Assessment of Pain Management in Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis Patients Who Are About to be Treated With Adalimumab

Summary: The purpose of this study is to assess whether or not adalimumab (Humira®) can influence pain medication in participants with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) with or without comorbidities, which do not constitute a contraindication for adalimumab as stated in the released summary of product characteristics. Therefore it shall be evaluated if pain medication which is used in these participants is changed, reduced or stopped due to adalimumab treatment.
Inclusion criteria: inclusion criteria:

 Patients aged ≥ 18 years for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

 Patients must fulfill international and national guidelines for the use of a biological disease modifying antirheumatic drug in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (chest x-ray and interferon gamma release assay or purified protein derivative-skin test negative for tuberculosis). In addition one of the following criteria must be fulfilled:

 unsatisfactory disease modifying antirheumatic drug response defined as failure to treatment with at least two disease modifying antirheumatic drugs including Methotrexate in patients with rheumatoid arthritis or psoriatic arthritis

 unsatisfactory non steroidal antiinflammatory drug response in patients with ankylosing spondylitis or unsatisfactory response to prior biological disease modifying antirheumatic drugs in patients with rheumatoid arthritis or psoriatic arthritis or ankylosing spondylitis

Exclusion criteria: :

 Patients who meet contraindications as outlined in the latest version of the Humira syringe® summary of product characteristics and Humira Pen® summary of product characteristics

 Patients participating in another study program or clinical trial

 Patients who have been treated with Humira before

['Rheumatoid Arthritis', 'Ankylosing Spondylitis', 'Psoriatic Arthritis']

Rheumatoid Arthritis
Ankylosing Spondylitis
Psoriatic Arthritis


Hyperspectral Imaging Pre and Post Endovascular Intervention

Summary: This trial will collect tissue oxygenation data via hyperspectral imaging before and after endovascular procedures.
Inclusion criteria: inclusion criteria:

 Patients with established diagnosis of lower limb ischemic based on their symptoms of claudication, rest pain, non-healing ulcers or gangrene and other vascular laboratory tests that are currently used to make this diagnosis and have been scheduled for endovascular revascularization.

 Age group between 50-85

 Gender - Male or Female

 Race - all race and ethnicities

Exclusion criteria: :

 Patients with known cardiac disease - new MI (within 3 months).

 Patients with hypertension with the systolic BP >200 or diastolic BP>110 on the day of testing

 Patients on supplemental O2 for chronic obstructive lung disease

 Bed-ridden subjects - either due to chronic disability or neurological problems

['Chronic Limb Ischemia', 'Non-Healing Ulcers']

Chronic Limb Ischemia
Non-Healing Ulcers


Patient Compliance to Self-collection for Detection of HPV-DNA

Summary: A study to investigate the compliance of unassisted women to self-collection of specimens for Hybrid Capture (HC) for detection of Human Papilloma Virus (HPV) DNA compared to Pap smear collection by medical personnel, as screening method to identify precursor lesions of cervical cancer.
Inclusion criteria: inclusion criteria:

 Women between 25-59 years-old

 Not pregnant

 Had held their last Pap smear for over a year

 Could read.

Exclusion criteria: :

 Women with previous hysterectomy

 History of cervical cancer or its precursors

 Bearers of some state of chronic immunosuppression (such as HIV ou autoimmune diseases)

 Those who underwent self-collection of their specimen during menstrual period


Exparel in Minimally Invasive Cardiac Surgery

Summary: The investigators are presently using Exparel, a slow released local anesthestic, in patients undergoing minimally invasive cardiac surgery. The primary objective of this study is to assess the efficacy of EXPAREL when delivered into the thoracotomy and chest tube sites to provide prolonged postoperative analgesia in patients undergoing minimally invasive cardiac surgery. Efficacy will be assessed by: the effectiveness of analgesia as measured by the subject's overall postoperative pain scores and postsurgical analgesic use.
Inclusion criteria: inclusion criteria:

 Patients aged 18-75 years inclusive and American Society of Anesthesiologists physical status 2-4.

 Undergoing minimally invasive cardiac surgery.

 Subjects must be physically and mentally able to participate in the study and complete all study assessments.

 Subjects must be able to give fully informed consent to participate in this study after demonstrating a good understanding of the risks and benefits of the proposed components of thoracotomy and chest tube sites infiltration.

Exclusion criteria: :

 History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics

 Any subject whose anatomy, or surgical procedure, in the opinion of the Investigator, might preclude the potential successful performance of a thoracotomy and chest tube sites infiltration.

 Any subject who in the opinion of the Investigator, might be harmed or be a poor candidate for participation in the study.

 Any subject, who in the opinion of the Investigator, is on chronic pain medicine, including large doses of nonsteroidal antiinflammatory drugs.

 Subjects who have received any investigational drug within 30 days prior to study drug administration, or planned administration of another investigational product or procedure during their participation in this study.


Reducing the Risk of Developing Major Depression in Adolescents/Young Adults With Minor Depression/Depression Symptoms

Summary: The purpose of this research study is to assess the feasibility of a combined primary care/web-based depression prevention intervention. Primary care physicians (PCP) currently lack an alternative behaviorally-based approach to antidepressant medications for individuals with depression symptoms or minor depression, but who have not yet developed Major Depression.~The objective of this study is to compare the feasibility and efficacy of motivational interviewing (MI) versus brief advice in primary care to engage adolescents with a web-based depression prevention intervention.
Inclusion criteria: inclusion criteria include:

 (1) age 14-18 years and

 (2) one risk factor for developing depression in the next two years: sub-clinical depressed mood (not meeting criteria of major depression),

 a family history of depression in a parent or sibling, or past personal history of depression or personal perception of risk depression and desire to participate

Exclusion criteria: :

 criteria include meeting criteria or undergoing active treatment for major depression (5 or more symptoms nearly every day with functional impairment, minor depression),

 bipolar disorder,

 panic disorder,

 conduct disorder,

 substance abuse or having suicidal ideation.

 Active treatment for depression is defined as receiving anti-depressant medication or counseling within one year of remission of symptoms from the most recent episode.

 Those who meet DSM-IV criteria for minor depression (3-4 symptoms) or who report significant functional impairment (very difficult or above on the Prime MD functional impairment scale) will be notified and offered a referral for an evaluation by a mental health specialist (and will be strongly encouraged to attend).

 Those with 1-2 symptoms of depression will also be offered evaluation and treatment from a mental health specialist. In each case, the primary care physician will be notified and the parents (if under the age of 19).

['motivational interviewing, brief advice in primary care']

motivational interviewing
brief advice in primary care


Study to See if Microcoil Insertion Reduces the Rate of Open Thoracotomy for Removal of Lung Nodules

