 months of ISN/RPS proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV. Active urinary sediment is defined as any one of the following:

 >5 RBC/hpf in the absence of menses and infection;

 >5 White blood cell per high powered field (WBC/hpf) in the absence of infection; or

 Cellular casts limited to RBC or WBC casts.

 Urine protein-to-creatinine ratio (UPCR) >1 at study entry based on a 24-hour collection.

 Ability to provide informed consent.

Exclusion criteria: :

 New onset lupus nephritis, defined as lupus nephritis for which the participant has not yet been treated with either mycophenolate mofetil or cyclophosphamide.

 Neutropenia (absolute neutrophil count <1500/mm^3).

 Thrombocytopenia (platelets <50,000/mm^3).

 Moderately severe anemia (Hgb < mg/dL).

 Moderately severe hypogammaglobulinemia (IgG <450 mg/dL) or Immunoglobulin A (IgA) <10mg/dL.

 Positive QuantiFERON -Tuberculosis (TB) Gold test results.

 Pulmonary fibrotic changes on chest radiograph consistent with prior healed tuberculosis.

 Active bacterial, viral, fungal, or opportunistic infections.

 Evidence of infection with human immunodeficiency virus (HIV), hepatitis B (as assessed by HBsAg and anti-HBc) or hepatitis C.

 Hospitalization for treatment of infections, or parenteral (IV or IM) antibacterials, antivirals, anti-fungals, or anti-parasitic agents within the past 60 days.

 Chronic infection that is currently being treated with suppressive antibiotic therapy, including but not limited to tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria.

 History of significant infection or recurrent infection that, in the investigator's opinion, places the participant at risk by participating in this study.

 Receipt of a live-attenuated vaccine within 3 months of study enrollment.

 End-stage renal disease (eGFR <20 mL/min/1.73m^2).

 Concomitant malignancies or a history of malignancy, with the exception of adequately treated basal and squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.

 History of transplantation.

 History of primary immunodeficiency.

 Pregnancy.

 Breastfeeding.

 Unwillingness to use an FDA-approved form of birth control (including but not limited to a diaphragm, an intrauterine device, progesterone implants or injections, oral contraceptives, the double-barrier method, or a condom).

 Use of cyclophosphamide within the past 6 months.

 Use of anti-Tumor Necrosis Factor (TNF) medication, other biologic medications, or experimental non- biologic therapeutic agents within the past 90 days, or 5 half-lives prior to screening, whichever is greater.

 Intravenous immunoglobulin (IVIG), plasmapheresis, or leukopheresis within the past 90 days.

 Use of investigational biologic agent within the past 12 months.

 Prior treatment with rituximab, belimumab, atacicept, or other biologic B cell therapy.

 Liver function test [aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase] results that are >=2 times the upper limit of normal.

 Severe, progressive, or uncontrolled renal, hepatic, hematological,gastrointestinal, pulmonary, cardiac, or neurological disease, either related or unrelated to SLE, with the exception of active lupus nephritis (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study).

 Comorbidities requiring corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the previous 12 months.

 Current substance abuse or history of substance abuse within the past year.

 History of severe allergic or anaphylactic reactions to chimeric or fully human monoclonal antibodies.

 History of anaphylactic reaction to parenteral administration of contrast agents.

 Lack of peripheral venous access.

 History of severe depression or severe psychiatric condition.

 History of suicidal thoughts within the past 2 months or suicidal behavior within the past 6 months, or a significant suicide risk in the investigator's opinion.

 Inability to comply with study and follow-up procedures.

['Rituximab', 'Cyclophosphamide', 'Prednisone', 'Methylprednisolone', 'Diphenhydramine', 'Acetaminophen', 'Rituximab', 'Cyclophosphamide', 'Prednisone', 'Methylprednisolone', 'Diphenhydramine', 'Acetaminophen', 'Belimumab']

Rituximab Cyclophosphamide Prednisone Methylprednisolone Diphenhydramine Acetaminophen Rituximab Cyclophosphamide Prednisone Methylprednisolone Diphenhydramine Acetaminophen Belimumab


Comparative Study of Colon Capsule and Virtual Colonoscopy (VICOCA)

Summary: Summary Colorectal cancer (CRC) represents the second leading cause of cancer deaths in Spain (11,000 deaths per year). Screening of the population over 50 years of age with no significant history (intermediate risk) is recommended, but which screening method is best for promoting adherence in this type of patient has not been well established. There are currently two screening methods that are less invasive than conventional colonoscopy and seem to have higher sensitivity than the test for faecal occult blood (FOBT). These two methods are the colon capsule, which consists in ingesting a capsule that takes photographs of the colon, and virtual colonoscopy, which is a radiological technique.~Objectives: 1. To demonstrate that virtual colonoscopy and colon capsule are effective CRC screening techniques in the intermediate risk population, with diagnostic rates comparable to conventional colonoscopy (concordance). 2. To compare the diagnostic rates of the colon capsule and virtual colonoscopy with respect to the size and characteristics of the lesions visualised. 3. To compare the participation rates for each screening strategy and identify the factors that influence participation (individual, family, and socioeconomic factors as well as those relating to the doctor).
Inclusion criteria: inclusion criteria:

 The main objective in this study is compare two non-invasive techniques in the study of colorectal cancer. When we calculate the sample size we observed that we need more than 1000 patients per group. In this moment this study is very expensive and it is not feasible. Our proposal is include population with a higher prevalence of lesions: individuals with positive FIT (fecal immunochemical test) in which the prevalence of lesions is 60%. In this case, sample size is reduced considerably.

 The eligible population will be men and women, 50-69 years old, with no known risk factors and positive FIT.

Exclusion criteria: :

 Individuals who have symptoms suggestive of colorectal disease (rectorrhagia, change in bowel movement frequency, constitutional syndrome, anaemia).

 History of inflammatory bowel disease, colorectal polyposis, colorectal adenoma or CRC, and total or partial colectomy.