Summary: LAY ABSTRACT~Statement of the health problem or issue: Of the estimated 24,000 Canadians who will be diagnosed with lung cancer in 2008, 21,000 will die of their disease. Based on this cancer incidence and survival data, the most promising current strategy for improving outcome is screening and early detection. It is suggested that if lesions are discovered at an earlier stage of disease, they will have a higher likelihood of being treatable and therefore, survival will be improved. CT detection of growing small lung nodules, many of which are non-cancerous (benign), raises the possibility of lung cancer and thus causes anxiety in patients and referring clinicians. Unfortunately, confident separation of benign from malignant small lung nodules cannot be reliably achieved using CT or PET criteria. Pathologic diagnosis using needle or excision biopsy is usually required.~Excision biopsy removes the entire nodule at one setting and eliminates the sampling error associated with needle biopsy, making it appealing to physicians and patients. To reduce post-operative pain and breathing difficulties, excision biopsy is often performed using minimally invasive surgery (video assisted thoracoscopic surgery, VATS). Finding small pulmonary nodules is often difficult with the minimally invasive camera (VATS) and a bigger incision (thoracotomy) is necessary in more than 60% of our patients.~We recently developed a technique of using platinum micro-coils, which are inserted in the lung nodule using CT guidance, to locate the nodule with fluoroscopy and then excise it with VATS. We have completed a pilot study (n=75 nodules; 69 patients) to determine the effectiveness of this technique. Seventy three (97%) 4-24-mm nodules were successfully removed at fluoroscopically guided VATS excision.~Objective of your project: To improve our ability to successfully excise small growing lung nodules with minimally invasive VATS surgery using CT guided micro-coil localization techniques.~How will you undertake your work? We propose to conduct a randomized controlled trial to determine if the use of CT guided platinum microcoil markers for VATS excision of subcentimetre pulmonary nodules can reduce the rate of conversion to open thoracotomy from 50% to 10%.~What is unique/innovative about your project? New image guided minimally invasive surgical technique for removing early growing cancers was developed at the Vancouver General Hospital and the University of British Columbia. This has been published in peer-reviewed journals and can potentially allow us to accurately locate and excise suspicious lung nodules~Relevance to Lung Association's mission statement? Lung cancer remains a major health problem in Canada. Early detection and screening programs allow for discovery of nodules when they are still very small and therefore, likely curable. Excision biopsy removes the entire nodule at one setting and eliminates the sampling error associated with needle biopsy, making it appealing to patients and physicians. To reduce post operative morbidity, costs and volume of lung removed, excision biopsy is often performed using video assisted thoracoscopic surgery (VATS) techniques. Using a pilot project grant from the BC Lung Association we have developed a new technique that allows preoperative CT marking of the nodule and minimally invasive removal of the lesion. We hope that this technique will allow earlier treatment of lung cancers and improve survival in this devastating disease.
Inclusion criteria: inclusion criteria: Patients will be evaluated for eligibility using the following criteria:

 All newly diagnosed patients with small lung nodules < 1cm that require excision with no history of prior ipsilateral thoracotomy.

 The nodules must be located in parts of the lung that are amenable to thoracoscopic wedge excision of the nodules.The external surface of the lesion must be at least 2 cm from the major pulmonary arteries, veins, and main bronchi to allow safe and adequate thoracoscopic excision of the lesion.

 Patients must be mentally competent to give written, informed consent

 Patients must be capable of independently completing standard English-language QOL instruments.

Exclusion criteria: :

 Patients will be excluded from the trial if they do not consent to participate in the study, or if the radiologist and surgeon agree that the nodule is located too centrally to be safely excised using thoracoscopic wedge techniques.

 Patients with more than three nodules will be excluded from the study.

 Patients with a positive diagnosis of non-small cell lung cancer obtained from sputum cytology, bronchoscopy, or CT guided needle biopsy will be excluded from the study.

 If the patient is excluded, he/she will receive the current standard treatment, which may include needle biopsy, continued observation of the nodule at three to six monthly intervals, or excisional surgery (thoracoscopy or open thoracotomy).


Safety in Seconds 2.0: An App to Increase Car Seat Use

Summary: This project will utilize the first web-based program to provide tailored injury prevention education. The existing Safety in Seconds program was adapted into a smartphone platform. Parents are recruited from and engage in the program in the clinical setting (PED or PTS). Parents download the app onto their smartphone which is used to ask the questions, collect a parent's responses, assess the parents' safety needs and give tailored directions for proper car sear use. The control group parents will also engage with the smartphone app and receive immediate feedback. However, they will receive tailored educational messages about smoke alarms. Parents will also have access to the online SIS v 2.0 Parent Portal which will have educational features (e.g., tips for keeping children content in their CSSs, links to helpful websites). The investigators will use emerging technology such as push notification and email to remind parents to visit the portal and have their child's car seat reassessed.~The investigators plan to conduct a cost benefit analysis of the program's expected financial benefit from the perspective of a third party payer of medical claims and an in-depth examination of program adoption and implementation using qualitative data collected from key informant interviews, direct observations of the clinic environments, and document review.
Inclusion criteria: inclusion criteria:

 Visiting the Pediatric Emergency Department (PED) at Johns Hopkins Hospital or Arkansas Children's Hospital

 Parent or guardian of child 4-7 years

 English speaking

 Have and Android or iPhone smartphone

 Drive with the child in a car at least once per week in a car that the parent owns, borrows or gets a ride round-trip

 Resident of Baltimore City, MD or Little Rock, AR and surrounding area.

Exclusion criteria: :

 PED has flagged case as suspected abuse

 Another household member is enrolled in the study

 In Arkansas, less than 18 years without parent present at the PED

['Parent Action Report', 'Parent Portal']


Study of Nimotuzumab in Combination With Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma

Summary: A higher percentage of radical resection is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone for esophageal cancer. And neoadjuvant chemotherapy may improve overall survival after surgical resection. Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). The concurrent trial is a clinical phase II trial designed to assess the efficacy of the combination of Nimotuzumab administered concurrently with neoadjuvant chemotherapy in patients with resectable Esophageal Squamous Cell Carcinoma, and to further investigate its side-effect and toxicity
Inclusion criteria: inclusion criteria:

 Histological or cytologic diagnosis of Esophageal squamous cell carcinoma

 ECOG performance status 0-2

 Age:18-70 years

 Joined the study voluntarily and signed informed consent form

 Patients must not have received any prior anticancer therapy

 Resectable disease, Stage IIA-IIIC, T2N0M0-T3N1M0（AJCC 2009）

 Target lesions can be measured according to RECIST criteria

 No serious system dysfunction and immuno-deficiency, Adequate organ function including the following: Hemoglobin ≥9 g/dL, WBC≥3x109/L, Neutrophils (ANC )≥1.5x109/L, platelet count ≥100x 109/L, TBIL<1.5 x ULN, ALT and AST ≦ 2.5 x ULN, creatinine ≦ 1.5 x ULN

 Use of an effective contraceptive for adults to prevent pregnancy

 Life expectancy of more than 3 months

Exclusion criteria: :

 Not suitable to surgery

 cervical Esophageal Carcinoma(distance of incisor tooth<19cm)

 early Esophageal Carcinoma(Stage I)

 complete esophageal obstruction，Esophageal perforation or hematemesis

 other malignant tumors, except for skin basal cell carcinoma, or cervical carcinoma in situ

 pregnant or breast-feeding women or people during the birth-period who refused to take contraceptives

 Uncontrolled seizures or psychiatric diseases, loss of control over their own behavior 11、 History of serious allergic or castor oil allergy 12、 Patients who are not suitable to participate in the trial according to researchers

['Nimotuzumab combined with paclitaxel and cisplatin']

['Esophageal Squamous Cell Carcinoma Resectable']


Effectiveness of Radial Extracorporeal Shockwave Therapy on Tennis Elbow

Summary: Background:~Tennis elbow, also known as lateral epicondylitis, is the inflammatory status of insertion site of common extensor tendon to humerus. It is usually related to overuse of local muscle. Radial extracorporeal shock wave therapy (rESWT) is a non-invasive physical treatment. It applies shockwave energy to the lesion site, enhancing the growth of microvascularity, inducing tissue repair, and thus relieving the symptom.~The purpose of this study is to understand the therapeutic effect of rESWT to tennis elbow.~Material and Methods~Subjects: 30 patients will be recruited from outpatient department of physical medicine and rehabilitation department.~Duration: 2013.09.01-2015.05.31~Methods: The patients will be randomly divided into the experimental group and the control group through the draw, with 15 patients in each group. Patients in the experimental group receive rESWT plus routine rehabilitation program. Patients in the control group receive sham shockwave therapy plus routine rehabilitation program.~Assessment: Before the therapy starts, patients who match the inclusion criteria will be evaluated using tools mentioned below:~General data: age, sex, body height, body weight, affected side, medical history~Assess upper extremity function and symptom with Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH)~Assess severity of pain with Visual Analogue Scale (VAS)~Assess grip strength with grip strength dynamometer~Measure the size of tear (if any) of common extensor tendon through ultrasonography, and assess the texture of common extensor tendon through real-time sonoelastography (RTS)~Patients will be followed up 6 weeks, 3months, and 6 months after therapy starts. They will be re-assessed of upper extremity function and symptom, severity of pain, grip strength, and presentation on ultrasonography and RTS.
Inclusion criteria: inclusion criteria:

 Aged > 18 years old

 Lateral elbow pain lasting > 3 months

 Pain induced by direct compression on the lateral epicondyle or common extensor tendon, resistant wrist extension and pronation in the elbow extension position, or static stretching of common extensor tendon through the palmer flexion in wrist pronation and elbow extension position

Exclusion criteria: :

 Generalized inflammatory arthritis (e.g., rheumatic arthritis)

 Pain at the proximal part of involved arm (e.g., shoulder pain, neck pain)

 Pain other than elbow pain at the involved arm

 Abnormal neurogenic symptom over the involved arm (e.g., radicular pain, hands numbness, hemiplegia)

 Wound or skin lesion at the elbow of the involved arm

 Pregnancy

 Severe local or systemic infection

 Malignancy

 Coagulopathy

 Cardiac pacemaker

 History of surgical treatment at the elbow of the involved arm

 Non-steroid anti-inflammatory drug (NSAID) use orally or topically at the elbow of the involved arm in the past week

 Local steroid injection at the elbow of the involved arm in the past 3 months

 Oral steroid use in the past 6 weeks

 Refusal to sign the informed consent

 Impairment in self-expression (e.g., dementia, aphasia)

 Inability/unwillingness to participate in all the measurements.

['Radial extracorporeal shock wave therapy (rESWT)', 'sham shockwave therapy', 'Physical therapy']

['Lateral Epicondylosis', 'Lateral Epicondylitis', 'Tennis Elbow']

Lateral Epicondylosis
Lateral Epicondylitis
Tennis Elbow


SBI in Children With d-IBS

Summary: IBS is the most common diagnosis in new patients in our pediatric gastroenterology clinic, accounting for 36 % of all new patients. Pediatric IBS patients always have a problem with defecation, characterized either as diarrhea predominant or constipation predominant. About one third of pediatric IBS subjects have d-IBS. There are no FDA approved treatments for children with d-IBS. There is evidence that diarrhea predominant irritable bowel syndrome d-IBS may be caused by a mild inflammation in the intestinal lining. Oral serum-derived bovine immunoglobulin protein isolate (SBI) is a medical food, believed to treat mild inflammation in the small intestine associated with some cases of d-IBS, especially those arising after acute gastroenteritis. It improved pain and diarrhea in adults with d-IBS. Our aim is to determine if SBI improves the number of spontaneous bowel movements in children with d-IBS.
Inclusion criteria: inclusion criteria:

 Males and non-pregnant females between 8 years and 18 years at the time of consent.

 Able to obtain parental or legal guardian informed consent from subjects as applicable.

 d-IBS determined by ROME III criteria. A Rome III diagnosis consists of recurrent abdominal pain or discomfort at least 2days/week in the last 3 months prior to enrollment associated with two or more of the following10:

 1. Improvement with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form (appearance) of stool.

Exclusion criteria: :

 Children taking pharmacologic treatment for d-IBS will be excluded.

 Children who are unable to articulate symptoms of IBS will be excluded.

 Non-English speaking children will be excluded.

 Children with known allergy or hypersensitivity to beef or any component of SBI.

 Pregnancy.


The Role of Viral Infection in Acute Exacerbations of Non-cystic Fibrosis Bronchiectasis in Adults

Summary: Bronchiectasis is clinically characterized by irreversible dilation of the bronchi and bronchioles leading to persistent cough, purulent sputum, and airway ﬂow limitation, which may be accompanied by recurrent exacerbations.It has been increasingly recognized that respiratory viruses are mainly responsible for acute exacerbation of chronic pulmonary diseases, i.e. asthma, chronic obstructive pulmonary disease and cystic fibrosis. However,little is known about the roles of viral infection in driving exacerbations of bronchiectasis.This study aims to identify the frequency of common viral infections and determine the roles that viruses play in acute exacerbations of bronchiectasis.
Inclusion criteria: inclusion criteria:

 Age ≥ 18 years

 HRCT-diagnosed Bronchiectasis

 Capable of providing written informed consent

Exclusion criteria: :

 Patient judged to have poor compliance

 Cystic fibrosis bronchiectasis


Stopping Postpartum Vitamin A Supplementation: Missing Concealed Benefit

Summary: The purpose of this study is to evaluate the effect of post-partum maternal vitamin A supplementation on breast milk bioactive compounds and immune status, growth and morbidity of children in the first four months of life.
Inclusion criteria: inclusion criteria:

 Pregnant women >-18 years of age with low-risk obstetric

Exclusion criteria: :

 Pregnant women expecting a multiple birth

 Take vitamin A supplements during postpartum apart from study intervention

 Premature birth

 Newborn babies with birth defects and / or other serious diseases

['Vitamin A (<3-day postpartum)', 'Vitamin A (6 wk postpartum)', 'Vitamin A (<3-day and 6 wk postpartum)', 'Placebo']

Vitamin A (<3-day postpartum)
Vitamin A (6 wk postpartum)
Vitamin A (<3-day and 6 wk postpartum)
Placebo


Screening and Identification of Human Urate Transporter hURAT1 MicroRNA

Summary: This study intends to use in patients with renal tissue and blood samples, screening and identification of renal tissue hURAT1 regulating the expression of micro-RNA, for further study of uric acid stone formation mechanism and the occurrence of clinical preventive uric acid stones provide new clues and new intervention targets.
Inclusion criteria: inclusion criteria:

 A、B group were enrolled standards: ① aged 18-65 years old; ② comply with percutaneous nephrolithotomy lithotripsy indications for surgery; ③ ECT tips ipsilateral normal or mildly impaired renal function.

 Group C patients were enrolled standards: ① aged 18-65 years old; ② normal renal function, not associated with urinary calculi in patients; ③ cancer patients met radical nephrectomy indications for surgery; ④ emergency trauma patients suffering from kidney resection surgical indications.

Exclusion criteria: :

 aged <18 years or> 65 years; ② neurological disease or cognitive dysfunction; ③ can not be corrected or uncorrected coagulopathy; ④ associated with diabetes, hypertension and other metabolic diseases; ⑤ accompanied by tuberculosis, hepatitis, HIV and other infectious diseases; ⑥ poor tolerance to anesthesia and surgery, such as: severe cardiopulmonary disease, coagulation disorders, etc.; ⑦ ultrasound, renal imaging examination revealed renal cortex was significantly thinner (renal cortical thickness <1.5cm), structural variation; ⑧ with severe systemic or urinary tract infection; ⑨ ECT tips ipsilateral renal function is severely impaired or solitary kidney.


Efficacy of Combining Pasireotide With Aspiration Sclerotherapy to Improve Volume Reduction of Hepatic Cysts

Summary: Liver cysts are fluid filled cavities located in the liver. They are present in 2-11% of the general population, typically not causing any symptoms or complications. However, in a small subset of patients complaints of pain, abdominal fullness and distension, dyspnea and nausea occur.~Currently, aspiration and sclerotherapy is a treatment of choice in symptomatic patients with a large dominant liver cyst. However, studies reported early fluid reaccumulation and relative high recurrence rates of cyst growth after aspiration sclerotherapy ultimately leading to re-interventions. In this respect, somatostatin analogues are promising agents known for its volume reducing effect in patients with polycystic liver disease.~In this study the investigators want to evaluate the effect of combining aspiration sclerotherapy with the multi-receptor binding, long-acting somatostatin analogue Pasireotide.~The investigators hypothesize that administrating pasireotide before and after aspiration sclerotherapy could prevent early fluid reaccumulation and thereby result in a greater reduction of cyst diameter. Moreover, the investigators expect a lower rate of cyst recurrence and subsequently lower need for re-interventions.
Inclusion criteria: inclusion criteria:

 All patients who are diagnosed with a dominant liver cyst with an indication for aspiration and sclerotherapy are suitable for inclusion in this study.