 History of familial adenomatous polyposis or other hereditary polyposis syndromes; hereditary colorectal cancer not associated with polyposis (diagnosed by the presence of germinal mutation in the DNA repair genes and/or by fulfilment of the Amsterdam II criteria);

 Severe co-morbidity that carries a poor short-term prognosis (disease with an average life expectancy of less than 5 years) or a chronic illness that involves significant limitation of physical activity.

 Contraindication to undergoing colon capsule or virtual colonoscopy.


Clinical Trial to Evaluate Ultrasonic Surgical Device in Chronic Pressure Ulcer

Summary: Study objective The purpose of this trial is to evaluate the efficacy and safety of the investigational device, ULSD-12D, as Compared to the comparator, SONOCA-180, in chronic wound.
Inclusion criteria: inclusion criteria:

 over 20 years of age

 subject who has untreated wounds

 subject who has wound size over 3cm x 3cm

 subject who has wound over stage 2

Exclusion criteria: :

 cellulitis


Rifaximin for Preventing Relapse of Clostridium Associated Diarrhoea

Summary: Clostridium difficile associated diarrhoea is an important cause of morbidity in patients treated with antibiotics, especially in hospital. Clinical relapse occurs after up to 30% of initially successful treatments for colitis. Preliminary reports suggest that Rifaximin, a poorly absorbed antibiotic used to treat travellers diarrhoea can prevent relapse. We plan to carry out a randomised placebo controlled trial to test the hypothesis that Rifaximin given in a reducing dose over 4 weeks after successful treatment will reduce the relapse rate.
Inclusion criteria: inclusion criteria:

 Men / Women aged 18 and over (We will also include those adults who lack mental capacity for whom we have a legal representative)

 Successful treatment of clinically diagnosed CDAD using standard therapy (metronidazole or vancomycin given according to standard local hospital guidelines).

Exclusion criteria: :

 Woman of child bearing potential and not willing to use at least one highly effective contraceptive method throughout the study

 Male with spouse/partner of child bearing potential and not willing to use condoms

 Pregnant or breast feeding

 Unable to swallow tablets

 Life expectancy of <4 weeks

 Hypersensitivity to the active substance, to any rifamycin (e.g. rifampicin or rifabutin) or to any of its excipients (Tablet core: Sodium starch glycolate type A, glycerol distearate, colloidal anhydrous, silica, talc and microcrystalline cellulose. Tablet coating: hypromellose, titanium dioxide (E171), disodium edentate, propylene glycol and red iron oxide E172)

 >5 days post standard therapy (metronidazole or vancomycin) for clinically diagnosed CDAD

 Taking ciclosporin


Interacting Together Everyday: Recovery After Childhood Traumatic Brain Injury (TBI) I-InTERACT

Summary: The purpose of this study is to test an on-line intervention for families of young children who have experienced moderate or severe traumatic brain injury (TBI). Previous interventions were not designed to address the needs of young children with TBI, and feedback revealed a desire for more examples and materials appropriate for families of younger children. This project builds upon the investigators previous research by modifying the online intervention content to address the needs of young children with TBI. The goal of this project is to develop an intervention that will encourage positive parenting behaviors, improve child behaviors, and reduce parent distress and burden following TBI. The investigators hypothesize that the intervention group will exhibit more effective parenting skills as well as better child functioning and lower levels of parental distress at follow-up than will the active comparison group.
Inclusion criteria: inclusion criteria:

 Moderate to severe TBI that occurred within the last 24 months

 Overnight hospital stay

 English-speaking

 Parent must be willing to provide informed consent

Exclusion criteria: :

 Child does not live with parents or guardian

 Child or parent has history of hospitalization for psychiatric problem

 Diagnosed with moderate or severe mental retardation, autism, or a significant developmental disability

['Internet-based Interacting Together Everyday: Recovery After Childhood TBI', 'Internet Resources Comparison']


Feasibility of Pharmaceutical Interventions in Elderly Heart Failure Patients.

Summary: Heart failure therapies (e.g. beta blockers) have been successful in decreasing mortality rates, as well as diminishing hospitalizations. Also, pharmacist collaboration has been shown to have a beneficial impact on heart failure related outcomes. Regardless, a high residual event rate is to be noted.~In our pilot study, we wished to document whether a clinical pharmacist could still play a role in the heart failure management of an elderly inpatient heart failure population.
Inclusion criteria: inclusion criteria:

 75 years or older

 diagnosis of previous or new heart failure based on signs and symptoms as defined by the 'European Society of Cardiology guidelines on acute and chronic heart failure'

 diagnosis had to be confirmed by a recent echocardiogram

Exclusion criteria: :

 not Dutch speaking

 treatment restrictions had been applied on admission

['heart-failure related pharmaceutical intervention']


Surgical Treatment of Low Energy Pelvic Fractures in the Elderly

Summary: Since May 2010 the Department of Trauma, Basel University Hospital has performed surgical stabilisation of the posterior pelvic ring on 55 patients. These patients have not received a structured follow up examination or evaluation of outcome after surgery.
Inclusion criteria: inclusion criteria:

 Elderly patients (age ≥55y ears) of any ethnic / sociodemographic background

 Pelvic ring fracture after low energy trauma affecting the posterior ring or both (posterior and anterior ring)

 Surgical stabilisation of the pelvic ring at Basel University Hospital between May 2010 and December 2014

 Ambulatory before surgery

 Informed consent for study participation by the patient or legal representatives

Exclusion criteria: :

 Refusal of consent by the patient or legal representatives to participate in the study

 Fractures within the last 3 months before follow-up

 Suspicion of a pathological fracture in the context of known or unknown malignancy

 Symptomatic low back pain with morphological changes, i.e. intervertebral disc displacement, neoplasm metastasis in the axial skeleton, spinal stenosis, vertebral fracture, spondylarthropathy etc.