 In order to be eligible to participate in this study, a subject must meet all of the following criteria:

 Age 18 - 70 years

 Indication for aspiration and sclerotherapy

 Providing informed consent

Exclusion criteria: :

 A potential subject who meets any of the following criteria will be excluded from participation in this study

 ASPIRATION SCLEROTHERAPY RELATED

['Pasireotide LAR 60 mg', 'Aspiration sclerotherapy', 'Placebo']

Pasireotide LAR 60 mg
Aspiration sclerotherapy
Placebo


Valsartan/Hydrochlorothiazide Combination vs Amlodipine in Patients With Hypertension, Diabetes, and Albuminuria.

Summary: The purpose of this study is assess if treatment with valsartan and a diuretic, hydrochlorothiazide, has beneficial effects in people with high blood pressure, diabetes, and albuminuria (protein in the urine) compared with amlodipine. In particular, the study will assess whether the treatment will decrease the stiffness of the blood vessels.
Inclusion criteria: inclusion criteria:

 type 2 diabetes

 elevated blood pressure and pulse pressure

 albuminuria

Exclusion criteria: :

 Severe hypertension

 History of stroke, myocardial infarction, heart failure, chest pain, abnormal heart rhythm

 Liver, kidney (not caused by diabetes), or pancreas disease

 Type 1 diabetes or uncontrolled type 2 diabetes

 Allergy to certain medications used to treat high blood pressure

 Other protocol-defined inclusion/


Clinical and Radiological Results of Osteochondral Repair Using MaioRegen in Knee and Ankle Surgery

Summary: Osteochondral lesions in knee and ankle are injuries commonly seen in young patients. MaioRegen fleece is a cartilage substitute which can be used in circumscribed defects.~This prospective study follows patients treated with MaioRegen implants from pre-surgery until 24 months post-surgery.
Inclusion criteria: inclusion criteria:

 single osteochondral lesion in knee/ankle (2-4 sq cm)

Exclusion criteria: :

 multiple osteochondral lesions

 pre-existing injuries/arthropathies

['implantation of MaioRegen fleece into osteochondral lesion']

['Osteochondral Lesion of Talus', 'Degenerative Lesion of Articular Cartilage of Knee']


HR-lowering Efficacy and Respiratory Safety of Ivabradine in Patients With Obstructive Airway Disease

Summary: The purpose of this study is to investigate heart rate lowering efficacy and respiratory safety of ivabradine in patients with asthma and COPD.
Inclusion criteria: inclusion criteria:

 documented diagnosis of asthma or COPD in accordance with guidelines

 stable condition, defined as a disease without exacerbation for at least 1 month prior to study enrolment

 mean HR in holter ECG recording of ≥ 60 bpm

Exclusion criteria: :

 disease exacerbation in previous month

 inability to understand instructions on study procedures

['Asthma, Chronic Obstructive Pulmonary Disease (COPD)']


Role of Dairy Products in Weight Maintenance

Summary: The goal of the current study is to determine the role of dairy in similarly preventing weight and fat re-gain in obese adults who have successfully completed a weight loss diet program.240 obese subjects will undergo a meal-replacement-based weight loss plan designed to produce a 10 kg weight loss in 8-12 weeks. Upon achieving the weight loss goal, subjects will be randomly assigned to either a low-dairy or high-dairy eucaloric weight maintenance diet for two years. Macronutrient distribution will be maintained constant and set at approximately the U.S. average. Primary outcomes include changes in body weight, body fat and anatomical distribution of fat (via dual x-ray absorptiometry) and resting metabolic rate and substrate oxidation (via respiratory calorimetry); Secondary outcomes include blood pressure, circulating glucose, insulin, lipids and calcitrophic hormones. on prevention of weight regain in humans has not yet been assessed in clinical trials.
Inclusion criteria: inclusion criteria:

 Body mass index (BMI) 30-39.9 kg/m2

 Age 25-50 years

 No more than 3 kg weight loss during past three months

 Negative pregnancy test at entry; women of childbearing potential may be enrolled if they have had a tubal ligation or use one of the following means of contraception: condom, diaphragm, oral or implanted contraceptives, or intrauterine device. Women in exclusive relationships with male partners who have had a successful vasectomy will not be required to use any additional means of birth control.

Exclusion criteria: :

 BMI < 30 or >40

 Type II diabetes requiring the use of any oral antidiabetic agent and/or insulin (because of confounding effects on body weight regulation)

 Adverse response to study foods (lactose intolerance, dairy intolerance, dairy allergy); this will be determined by self-report.

 History or presence of significant metabolic disease which could impact on the results of the study (i.e. endocrine, hepatic, renal disease)

 History of eating disorder

 Presence of active gastrointestinal disorders such as malabsorption syndromes

 Pregnancy or lactation

 Use of obesity pharmacotherapeutic agents within the last 6 months

 Use of over-the-counter anti-obesity agents (e.g. those containing phenylpropanalamine, ephedrine and/or caffeine) within the last 6 months

 Recent (past 12 weeks) use of tobacco

 Recent (current or past 12 weeks) use of any psychotropic medication

 Recent (past four weeks) initiation of an exercise program

 Recent (past twelve weeks) initiation of hormone replacement therapy or change in HRT regimen

 Recent (past twelve weeks) initiation of hormonal birth control or change in hormonal birth control regimen


Intra-hepatic Artery Bone Marrow Derived Stem Cells Infusion for the Treatment of Advanced Liver Cirrhosis

Summary: Liver disease is a common medical problem in Saudi Arabia. Early studies indicated that around 10% of the Saudi population is either infected with hepatitis B or C. An estimated 12% of chronic HCV and HBV patients undergoing liver biopsy from Saudi centers have cirrhosis. Of these 3-5% would decompensate yearly thereby requiring liver transplantation. Based on the most recent national census figures, and a 1-2% prevalence rate of HBV and HCV nationwide, an estimated 1,000 patients would require liver transplantation on a yearly basis for decompensated cirrhosis.~Liver transplantation is the only available life saving treatment for patients with end stage liver disease. Unfortunately less than 100 liver transplantations are performed in Saudi Arabia in three centers. Around 100 other patients travel abroad for transplantation annually while all other patients progressively deteriorate and eventually die from the complications of decompensated liver cirrhosis.~In addition, even in patients who are listed for liver transplantation, often patients are too sick to wait on the transplant list that often takes more than a year and the on-list mortality is high. A procedure or an intervention that may help to stabilize liver function in order to help patients survive on the transplant list while awaiting liver transplantation would be of immense benefit. Examples of such interventions are already approved and used in some centers like the MARS system.
Inclusion criteria: inclusion criteria:

 Age >18 years

 Clinically diagnosed liver cirrhosis by any of the following: ultrasound/MRI/ CT/ + tissue biopsy.

 MELD score ≥ 18 and <35

 Ability to sign an informed consent

 Refused by liver transplant program or labeled as not a liver transplant candidate, decided by at least 3 transplant physicians

Exclusion criteria: :

 On a liver transplantation waiting list

 Questionable diagnosis of cirrhosis

 Prior history of organ transplantation

 Past history of malignancy within the 2 years prior to inclusion

 Probable or diagnosis of hepatocellular carcinoma

 Major hepatic vascular thrombosis (hepatic artery, or portal or hepatic veins)

 Serious cardiovascular or respiratory disease, or other medical condition with a high anticipated mortality within twelve months

 Current or recent (within the past 4 weeks) use of vasoactive drugs (Epinephrine, Norepinephrine, Vasopressin, Dopamine, terlipressin)

 Type-1 (acute) hepatorenal syndrome

 Levels of serum creatinine >150 µmol/ml and/or creatinine clearance <30 ml/min (as calculated by MDRD system)

 Documented or suspected ongoing infection

 Active or recent gastrointestinal bleeding episode (in the previous 4 weeks)

 Active alcohol abuse extending to within the previous six months

 Pulmonary hypertension (PAP > 35 mmHg), porto-pulmonary hypertension or hepatopulmonary syndrome

 Pregnancy

 HIV infection

 Active or past drug addiction within the preceding 6 months

 History of serious or uncontrolled psychiatric disease or depression

 Contraindications to the angiography procedures (e.g. arterial aneurysm, kinking, thrombosis)