 Pre-trauma mobility status that precludes achieving a post-trauma mobility status enabling the patient to perform the timed up and go test (e.g. patient in a wheel chair)


Study of Quinvaxem for Vaccination Against Diphtheria, Pertussis, Tetanus, Hepatitis B and Diseases Caused by Haemophilus Influenzae Type B

Summary: The aim of this study was to evaluate the immunogenicity and safety of the Quinvaxem vaccine (a liquid combination vaccine against diphtheria, tetanus, B. pertussis, hepatitis B and H. influenzae Type B). Healthy Vietnamese infants received three doses of vaccine at 2, 3 and 4 months of age according to the local Expanded Programme on Immunisation (EPI) schedule
Inclusion criteria: inclusion criteria:

 Infants are at age of DTP vaccination of the local EPI program (60-120 days old) and free from any obvious health problems

 Have a normal gestational age (≥ 37 weeks); birth weight > 2.5 kg

 There is no congenital disease detected through interview and clinical examination

 Already had or not yet received Hepatitis B vaccination at birth

 Do not have dermatological diseases such as eczema, allergies

 Parent or legal guardian voluntarily provides consent for their child for participation in the study by signing the informed consent and agrees to comply with all study procedures

Exclusion criteria: :

 Already vaccinated with DTP vaccine

 Have an acute infection at the time of study vaccination

 Contraindications to Quinvaxem

 Receiving treatment with systemic corticosteroids

 Currently participating in another clinical trial

 In receipt of a parenteral immunoglobulin preparation and/or blood/blood products since birth

 Parents intend to move to another location during the study (the next 12 months)

['Diphtheria', 'Pertussis', 'Tetanus', 'Hepatitis B', 'Haemophilus Influenzae Infections']

Diphtheria
Pertussis
Tetanus
Hepatitis B
Haemophilus Influenzae Infections


Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH)

Summary: The purpose of this study is to determine if vaginal estrogen use is associated with resolution of blood in the urine (microscopic hematuria) in postmenopausal women. The hypothesis is that postmenopausal women with blood in the urine (microscopic hematuria) will have higher rates of resolution of hematuria after treatment course with vaginal conjugated equine estrogen cream compared to placebo cream
Inclusion criteria: inclusion criteria:

 Post-menopausal women

 Asymptomatic microscopic hematuria (three or more red blood cells per high powered field on a single urine microscopy) in the absence of urinary tract infection.

Exclusion criteria: :

 Known urologic disease

 Presence of gross hematuria

 Presence of indwelling urologic foreign body (foley catheter, ureteral stent)

 Inability to obtain intravenous contrast CT scan (elevated creatinine, severe contrast allergy)

 History of pelvic irradiation or malignancy

 Not a candidate for vaginal estrogen

 Allergy to vaginal estrogen

 Current or prior diagnosis of breast or endometrial cancer

 History of deep vein thrombosis/pulmonary embolus

 Hypercoagulable state

['Premarin vaginal estrogen cream', 'Placebo vaginal cream']

Premarin vaginal estrogen cream
Placebo vaginal cream


Nasal Versus Venous Lorazepam for Control of Acute Seizures in Children

Summary: Status epilepticus (SE) is a common pediatric emergency which is potentially life-threatening and requires rapid termination. Early and effective treatment is essential to prevent the morbidity and mortality associated with prolonged convulsive SE. Lorazepam is the standard of care for control of SE when administered by intra-venous (IV) route. The investigators intend to compare efficacy and adverse effect profile of intra-nasal vs. intravenous routes of administration of lorazepam. In resource poor settings, sometimes trained personnel or appropriate equipment for intra-venous cannulation is not available. Alternate routes of administration, if shown equivalent to conventional IV route, will be very useful in such settings or for out of hospital management of seizures in children.
Inclusion criteria: inclusion criteria:

 Children presenting convulsing to the pediatric emergency or developing seizure while in casualty

 Age 6-14 years

Exclusion criteria: :

 Known hypersensitivity to any benzodiazepine

 Child has received any parenteral anti-convulsant within 1 hr prior to enrollment

 Presence of severe cardio-respiratory compromise or cardiac arrhythmias

 Presence of upper respiratory tract infection

 Presence of basal skull fracture causing cerebro-spinal fluid (CSF) rhinorrhea


A Prospective Study of Risperdal (Risperidone) for the Treatment of Behavioral Disorder Following Psychological Therapy for Challenging Behavior in Learning Disabled Children

Summary: The purpose of this study is to assess whether risperidone (an antipsychotic medication) is safe and effective in treating behaviour disorder in learning disabled children, which does not improve with psychological therapy.
Inclusion criteria: inclusion criteria:

 DSM-IV Axis II diagnosis of mental retardation

 behavioural and family therapy tried for 6 months but has failed

 in school, at least part time

 score of >=8 on hostility scale

 subject is otherwise healthy

Exclusion criteria: :

 Patients with a seizure disorder requiring repeated change of medication

 extrapyramidal symptoms not well controlled by medication

 abnormal and clinically significant electrocardiogram (ECG) changes

 history of tardive dyskinesia (a condition of uncontrollable movements of the tongue, lips, face, trunk, hands and feet that is seen in patients receiving long-term medication with certain types of antipsychotic drugs), or neuroleptic malignant syndrome (a rare condition in patients receiving antipsychotic medication in which patients may develop fever, sweating, unstable blood pressure, rigid muscles, and other symptoms, including changes in their normal mental state)

 known hypersensitivity to antipsychotic medications, including risperidone.

['Learning Disorders', 'Child Behavior Disorders']

Learning Disorders
Child Behavior Disorders


Guided Imagery and Music for the Reduction of Side Effects of Chemotherapy in Teenagers

Summary: The purpose of this study is to determine whether a modified and resource-oriented form of Guided Imagery and Music (GIM) is effective in reducing side effects of chemotherapy in teenagers with cancer.
Inclusion criteria: inclusion criteria:

 Teenagers at the ages 12-17

 Four or five (dependent on their overall plan of medical treatment) consecutive courses of chemotherapy administrated at the involved child cancer units and (administered) over a period of minimum 24 hours incl. hydration with assumed moderate to severe nausea and vomiting.

 The specific type of chemotherapy may vary across the four/five consecutive courses but shall include one of the following moderate and/or highly emetogenic types of chemotherapy:

 Moderate emetogenic chemotherapy:

 Carboplatin

 Cyclophosphamide <1500 mg/m2

 Cytarabine >1 g/m2

 Daunorubicin

 Doxorubicin

 Epirubicin

 Idarubicin

 Ifosfamide

 Mitoxantrone

 Methotrexate >1000 mg/m2

 Highly emetogenic chemotherapy:

 Cisplatin >25 mg/m2

 Cyclophosphamide >1500 mg/m2

 Dacarbazine

 Understand Norwegian/Danish

 Read Norwegian/Danish (teenagers or alternatively parents)

 No significant hearing impairment

 Informed written consent (teenagers ≥16 years and parents)

 Subsequent verbal confirmation of written informed consent before enrolment in study

Exclusion criteria: :

 Previous and/or acute psychiatric diagnosis

 Cognitive and mental deficits or impaired functioning


Fermented Iron-rich Supplement in Reducing Anemia

Summary: The consequences of iron deficiency anemia in women are enormous, and especially in developing countries, as the condition adversely affects both their productive and reproductive capabilities. The study seeks to: 1) compare changes in iron status indicators among women receiving an iron-rich organic food supplement versus ferrous sulfate supplement, and 2) determine the suitable level of food supplement needed to prevent/reduce iron deficiency anemia among women in developing country settings.~A double-blind, randomized, controlled, intervention trial will be implemented in women of childbearing age, 60 women with iron deficiency anemia and 60 women with iron deficiency. After screening potential subjects (up to 500 expected), approximately 30 will be recruited into each of four study groups; assuming 30% dropout rate, to detect an increase of 30% in ferritin as significant between the two time points at 80% power and alpha value of 0.05. Subjects who meet the inclusion criteria will be randomized into the four groups consisting of: 2 control groups (daily 60mg ferrous sulfate (FS-60) or daily 10mg ferrous sulfate (FS-10)), and 2 test groups (daily 60mg iron-rich supplement (IRS-60) or 10mg iron-rich supplement (IRS-10)). Subjects will take daily FS-60 and IRS-60 under supervision for 8 weeks while subjects taking FS-10 and IRS-10 will take the supplement under supervision for 12 consecutive weeks.
Inclusion criteria: inclusion criteria:

 18-49 years

 Regular menstruation in the last three months

 Hemoglobin <12 mg/dl;

 Serum Ferittin<20mcg/L

 BMI 18.5Kg/m^2 to 29.9 kg/m^2

Exclusion criteria: :

 history of gastrointestinal or hematological disorders,

 taking medications that could interfere with hematopoiesis or dietary iron absorption

 pregnant (based on pregnancy test).

['supplement containing 60 mg iron sulfate', 'iron rich food supplement (60 mg iron)', 'iron rich food supplement (10 mg iron)', 'supplement containing 10 mg iron sulfate']


Effects of Oropharyngeal Strengthening on Dysphagia in Patients Post-stroke

Summary: The overall goal of this randomized controlled pilot study is to characterize effects of SwallowSTRONG® Device-Facilitated Isometric Progressive Resistance Oropharyngeal (DF I-PRO) therapy in a dose response framework on swallowing-related outcomes in a group of unilateral ischemic stroke patients. These results will be used to determine adequate sample size in order to support a larger clinical trial focused on the efficacy of this therapy approach for improving swallowing safety. The first aim is to determine differences in swallowing physiology and bolus flow measures a) between a group of unilateral ischemic stroke subjects undergoing SwallowSTRONG® DF I-PRO therapy and controls and b) between 8 and 12 weeks of treatment. The second aim is to examine changes in level of oral intake and swallowing quality of life in post-stroke patients undergoing DF I-PRO therapy as compared to a control group and as they relate to treatment duration response at 8 weeks and 12 weeks. The third aim is to evaluate effects of DF I-PRO therapy on overall health status reflected by the number of pneumonia diagnoses and overall hospital readmission rates in post-stroke subjects undergoing DF I-PRO therapy compared to controls.
Inclusion criteria: inclusion criteria:

 clinical diagnosis of unilateral ischemic strokes by attending physician (according to the National Institute of Health Stroke Scale (NIHSS))

 within 6 months of acute stroke diagnosis

 a score of 3 or higher on the Penetration-Aspiration scale OR a score of 2 on the Residue scale at any location (oral cavity, valleculae, or pharynx) that is instrumentally documented by a participating SLP during a standardized videofluoroscopic swallowing study

 between the ages of 21 and 95

 ability to perform the strengthening protocol independently or with the assistance of a caregiver

 physician approval of medical stability to participate

 decision-making capacity to provide informed consent (confirmed through discussion with the subject's primary physician)

 phone access

 ability to return to the clinic for required follow-up appointments.

Exclusion criteria: :

 degenerative neuromuscular disease

 prior or current diagnosis of bilateral or hemorrhagic stroke

 prior surgery to the head and neck region that would affect muscles involved in swallowing

 history of radiotherapy or chemotherapy to the head and neck

 patient unable to complete the exercise program

 taking medications that depress the central nervous system

 allergy to barium (used in videofluoroscopic swallowing assessment)

 currently pregnant.

['Isometric Progressive Resistance Oropharyngeal Therapy', 'Compensatory approaches']


Transcranial Magnetic Stimulation and Anti-epileptic Effect: Optimization and Evaluation With Electrophysiology.

Summary: Epileptic disease is characterised by enhanced brain excitability. Low frequency repetitive transcranial magnetic stimulation (rTMS) can be an effective treatment for refractory frontal epilepsy. Thought, physiological mechanisms of its effectivity are still unknown. It is yet possible to evaluate cortical excitability and inhibition with TMS-coupled electromyography before and after rTMS sessions ; this could provide clues for basic mechanisms of rTMS effects on the epileptic brain. We assume that rTMS decrease brain excitability by improving brain inhibition. Such an information could help for treating patients with both pharmacological and non-pharmacological methods.
Inclusion criteria: inclusion criteria:

 Cryptogenic frontal lobe epilepsy

 Normal cerebral MRI
Exclusion criteria:

['cortical magnetic stimulation provided by an eight-shaped coïl placed upon the skull.']