 Contraindications for bone marrow biopsy (e.g. bleeding diathesis)

 Prior shunt operative shunt procedure


Cardiorenal Interactions During Treatment of Acute Decompensated Heart Failure: Diuretics Versus Ultrafiltration

Summary: The CRUF trial is a prospective randomized monocentric trial comparing different impact of diuretics versus ultrafiltration on renal congestion, plasma refill rate, echocardiographic filling pressures, neurohormonal activation and biomarkers of Acute Kidney Injury (AKI).
Inclusion criteria: inclusion criteria:

 >18 years old

 Severe systolic heart failure with ejection fraction <40%

 And Hospitalisation for decompensated heart failure

 And New York Heart Association (NYHA) III or IV

 And 1 of the following:

 Jugular vein distension>6cm

 Tissue Doppler mitral annulus lateral>12 or medial>15

 Chest X-ray: pulmonary edema or pleural effusion

Exclusion criteria: :

 Need for inotropic or vasopressive agents

 Use of intravenous (IV) contrast media

 Acute coronary syndrome

 Need of dialysis

 Severe co-morbidity

 Contra-indications for anticoagulation

 Pregnancy


A Comparitive Bioavailability Study of Metformin Hydrochloride Liquid 500mg/ 5 mL Under Fasting Conditions and After Low and High Fat Meal

Summary: To assess the food effect on pharmacokinetic profile of metformin liquid 100 mg/mL of Ranbaxy Laboratories in healthy, adult, human subjecis following a dose administration of 10 mL (1000 mg) under fasting conditions, after a Iow fat meal and after a high fat meal
Inclusion criteria: inclusion criteria:

 Be in the age range of 18.45 years.

 Be neither overweight nor underweight for his/her height as per the Life Insurance Corporation of India height/weight chart for non-medical cases.

 Have voluntarily given written informed consent to participate in this study.

 Be of normal health as determined by medical history and physical

 Examination of the subjects performed .within 28 days prior to the commencement of the study.

 If female and:

 Of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condoms, foams, jellies, diaphragm, intrauterine device (IUD), or abstinence; or

  Is postmenopausal for at least 1 year; or Is surgically sterile bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

Exclusion criteria: :

 History of allergy to metformin and other related antidiabetic biguanide preparations.

 Any evidence of organ dysfunction or any clinically significant deviation from the normal, in physical or clinical determinations.

 Presence of disease markers of HIV 1 and 2, Hepatitis B and C viruses and syphilis infection.

 Female volunteers demonstrating a positive pregnancy screen.

 Female volunteers who are currently breastfeeding.

 Presence of values' which are clinically significantly different from normal reference ranges for hemoglobin, total white blood cells count, differential WBC count and platelet count

 Positive for urinary screen testing of drugs of abuse (opiates and cannabinoids

 Presence of values which are significantly different from normal.reference ranges (as defined in Appendix 5) for se- rum creatinine, blood urea nitrogen serum aspartate aminotransferase (AST), serum alanine aminotranferase (ALT), serum alkaline phosphatase, serum billrubin, plasma glucose and serum cholesterol

 Clinically abnormal chemical and microscopic examination of urine defined as presence of RBC, WBC (>4/HPF), epithelial cells (>4/HPF), glucose, (positive) and protein (positive).

 History of serious gastrointestinal, hepatic, renal, cardiovascular, pulmonary, neurological or hematological disease, diabetes or glaucoma.

 History of any psychiatric illness. which may impair the ability to provide written informed consent.

 Regular smokers who smoke more than 10 cigarettes daily or have difficulty abstaining from smoking for the duration of each study period.

 History of drug dependence or excessive alcohol intake on a habitual basis of more than 2 units of alcoholic beverages per day (1 'unit equivalent to half pint of beer or 1 glass of wine or 1 measure of spirit) or have difficulty in abstaining for the duration of each study period.

 Use of any enzyme modifying drugs within 30 days prior to Day I of this study


Acute Gastrointestinal Tolerability Following a Single Serving of a Novel Dietary Fiber

Summary: The study will assess the gastrointestinal tolerability of a single serving of a novel dietary fiber at three different dose levels in generally healthy men and women. Double-blind controlled, cross-over clinical trial with negative (no added fiber) and positive controls. Single dose, with 24 hours data collection and 1 week wash-out between cross-overs. 45 randomized, generally healthy men and women, 18-54 y, BMI higher or equal to 18.5 and smaller or equal to 39.99 kg/m2. Novel dietary fiber ingredient and positive control will be delivered in 240 ml beverages.
Inclusion criteria: inclusion criteria:

 Subject is male or female, 18-54 years of age, inclusive.

 Subject has a body mass index (BMI) ≥18.50 and ≤39.99 kg/m2 at visit 1 (day -7) and has been weight stable (± 4.5 kg) for the previous 3 months.

 Subject is judged to be in good health on the basis of medical history.

 Subject is willing to maintain his or her habitual diet and physical activity patterns, including habitual use of study approved medications and/or dietary supplements throughout the study period.

 Subject is willing to avoid foods/beverages that cause GI-distress, as well as high-fiber foods for 24 h prior to, and following, visits 2, 4, 6, 8, and 10.

 Subject understands the study procedures and signs forms providing informed consent to participate in the study and authorization for release of relevant protected health information to the study Investigators.

Exclusion criteria: :

 Subject reports any clinically important GI condition that would potentially interfere with the evaluation of the study product (e.g., inflammatory bowel disease, irritable bowel syndrome, history of surgery for weight loss, gastroparesis, and clinically important lactose intolerance).

 History or presence of clinically important endocrine (including type 1 or 2 diabetes mellitus), cardiovascular, pulmonary, biliary, renal, hepatic, pancreatic, or neurologic disorders that, in the opinion of the Investigator, could interfere with the interpretation of the study results.

 Recent history (within 6 weeks of screening, visit 1) of constipation (defined as <3 bowel movements per week), and/or diarrhea (defined as ≥3 loose or liquid stools/d).

 Recent (within 6 weeks of screening, visit 1) episode of acute GI illness such as nausea, vomiting or diarrhea.

 Daily use of non-steroidal anti-inflammatory drugs (NSAIDS).

 Daily use of antacids, proton pump inhibitors, H2 blockers.

 Recent use of antibiotics (within 3 months of visit 2, day 0).

 Use of medications (over-the-counter and prescription) or dietary supplements (within 3 weeks of visit 2, day 0) known to influence GI function such as constipation medications and supplements (including laxatives, enemas, fiber supplements and/or suppositories); anti-diarrheal agents; anti-spasmodic; prebiotic and probiotic supplements.

 Extreme dietary habits, including but not limited to vegetarian diets and intentional consumption of a high fiber diet.

 Known allergy or sensitivity to food ingredients such as: soy, dairy (milk), wheat, egg, peanuts, tree nuts, fin fish and crustacean.

 Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg at visit 1, day -7). One re-test will be allowed on a separate day prior to visit 2 (day 0), for subjects whose blood pressure exceeds either of these cut points at visit 1, in the judgment of the Investigator.

 History of cancer in the prior two years, except for non-melanoma skin cancer.

 Any major trauma or surgical event within 2 months of visit 2, day 0.

 Females who are pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential who are unwilling to commit to use of a medically approved form of contraception throughout the study period. The method of birth control must be recorded in the source documentation.

 Exposure to any non-registered drug product within 30 days prior to the screening visit.

 Recent history of (within 12 months of visit 1) or strong potential for alcohol or substance abuse. Alcohol abuse defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1½ oz distilled spirits).

 Recent history of (within 2 months of visit 1) use of any tobacco-containing products.

 Individual has a condition the Investigator believes would interfere with his or her ability to provide informed consent, comply with the study protocol, or confound the interpretation of the study results or put the subject at undue risk.