Acute Coronary Syndrome and Care-Seeking Delay: A Web Based Behavioral Study

Summary: The primary aim of this study is to increase our understanding of care-seeking behavior surrounding heart attacks or acute coronary syndromes [ACS]. This study uses an internet based survey to ask individuals how they obtained medical care in the midst of a heart attack. At present, care-seeking delay among individuals stricken with a heart attack prevents them from obtaining the full therapeutic benefit of hospital based medical care in a timely manner to reduce the long term health consequences of a heart attack. By using a self-tailoring survey instrument the study attempts to take into consideration the complex social processes by which the individual and their family make decisions to seek medical care for symptoms of a heart attack. The study is designed to obtain a national sample of ACS care-seeking behavior in the United States.
Inclusion criteria: inclusion criteria: Acute myocardial infarction, acute coronary syndrome, unstable angina, men & women, all races & ethnicities

 -

Exclusion criteria: : age < 21 years

['Acute Myocardial Infarction', 'Heart Attack', 'Acute Coronary Syndrome', 'Unstable Angina']

Acute Myocardial Infarction
Heart Attack
Acute Coronary Syndrome
Unstable Angina


Assessment of Fluid Responsiveness by Elevation of PEEP in Patients With Septic Shock

Summary: The aim of the study is to evaluate whether fluid responsiveness of the critically ill patient can be assessed by analysing the PEEP-induced hemodynamic effects to systolic blood pressure, pulse pressure, aortic blood flow, aortic time-velocity integral and left ventricular end diastolic area measured with transesophageal echocardiography (PEEP-test). The chances are compared to increase of CI after volume expansion (gold standard). In clinical practise, it would be especially relevant if PEEP-induced changes in arterial pressure variations could be used in evaluation of volume status and fluid responsiveness. However, as ECHO-derived variables are used in greater extent to guide the treatment with inappropriate evidence, the simultaneous registration of ECHO-derived hemodynamic measurements is essential in the study design.
Inclusion criteria: inclusion criteria:• Written informed consent by patient or relative

 Time in ICU < 48 hours

 Septic shock

 Pulmonary artery catheter and radial arterial catheter

 Age 18 - 75 years

 Sinus rhythm

 Need for norepinephrine over 0.1 ug/kg/min but otherwise hemodynamically stable i.e no need to change the dose over the last 15min period before the study

 Mechanical ventilation with sedation

 Pwcp <18 mmHg

Exclusion criteria: :

 Contraindication to elevation of PEEP ( elevated intracranial pressure, pulmonary hypertension or other contraindication )

 Contraindication to fluid challenge

 Contraindication to TEE

 Previous heart failure, heart valve stenosis of insufficiency


Efficacy, Safety, and Tolerability of Ambien (Zolpidem) in the Treatment of Children Ages 6 to 17 With Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia

Summary: There has been an increased interest in the association between ADHD and sleep disorders over the past years. A high incidence of sleep disturbance, ranging from 10% to 70%, has been identified in ADHD children regardless of whether or not they are receiving stimulant therapy. This study will assess the safety and efficacy of zolpidem in children with ADHD associated insomnia.
Inclusion criteria: inclusion criteria:

 Male or female between the ages of 6 and 17 years, inclusive

 Children with diagnosed ADHD (as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision [DSM-IV-TR] criteria)

 Complaint of childhood insomnia as defined by repeated difficulty with sleep initiation or consolidation that occurs despite adequate age, appropriate time, and opportunity for sleep

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

 Subjects should be stabilized on all long-term therapy, including treatment of ADHD, for at least one month prior to study entry.

 Subjects, if females of childbearing potential (as determined by the initiation of menses), must have confirmed negative pregnancy test prior to randomization and be using a recognized effective method of birth control (oral, implant, depot or transdermal oestroprogestatives, intrauterine device, double-barrier with spermicide). Abstinence is an acceptable method of birth control for this study.

Exclusion criteria: :

 Mental retardation

 Autistic spectrum disorder

 A history of sleep apnea

 A history of bipolar disorder, conduct disorder, major depression, or generalized anxiety disorder (not obsessive compulsive disorder), as determined by clinical interview and DSM-IV-TR criteria

 Current history of substance abuse/dependence

 Known hypersensitivity to zolpidem or previous adverse experience with zolpidem

 Pregnant or breast-feeding

 Current use of hypnotics, antihistamines, melatonin, herbal products, or other sleep aids

['Attention Deficit Hyperactivity Disorder']


Lung Function Tests in Adolescents With Anorexia Nervosa

Summary: The investigators hypothesize that lung function would be adversely affected at the hypocaloric stage of adolescents suffering from anorexia nervosa.
Inclusion criteria: inclusion criteria:

 Adolescents with anorexia nervosa

 Ability to preform lung function tests

 Parents signing informed concent and adolescents signing informed ascent

Exclusion criteria: :

 A history of a lung disease

 Intercurrent lung illness


Improving Venous Thromboembolism Prophylaxis

Summary: Preventing the formation of blood clots in the veins so they do not injure leg veins or travel to the lungs, also called venous thromboembolism prophylaxis (VTE-P) is an essential component of safe in-patient care, yet it is deployed sub-optimally in many hospitals, including The investigators own. Two prior VTE-P improvement projects were completed at Mayo Clinic hospitals, one in the Department of Medicine, and the other in selected divisions of the Department of Surgery. Both projects resulted in marked improvement in the percentage of patients receiving appropriate VTE-P. This project seeks to utilize the lessons learned from these two pilots along with known best practices for "spreading" to deploy methods that enhance VTE-P to the entire hospitalized population. The investigators seek appropriate VTE-P rates exceeding 95%.
Inclusion criteria: inclusion criteria:

 Inpatients with age > 17 years old

Exclusion criteria: :

 Outpatients

 Inpatients with age less than or equal to 17 years old

['VTE-P Tollgate', 'BLAZE Pop up', 'Usual Care']

['Venous Thromboembolism', 'Delivery of Health Care', 'Quality Improvement']

Venous Thromboembolism
Delivery of Health Care
Quality Improvement


Tolerance and Efficacy Evaluation of 3 Face Creams

Summary: The study will evaluate the tolerance and the efficacy on skin comfort of F#1048-082 soothing cream used just after injection procedure and also the tolerance and the efficacy of the F#841-020 anti-age cream on aging parameters compared to baseline and to the F#1374-002 placebo cream (comparison within subjects - half face method) to identify additional benefits delivered by the product compared to a cosmetic procedure.
Inclusion criteria: inclusion criteria:

 female gender

 age > 35 years old

 good general state of health

 woman who had already undergone Hyaluronic acid injections

 woman who have not applied any retinoid product in the last 3 months

 woman who are not in a recovery period after laser/peeling/acne treatment

 accepting to return to the centre for the planned visits

 accepting to follow the investigator's instructions during the entire study period

 agreeing to present at each study visit without make-up

 accepting to not change their habits regarding: food, physical activity, face cleansing and make-up use

 agreeing to not receive any drug able to change the skin characteristics during the entire duration of the study

 accepting to not receive any cutaneous anti-age treatment during the entire duration of the study

 accepting not to expose their face to strong UV irradiation (UV session or sun bathes) during the entire duration of the study

 accepting to sign the Informed consent form.

Exclusion criteria: :

 Pregnancy (only for subjects not in menopause)

 lactation (only for subjects not in menopause)

 subjects not in menopause who do not use adequate contraceptive precautions in order to avoid pregnancies during the study;

 subjects not in menopause who do not accept to perform the pregnancy test during the basal visit (T0), 6 and 12 weeks after the intradermal implant execution;

 subjects participating to a similar test less than 3 months ago

 sensitivity to the test products or theirs ingredients

 subjects whose insufficient adhesion to the study protocol is foreseeable.

 dermatitis

 presence of cutaneous disease on the tested area as lesions, scars, malformations.

 clinical and significant skin condition on the test area (e.g. active eczema, dermatitis, psoriasis etc.)

 recurrent facial/labial herpes.

 diabetes

 endocrine disease

 hepatic disorder

 renal disorder

 cardiac disorder

 pulmonary disease

 digestive disease

 haematological disease

 chronic phlogosis or autoimmune disease

 cancer

 neurological or psychological disease

 drug allergy.

 systemic corticosteroids

 retinoid products in the previous 3 months and during the entire study period

 aspirin or non-steroid anti-inflammatory drugs (FANS)

 anti-histaminic, narcotic, antidepressant, immunosuppressive drugs (with except, for female subjects, of contraceptive or hormonal treatment starting from at least one year)

 assumption of drugs able to influence the test results in the investigator opinion.

['Soothing (formulation number: F#1048-082) and antiaging creams (F#841-020 and F#1374-002)']


Humoral and Cell Mediated Immunity and Safety of MF59C.1-adjuvanted Subunit Influenza Vaccine or a Conventional Subunit Influenza Vaccine in Previously Unvaccinated Healthy Subjects

Summary: This study aims to evaluate the immunogenicity, by means of cell mediated immunity (CMI) and hemagglutination inhibition (HI) assay, and also the safety of a MF59C.1-adjuvanted subunit influenza vaccine compared with a conventional subunit vaccine in previously unvaccinated children aged 6 to <36 months.
Inclusion criteria: inclusion criteria:

 Male and female previously unvaccinated healthy children aged 6 to <36 months.

Exclusion criteria: :

 Any known or suspected impairment of the immune system, any serious disease.

 Any subjects receiving licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.

 Individuals who have had influenza vaccine or documented suspected influenza disease prior to day 1.

['MF59C.1-adjuvanted subunit influenza vaccine', 'Sub unit, Inactivated, Influenza vaccine']

['Seasonal Influenza', 'Influenza', 'Influenza Due to Unspecified Influenza Virus', 'Human Influenza']


A Prospective Randomized Equivalence Trial to Evaluate the Safety of the Ligasure in Thyroid Surgery

Summary: This is a randomized, prospective equivalence trial on the safety of the Ligasure Vessel Sealing System as used in thyroid surgery. The Ligasure system is a hand held surgical device that uses heat to seal blood vessels during surgery. It has been a tested and accepted technology in abdominal surgery and it is now being applied to surgery of the thyroid gland because it is faster than the traditional method of tying blood vessels that a surgeon must do manually. To remove the thyroid gland safely the surgeon must dissect the gland away from the recurrent laryngeal nerve which controls the vocal cords and patient's voice. Protecting this nerve is the key step in all thyroid surgery as its damage can permanently alter a patient's voice and even obstruct the airway. At this time the worldwide accepted rate of nerve injury is 2 in 100 patients. The hypothesis of this study is that the nerve injury rates for surgery using the Ligasure device are similar to that seen when surgeons manually tie blood vessels. The investigators protocol will evaluate the function of the recurrent laryngeal nerve after removing the thyroid gland using the Ligasure device in comparison to the traditional method where the surgeon manually ties blood vessels. In this study, for patients undergoing total thyroidectomy for a benign condition, each patient will be randomized to have one lobe of thyroid (left or right) removed using manual tying of blood vessels and the other side will have the surgeon use the Ligasure device to seal blood vessels. Every patient has a pre- and post-operative independent assessment of vocal cord function using nasopharyngoscopy to ensure that the vocal cords are working normally prior to surgery and also to document vocal cord dysfunction if there is an injury to the recurrent laryngeal nerve. The investigators intent is to show that the Ligasure system is a safe method to sealing vessels in thyroid surgery and that the thermal dispersion of this device does not pose a significant increase in risk to the recurrent laryngeal nerve
Inclusion criteria: inclusion criteria:

 multinodular goiter

 Grave's disease

 thyroid nodule

Exclusion criteria: :

 thyroid carcinoma

 reoperative surgery

['Multinodular Goitre', "Grave's Disease", 'Thyroid Nodule']