['Novel Fiber', 'Positive Fiber control', 'Negative Control']

Novel Fiber
Positive Fiber control
Negative Control


Effectiveness and Acceptability of Internet-delivered Treatment for Depression, Anxiety and Stress

Summary: The aims of this study are to test the effectiveness and acceptability of internet-delivered treatment for depression, anxiety and stress in university students. These data will inform the methods for a future randomized controlled trial.~The trial will establish an initial estimate of the effectiveness of these online interventions for students in terms of within-group effect sizes associated with changes in depression, anxiety and stress from pre to post-intervention and follow-up. These data will be used to estimate the sample size for a future trial to ensure that the study is sufficiently powered. A conservative estimate using the 90% upper confidence limit will be used to inform the sample size calculation of the definitive RCT.~Acceptability of the intervention to participants will be assessed using data on usage and engagement with the intervention (e.g. percentage of participants completing each module, average number of log ins, average time spent per session and total time spent on the program). These data are acquired through the online SilverCloud system. Satisfaction with will be assessed through the use of a post-intervention questionnaire on satisfaction with accessing and using an online delivery format for treatment.
Inclusion criteria: inclusion criteria:

 Participants must be at least 18 years of age. Participants must have self-reported mild to severe symptoms of depression (5-27+) according to PHQ-9, self-reported mild to severe symptoms of anxiety (5-21+) according to GAD-7, or self-reported mild to severe symptoms of stress (15-34+) according to the stress sub-scale of DASS-21.

Exclusion criteria: :

 Students who currently are in face-to-face therapy at UCCS or BHS will be excluded. Students who score in the red zone in terms of risk of self-harm on the screening questions routinely used at UCCS will not be referred to the study. Students who score greater than 0 on the PHQ-9 self-harm item during the initial screening phase will be automatically directed to be further evaluated and alerted that a counselor will try to reach them. Based on this further evaluation, they may be recommended to seek help from their health/counseling service and may/may not be eligible to participate in the study. They will be telephoned within 1 working day and contacted by email if they cannot be reached by phone.

['Space from Depression', 'Space from Anxiety', 'Space from Stress']

Space from Depression
Space from Anxiety
Space from Stress


Complete Lymph Node Dissection vs Watchful Waiting in Patients With Malignant Melanoma (Thickness of 1,0mm+ and Evidence of Metastases in the Sentinel Node)

Summary: Sentinel lymph node biopsy (SLNB) is considered as standard diagnostic procedure in melanoma patients carrying a reasonable risk for metastases. In numerous studies the prognostic role of micro metastases in the sentinel node (SN) was described. However, the prognostic value of a complete lymph node dissection in patients with a positive SN is still unclear.~This study was planned to analyse the survival outcome of patients with a positive SN receiving complete lymphadenectomy versus watchful waiting.
Inclusion criteria: inclusion criteria:

 Cutaneous melanoma with a tumour thickness of at least 1,00mm

 Positive sentinel node with micro metastases of max. 2mm in diameter

Exclusion criteria: :

 Mucosal or ocular melanoma

 Cutaneous melanoma located in the head/neck region

 Evidence of satellite, in transit or local metastases / recurrences

 Macro metastases of the SN or micro metastases of >2mm in diameter

 Additional immune-suppressive therapy

 Pregnant of lactating women

['Completion Lymphadenectomy', 'Clinical Monitoring (Palpation and node ultrasound)']


Intravenous Isosorbide Dinitrate Versus Sublingual Isosorbide Dinitrate for the Relief of Acute Anginal Episodes in Acute Coronary Syndrome (ACS) Patients

Summary: This is a randomized, double blind, placebo-controlled study, clinical trail designed to evaluate the efficacy safety and superiority of intravenous boluses of isosorbide dinitrate for the relief of acute anginal pain episodes in acute coronary syndrome patients in comparison with the usual manner of S/L isosorbide dinitrate .
Inclusion criteria: inclusion criteria:

 Age > 18 years or older.

 Admission to the ICCU with ACS (non-ST elevation acute coronary syndrome or 24 hours after ST elevation myocardial infarction) .

 Presence of ischemic symptoms (≥5 minutes) during hospitalization.

 Pain assessment of 3 out of 10 on Visual Analog Scale (VAS) 1 or dynamic ECG findings (ST segment deviation ≥0.05 mV or T wave inversion ≥ 0.3 mV)

 Willing and able to provide written informed consent according to the regulations of the Ministry of Health and the Helsinki committee instructions.

 -

Exclusion criteria: :

 Patient who meet any of the following criteria are excluded from the study:

 Persistent ST-segment elevation ≥ 1 mV in 2 or more contiguous leads or new LBBB.

 Acute pulmonary edema

 Sepsis

 Sustained systolic blood pressure < 90 mm Hg or evidence of cardiogenic shock

 Pregnant women

 Use at randomization of agents known to enhance the efficacy of nitrates.

 Clinically significant aortic stenosis

 Cr > 2 mg/dL

 Participation in another trial of an investigational drug or device on randomization.

 Allergy or sensitivity to nitatrate compounds

 Acute episode of cerebrovascular attack

 Inability to comply with the protocol and follow-up

 -

['iso sorbide dinitrate iv bolus or s/l']

['Unstable Angina', 'Myocardial Infarction']


Block-replacement Therapy During Radioiodine Therapy

Summary: Background: The use of radioactive iodine (131I) therapy as the definite cure of hyperthyroidism is widespread. According to a survey on the management of Graves' disease, thirty per cent of physicians prefer to render their patients euthyroid by antithyroid drugs (ATD) prior to 131I therapy. This strategy is presumably chosen to avoid 131I induced 'thyroid storm', which, however, is rarely encountered. Several studies have consistently shown that patients who are treated with ATD prior to 131I therapy have an increased risk of treatment failure. Mostly, patients with Graves' disease have been studied, while other studies were addressed also toxic nodular goiter. Thus, it is generally accepted that ATD have 'radioprotective' properties, although this view is almost exclusively based on retrospective data and is still under debate. Indeed, this dogma was recently challenged by two randomized trials in Graves' disease, none of which showed such an adverse effect of methimazole pretreatment. It cannot be excluded that the earlier results may have been under influence of selection bias, a source of error almost unavoidable in retrospective studies. Whether ATD is radioprotective also when used in the post 131I period has also been debated. In the early period 131I therapy following a transient rise in the thyroid hormones is seen which may give rise to discomfort in some patients. The continuous use of ATD during 131I therapy, possibly in combination with levothyroxine (BRT: block-replacement therapy), leads to more stable levels of the thyroid hormones. By resuming ATD following 131I therapy, euthyroidism can usually be maintained until the destructive effect of 131I ensues. Nevertheless, many physicians prefer not to resume ATD, probably due to reports supporting that such a strategy reduces the cure rate. Parallel to the issue of ATD pretreatment, the evidence is based on retrospective studies and the ideal set-up should be reconsidered. To underscore the importance of performing randomized trials we showed recently that resumption of methimazole seven days after 131I therapy had no influence on the final outcome.~Aim:To clarify by a randomized trial whether BRT during radioiodine therapy of hyperthyroid patients influences the final outcome of this therapy, in a comparison with a regime in which methimazole as mono-therapy is discontinued 8 days before radioiodine.~Patients and Methods: Consecutive patients suffering from recurrent Graves' disease (n=50) or a toxic nodular goiter (n=50) are included. All patients are rendered euthyroid by methimazole (MMI) and randomized either to stop MMI eight days before 131I or to be set on BRT. This latter medication continues until three months after 131I. Calculation of the 131I activity (max. 600 MBq) includes an assessment of the 131I half-life and the thyroid volume. Patients are followed for one year with close monitoring of the thyroid function.
Inclusion criteria: inclusion criteria:

 Hyperthyroid patients going to be treated with radioiodine either due to recurrent Graves' disease or toxic nodular goiter.

Exclusion criteria: :

 Age < 18 yrs.