Multinodular Goitre
Grave's Disease
Thyroid Nodule

:

 thyroid carcinoma

 reoperative surgery


Risk of Cardiovascular Events in Patients With Type 2 Diabetes Initiating Oral Antidiabetic Treatments

Summary: The purpose of this study is to compare the incidence of major cardiovascular events among patients with type 2 diabetes who are new initiators of Saxagliptin and those who are new initiators of oral anti-diabetic drugs (OADs)in classes other than Dipeptidyl peptidase IV (DPP4) inhibitors.
Inclusion criteria: inclusion criteria:

 18 years of age or older

 Newly prescribed Saxagliptin or an OAD in a class other than DPP4 inhibitors

 Enrolled in the respective database for at least 180 days prior to the first prescription for Saxagliptin or other OAD in a class other than DPP4 inhibitors

Exclusion criteria: :

 Patients identified with a diagnostic code for any of the cardiovascular outcomes of interest within the 180-day baseline period

 Patients prescribed a DPP4 inhibitor during the baseline period


Hyperbaric Oxygen Therapy in Chronic Stable Brain Injury

Summary: The purpose of this study is to discover the feasibility of conducting clinical research in individuals with chronic sequelae following brain injury who are given hyperbaric oxygen. This study will also look at the outcome of individuals with a chronic stable brain injury due to trauma, anoxia (lack of oxygen to the brain), or stroke, who are given hyperbaric oxygen. Outcome measures testing cognitive (memory, etc.) and functional (balance, strength, etc.) measures will be performed before the hyperbaric sessions, immediately following them, and 6 months later. The subject will receive 60 hyperbaric sessions, 60 minutes in the chamber, to a pressure of 1.5 ATA, once daily, Monday through Friday.
Inclusion criteria: inclusion criteria:

 Subject has had a brain injury at least 12 months prior to study enrollment.

 Subject is at least 18 years old.

 Etiology of brain injury: Stroke, anoxia, and trauma

 Must be able to equalize ears, or have tympanostomy tubes

 Willingness to complete outcome measures and complies with the research protocols.

 Commitment to pay the hospital for hyperbaric oxygen.

Exclusion criteria: :

 Glasgow Coma Scores less than 13 at the time of hyperbaric oxygen evaluation.

 Poorly controlled seizures(ie:>1 generalized seizure in past 3 months despite appropriate anticonvulsant therapy). Pharmacologically-controlled seizures or focal seizures are not an exclusion to participate.

 Inability to participate in outcome assessments (eg: blindness, quadraplegia)

 Claustrophobia (unwillingness or inability to enter the hyperbaric chamber).

 Inability to equalize ears. The patient could elect to have bilateral tympanostomy tubes.

 Inability to protect airway, and or requiring frequent suctioning.

 Patients requiring tracheostomy will be ineligible due to limitations in autoinflation of the middle ear space and difficulty to perform airway suctioning in the single-person chamber.

 Pregnancy (beta HCG will be assayed in women who could be pregnant prior to enrollment).

 Severe psychiatric disorders such as schizophrenia and bi-polar disease. We appreciate that psychiatric problems such as depression and anxiety may follow brain injuries so we would not exclude patients based on brain-injury induced psychiatric disorders, but will exclude patients with severe pre-injury psychiatric disorders.

 Patients taking lithium (due to the possibility of concomitant toxic side effects with hyperbaric oxygen therapy, specifically hyperexcitability).

 Degenerative Mental Disease (eg: Alzheimer's, multiple sclerosis, senile dementia, severe psychiatric disorder (schizophrenia, bi-polar disease, etc.).

 Presence of chronic debilitating disease (end-stage renal disease, end-stage liver disease, diabetes with sequelae).

 Heart failure patients with ejection fractions less than 50% or inability to lay supine.

 Patients with active malignancy, or prior treatment with cisplatin or bleomycin (there is some evidence that prior cisplatin and bleomycin therapy may place the patient at increased risk for serious oxidated stress with inhalation of high concentrations of oxygen).

 Evidence of current recreational drug use, either by history, or by comprehensive urine drug testing (due to confounds on outcome measure interpretation).

 Consumption of more than the equivalent of 12 beers/week habitually.

 Prior treatment with hyperbaric oxygen for chronic brain injury within the last year.

 Women of child-bearing potential

['Brain Injury', 'Sequelae', 'Stroke', 'Anoxia', 'Trauma']

Brain Injury
Sequelae
Stroke
Anoxia
Trauma


Macrolides to Prevent Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease

Summary: The purpose of this study is to determine whether macrolide therapy is effective in treating patients hospitalized with asthma exacerbations or chronic obstructive pulmonary disease (COPD)exacerbations. We hypothesize that compared to placebo, maintenance therapy with macrolides, when added to usual care, a) improves respiratory symptoms, b) improves quality of life, c) reduces airway inflammation, d) reduces airflow obstruction, and e) decreases the rate of re-exacerbations.
Inclusion criteria: inclusion criteria:

 Physician-diagnosis of asthma, COPD exacerbation, or undifferentiated asthma/COPD exacerbation

 Admitted to the inpatient medical service at Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center

 Evidence of airflow obstruction on spirometry (FEV1/FVC<70%)

 Age 18 years or older

Exclusion criteria: :

 History of allergy or other contraindication to macrolides (azithromycin, erythromycin, clarithromycin)

 Treatment with any macrolide in the 4 weeks prior to study entry

 Elevated AST or ALT (2 or more times the upper limit of normal) on current admission

 Elevated alkaline phosphatase (>1.25 times the upper limit of normal) on current admission

 Elevated total serum bilirubin (more than upper limit of normal) on current admission

 Previous participation in this study

 Patients prescribed digoxin (azithromycin may increase digoxin levels)

 Patients prescribed warfarin (azithromycin may increase INR in patients on warfarin)

 Patients prescribed pimozide (azithromycin may increase risk of arrhythmias)

 Patient unable to provide consent (e.g., language difficulty or history of dementia)

 Patient to be discharged to a location other than home (e.g., other hospital, long-term care facility)

['Asthma', 'Chronic Obstructive Pulmonary Disease']

Asthma
Chronic Obstructive Pulmonary Disease


Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Summary: This is a multicenter, prospective, randomized, double-blind, placebo-controlled trial that will enroll 1028 patients with at least moderately severe COPD over a three year period and follow them at regular intervals for one year. The primary endpoint is time to first acute exacerbation. Secondary endpoints include rates and severity of COPD exacerbations, cardiovascular events, all-cause mortality, lung function, dyspnea, quality of life and metoprolol-related side effects.
Inclusion criteria: inclusion criteria:

 Male and female subjects, ≥ 40 and less than 85 years of age

 Clinical diagnosis of at least moderate COPD as defined by the Global Initiative for Obstructive Lung Disease (GOLD) criteria (53):

 Post bronchodilator FEV1/FVC < 70% (Forced expiratory volume in 1 second/ forced vital capacity),

 Post bronchodilator FEV1 < 80% predicted, with or without chronic symptoms (i.e., cough, sputum production).

 Cigarette consumption of 10 pack-years or more. Patients may or may not be active smokers.

 To enrich the population for patients who are more likely to have acute exacerbations (54), each subject must meet one or more of the following 4 conditions:

 Have a history of receiving a course of systemic corticosteroids and/or antibiotics for respiratory problems in the past year,

 Visiting an Emergency Department for a COPD exacerbation within the past year, or

 Being hospitalized for a COPD exacerbation within the past year

 Be using or be prescribed supplemental oxygen for 12 or more hours per day

 Willingness to make return visits and availability by telephone for duration of study.

Exclusion criteria: :

 A diagnosis of asthma established by each study investigator on the basis of the recent American Thoracic Society/European Respiratory Society and National Institute for Health and Care Excellence guidelines.

 The presence of a diagnosis other than COPD that results in the patient being either medically unstable, or having a predicted life expectancy < 2 years.

 Women who are at risk of becoming pregnant during the study (pre-menopausal) and who refuse to use acceptable birth control (hormone-based oral or barrier contraceptive) for the duration of the study.

 Current tachy or brady arrhythmias requiring treatment

 Presence of a pacemaker and/or internal cardioverter/defibrillator

 Patients with a history of second or third degree (complete) heart block, or sick sinus syndrome

 Baseline EKG revealing left bundle branch block, bifascicular block, ventricular tachyarrhythmia, atrial fibrillation, atrial flutter, supraventricular tachycardia (other than sinus tachycardia and multifocal atrial tachycardia), or heart block (2nd degree or complete)

 Resting heart rate less than 65 beats per minute, or sustained resting tachycardia defined as heart rate greater than 120 beats per minute.

 Resting systolic blood pressure of less than 100mm Hg.

 Subjects with absolute (Class 1) indications for beta-blocker treatment as defined by the combined American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Guidelines which include myocardial infarction, acute coronary syndrome, percutaneous coronary intervention or coronary artery bypass surgery within the prior 3 years and patients with known congestive heart failure defined as left ventricular ejection fraction <40%.(29, 30)

 Critical ischemia related to peripheral arterial disease.

 Other diseases that are known to be triggered by beta-blockers or beta-blocker withdrawal including myasthenia gravis, periodic hypokalemic paralysis, pheochromocytoma, and thyrotoxicosis

 Patients on other cardiac medications known to cause atrioventricular (AV) node conduction delays such as amiodarone, digoxin, and calcium channel blockers including verapamil and diltiazem as well as patients taking clonidine.

 Hospitalization for uncontrolled diabetes mellitus or hypoglycemia within the last 12 months.

 Patients with cirrhosis

 A clinical diagnosis of bronchiectasis defined as production of > one-half cup of purulent sputum/day.

 Patients otherwise meeting the inclusion criteria will not be enrolled until they are a minimum of four weeks from their most recent acute exacerbation (i.e., they will not have received a course of systemic corticosteroids, an increased dose of chronically administered systemic corticosteroids, and/or antibiotics for an acute exacerbation for a minimum of four weeks).

['Pulmonary Disease, Chronic Obstructive']


Five Versus Seven Day Antibiotic Course for the Treatment of Pneumonia in the Intensive Care Unit

Summary: The goal of the study is to determine if patients who are being treated for pneumonia in the intensive care unit can be safely treated with five days of antibiotics (the current standard is seven to eight days). The goal is to determine if the investigators can minimize antibiotic complications while still treating the infection. Patients in the study are randomly assigned to either receive antibiotics for a goal of five days or a goal of seven days. Every patient is followed daily, and if they are not responding to the antibiotics, the treating team in the intensive care unit care can continue the antibiotics for a longer course regardless of what group the patient is assigned. The investigator's hypothesis is that patients in the five day treatment goal will be able to receive less antibiotics than patients in the seven day treatment goal without any adverse effects.
Inclusion criteria: inclusion criteria:

 New diagnosis of pneumonia

 Patient in medical or surgical intensive care unit

 Age greater or equal than 18 years old

Exclusion criteria: :

 Neutropenia

 Recipient of a solid organ or bone marrow transplant

 Bacteremia

 Presence of Acinetobacter baumannii or Stenotrophomonas maltophilia from a respiratory tract culture

 Presence of a second infection requiring antibiotic therapy

 Pregnancy

 Enrollment in another clinical study

 Patient or surrogate unable to provide informed consent

 Attending intensive care unit physician declined enrollment in the study

['5 Days of Antibiotics', '7 Days of Antibiotics therapy for pneumonia']