 Allergy to anti-thyroid drugs

 Substernal or large (> 100ml) goiter

 Severe endocrine ophthalmopathy

 Pregnancy or lactation

 Suspicion of thyroid malignancy

 Unsafe contra-conception

 Physical or mental condition that hinders corporation

['Toxic Nodular Goitre', "Graves' Disease"]


Effect of Amlodipine on Anti-platelet Drug Effect in Patients With Coronary Artery Disease

Summary: Clopidogrel can reduce risk of cardiovascular disease by inhibiting platelet aggregation. It is metabolized to an active drug by a liver enzyme. Its efficacy may be measured by blood sampling for platelet activity, analyzed by VerifyNow device. Calcium Channel blocker (CCB) is also commonly used for blood pressure and anginal control in these patients. Dihydropyridine group of calcium channel blocker (e.g. amlodipine) inhibits this enzyme. There are observational studies reporting dihydropyridine CCB reducing clopidogrel effect, but the clinical implication is unclear.~This study test the hypothesis that there is no significant effect of dihydropyridines CCB on clopidogrel response compared with control. After giving consent, patients with suboptimal blood pressure or anginal control will be randomized to receive either dihydropyridine CCB or non-CCB as placebo. These patient will be follow-up in 1 month.
Inclusion criteria: inclusion criteria:

 ischemic heart disease patient, and

 given loading or maintenance dose of clopidogrel and in need of it for 1 or more month

 and in need of additional drug for optimal BP control (aim blood pressure <130/90) or angina control.

Exclusion criteria: :

 existing use of amlodipine

 thrombocytopenia

 end stage renal failure

 allergy to clopidogrel/ amlodipine

 pregnancy/ lactation

 strong inhibitor or inducer of cytochrome P450 3A4 enzyme within 7 days before start of the study.


Laparoscopic or Conventional Mesh Repair of Incisional and Umbilical Hernia

Summary: The aim of this study is to compare immediate and long-term (24 months) results of laparoscopic and open mesh repair of incisional and umbilical hernia.
Inclusion criteria: inclusion criteria:

 Age > 18

 Incisional or umbilical hernia over 2 cm and less than 6 cm in diameter

Exclusion criteria: :

 Patients with a complicated incisional (pain, occlusion, cutaneous necrosis), irreductible painless incisional or umbilical hernia will not be considered as a complication

 Patients with a recurrence of incisional hernia

 Patients with an incisional or umbilical hernia whose lateral edges are located so that fixation of the mesh (which must extend beyond the 4 to 5 cm) is not possible

 Pregnant women

 Patients with HIV therapy

 Patients with cirrhotic ascites or other signs of hepatic insufficiency (bilirubin> 35 micromol / l; TP < 55%) or significant thrombocytopenia (< 60 000 platelets)

 Patients with a contra indication for laparoscopy

 Patients with a life expectancy < one year, or whose mobility within two years of treatment will damage proper monitoring

 Patients unable to understand information about the protocol

['Laparoscopic mesh hernia repair', 'Open anterior approach']

Laparoscopic mesh hernia repair
Open anterior approach

['Incisional Hernia', 'Umbilical Hernia']


Study to Evaluate the Pharmacokinetic Profile of Salbutamol Delivered by Unit Dose Dry Powder Inhaler (UD-DPI) Compared to the Diskus and Metered Dose Inhaler (MDI) in Healthy Volunteers.

Summary: This is an open-label, two part, six period- cross over, randomised, single dose, single centre study in healthy subjects. This is the first clinical study for the UD-DPI. This study is divided into two parts. Part A will ascertain whether the pharmacokinetic (PK) of salbutamol delivered via the UD-DPI is comparable to the salbutamol delivered via the Diskus or MDI. For this reason four treatment doses consisting of three dose strength and two percentage blends will be assessed in Part A delivered via UD-DPI. Part A will also provide preliminary PK variability estimates to allow for better sample size/precision calculations for Part B. Part B will explore whether the UD-DPI has a pharmacokinetic exposure profile that is comparable to either Diskus or MDI in the presence of the charcoal block.
Inclusion criteria: inclusion criteria

 Male/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

 Body weight >=50 kg and body mass index within the range 19.0 - 34.0 kilogram per square meter (inclusive).

 A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records; or postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli-international units per milliliter (MlU/mL) and estradiol < 40 picograms per milliliter (pg/mL) (<147 picomole per liter) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in listed in protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method; Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotropin (hCG) test at screening or urine hCG prior to dosing AND; Agrees to use one of the contraception methods listed in protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until follow-up; OR has only same-sex partners, when this is her preferred and usual lifestyle.

 Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

 Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria: , outside the reference range for the population being studied may be included only if the Investigator agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

 Alanine transaminase, alkaline phosphatase and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

 Based on single or averaged corrected QT interval (QTc) values of triplicate ECGs obtained over a brief recording period: QTcF <450 milliseconds.

 Current non-smokers who have not used any tobacco- containing products within 3 months of screening and with a total pack year history of <=10 pack years [number of pack years = (number of cigarettes per day / 20) x number of years smoked].

 Able to use all medical device products included in the study adequately after training

 Part B

 Able to tolerate the charcoal block at screening

['Salbutamol Sulphate 150mcg UD-DPI Blister(1.6% blend)', 'Salbutamol Sulphate 200mcg UD-DPI Blister(1.6% blend)', 'Salbutamol Sulphate 250mcg UD-DPI Blister(1.6% blend)', 'Salbutamol Sulphate 200mcg UD-DPI Blister(1% blend)', 'Salbutamol Diskus 200mcg Blister', 'Salbutamol MDI 100mcg', 'Salbutamol Sulphate UD-DPI Blister (selected from Part A)', 'Salbutamol Sulphate 250mcg UD-DPI Blister (selected from Part A)', 'Salbutamol Diskus 200mcg Blister without activated charcoal', 'Salbutamol Diskus 200mcg Blister with activated charcoal', 'Salbutamol MDI 100mcg without activated charcoal', 'Salbutamol MDI 100mcg with activated charcoal']


The Interaction Between Calcium and Vitamin D Intake

Summary: We will study the relative importance of high calcium intake and vitamin D supplementation for calcium homeostasis, as determined by serum parathyroid hormone (PTH) and biochemical bone markers. We also intend to examine the interaction of vitamin D and calcium intake on calcium homeostasis. We hypothesize that optimal calcium supplementation and optimal vitamin D supplementation will lead to lower serum levels of PTH and markers of bone resorption compared with the placebo. We also theorize that when taken together, optimal calcium supplementation and optimal vitamin D intake will result in lower serum levels of PTH and bone markers compared with calcium or vitamin D taken alone.
Inclusion criteria: inclusion criteria:

 Healthy women aged 45 and above who have been menopausal at least 1 year (absence of menstrual period for a period of 12 months or more)

Exclusion criteria: :

 Any chronic medical illness including uncontrolled diabetes mellitus, recent history of myocardial infarction, or heart failure, malignancy, uncontrolled hypertension, obesity (BMI>35 kg/m2), history of anemia, leukemia, or other hematologic abnormalities, lupus, rheumatoid arthritis, or other rheumatologic disease, or kidney disease of any kind as determined by history and physical examination.

 Subjects with osteoporosis of the hip (total hip T-score equal or less than -2.5) or taking medications for osteoporosis such as bisphosphonates will be excluded.

 Pregnancy.

 Use of medication that influences bone metabolism (i.e. anticonvulsant medications, chronic use of steroids and high dose diuretics).

 Significant deviation from normal in medical history, physical examination, or laboratory tests as evaluated by the primary investigator.

 Patients with a history of hypercalciuria, hypercalcemia, nephrolithiasis, and active sarcoidosis will also be excluded.

 Participation in another investigational trial in the past 30 days prior to the screening evaluation.

 Unexplained weight loss of >15% during the previous year or history of anorexia nervosa.

 Medications that interfere with vitamin D metabolism.

 Patients with a habitual dietary calcium intake that exceeds 800 mg/day.

 Smokers greater than 1 pack per day will be excluded.

 Patients reporting alcohol intake greater than 2 drinks daily.

 Serum 25-hydroxyvitamin D level > 75 nmol/L.

['Calcium and vitamin D supplementation']


Importance of Peritoneal Free Fluid Cultures in Acute Appendicitis

Summary: The purpose of this study is to evaluate the frequency of positive free fluid cultures in both perforated and non-perforated appendicitis. In addition predictors of positive free fluid cultures will be analyzed.
Inclusion criteria: inclusion criteria:

 Appendicitis (Perforated/ Non-perforated) Free fluid Age: 6 - 90y

Exclusion criteria: :

 Immunosuppression (recent chemotherapy, chronic use of immunosuppressive medication) Age < 6 and > 90y


Characteristics of Idiopathic Familial Voice Disorders

Summary: The purpose the study is to determine the genetic causes of specific voice disorders that run in families. Researchers are particularly interested in two conditions;~Spasmodic dysphonia~Vocal fold paralysis~Familial vocal fold paralysis can be a life-threatening disorder that can cause difficulty with vocal fold movement for breathing and voice and sometimes for swallowing. Studies are ongoing at the NIH to better understand the pathophysiology and to relate it to the genetic pattern of inheritance. Families are being recruited to participate in these studies and are being provided with further information on the disorder and genetic counseling if desired. Physician referral is requested for affected members of families with vocal fold paralysis of an unknown cause occurring over at least 2 generations. All travel, lodging, examination and counseling costs are covered for both affected and unaffected members of a family. Examinations include: voice, laryngeal, neurological, electrodiagnostic testing, genetic counseling, and radiological studies....
Inclusion criteria: inclusion criteria:

 Symptoms present during speech and not apparent at rest,

 Symptoms less evident during whisper, singing or falsetto.

 Symptoms become worse with prolonged speaking, practice or anxiety.

 Reflexive and emotional aspects of voice function are unaffected, such as coughing, laughter or crying.

Exclusion criteria: :

 Any patient with a history of airway obstruction will be excluded from the study.

 Structural abnormalities affecting the larynx such as vocal fold nodules, polyps, carcinoma, cysts, contact ulcers, or inflammation (laryngitis).

 Reduction in vocal fold movement range during non-speech tasks such as whistling which would suggest either paralysis or paresis, joint abnormality or neoplasm.

 No smokers or tobacco users will be included in the study.

 Subjects with history of a psychiatric disorder, under the care of a psychiatrist, or on medications for treatment of a psychiatric disorder will be excluded from the study. Examples of psychiatric disorders to be excluded are: somatoform disorders, conversion disorders, currently under treatment for a major depression, or a history of schizophrenia or a bipolar disorder. However, a history of a previous episode of a minor reactive depression would not exclude a person from participation.

['Laryngeal Disease', 'Spastic Dysphonia', 'Voice Disorder']

Laryngeal Disease
Spastic Dysphonia
Voice Disorder


Study Evaluating the Cost of the Treatments of the Refractory Psoriatic Arthritis to the Conventional Therapy

Summary: The purpose of this study is to conduct an economic analysis on the cost of conventional therapy as compared to biologic therapy and the direct/indirect costs of disease management in patients with refractory psoriatic arthritis (PsA). Primary outcomes are to qualify the economic burden of refractory PsA care. The secondary outcomes are to assess efficacy, safety, and cost effectiveness of different therapies.
Inclusion criteria: inclusion criteria:

 Eighteen years of age or older

 Inflammatory arthropathy associated with psoriasis meet the ACR criteria for PsA

 Patients with diagnosis of active and progressive PsA who have failure with conventional treatments

Exclusion criteria: :

 Significant concurrent medical diseases including cancer or a history of cancer, uncontrolled congestive heart failure, myocardial infarctions within 12 months or other clinically significant cardiovascular diseases, immunodeficiency syndromes or concomitant infectious diseases.


BNP Testing in Patients With SOB on Presentation to ED

Summary: A trial to examine whether a new heart failure blood test can improve the outcome of patients presenting to the Emergency Department with shortness of breath.~We hypothesise that a BNP test performed in real-time in patients presenting to the Emergency Department with shortness of breath will help identify additional patients with CHF and consequently to change practice and allow more patients to recieve correct treatment earlier.
Inclusion criteria: inclusion criteria:

 We plan to include all patients presenting to the ED with shortness of breath that are over 40 years old and present with an emergency department triage category of 3 or higher.

Exclusion criteria: :

 Patients presenting with a traumatic cause of dyspnea, patients with severe renal disease (serum creatinine level of more than 250 micro mmol/L, patients with cardiogenic shock, and patients who have an early transfer to another hospital (within 24 hrs) will be excluded.


A Study of FK199B to Compare Efficacy With Zolpidem by Polysomnography in Patients With Insomnia

Summary: This study is to investigate the efficacy and safety of FK199B (Zolpidem MR Tablet) by polysomnography in patients with insomnia, excluding patients with schizophrenia or manic-depressive psychosis.
Inclusion criteria: inclusion criteria:

 Patient is diagnosed as a primary insomnia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)

 Patients complaining of insomnia continuously for 4 weeks or longer

 Patient's usual bedtime is between 9 p.m. and 12 a.m. for the 4 week period prior to initial screening

 Patient on most occasions sleeps for a total of ≥3 and <6.5 hours over the 4 week period prior to initial screening

 Patient's usual wake time after sleep onset in a single night is ≥45 minutes per night for the 4 week period prior to initial screening

 Patients have a body weight of ≥45 kg and ≤85 kg, a BMI of ≥18.5 and <30

Exclusion criteria: :

 Patients with schizophrenia or manic-depressive psychosis

 Patients with insomnia caused by physical diseases including chronic obstructive pulmonary disease, bronchial asthma, fibrositis syndrome, chronic fatigue syndrome, rheumatic disease, climacteric disturbance, and dermatitis atopic

 Patients with circadian rhythm sleep disorder

 Patient works night shifts

 Patients with alcoholic sleep disorder

 Patients with alcohol or drug dependence or a history of these

 Patients with insomnia related with drugs including antiparkinson, antihypertensive, or steroid drugs

 Patients with sleep apnea syndrome

 Patients with restless legs syndrome or periodic limb movement disorder

 Patients with epileptic insomnia

 Patients smoke on average 40 or more cigarettes a day

 Patients who had received psychotropic drugs other than hypnotics (including anxiolytic or antidepressant drugs for hypnotic effect) within a 4 week period prior to the initial screening

['Sleep Initiation and Maintenance Disorders']


The STOP CLOT Pilot Study: Study of Low Molecular Weight Heparin in High Risk Cesarean Section

Summary: Venous thromboembolism (VTE) remains the most common cause of maternal death in the developed world. VTE includes two conditions, deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT refers to a blood clot that has formed in a deep vein, often in the legs and/or pelvis and PE refers to the passage of these clots into the lungs (which can be fatal). VTE is up to 10 times more common in pregnant women than non-pregnant women of comparable age. More than a third of pregnancy related VTE occur during the 6 weeks after delivery. When compared with vaginal delivery, cesarean delivery further increases the risk of pregnancy associated VTE by three-fold.~A medication called low molecular weight heparin is sometimes prescribed during pregnancy and after delivery to prevent VTE. However, clinical practice varies because there hasn't been adequate research to determine that this medication is safe and effective at preventing VTE during this time. The potential benefits of the medication must also be weighed against its cost and possible side effects.~The researchers are conducting a study that will assess the effectiveness and safety of low molecular weight heparin in women who are at moderate to high risk of VTE after a cesarean section. They will monitor these women to determine if those who received the medication have fewer blood clots. Participants will also be monitored closely for any side effects.
Inclusion criteria: inclusion criteria (must meet inclusion criteria 1, 2 and 3):

 At high risk for thromboembolism (any one of the following):

 Age > 35 years

 Obesity (> 80 kg)

 Para 4

 Gross varicose veins

 Current infection

 Pre-eclampsia

 Immobility prior to surgery (> 4 days)

 Major current disease: includes heart or lung disease, cancer, inflammatory bowel disease, and nephrotic syndrome.

 Emergency cesarean section in labour

 Extended major pelvic or abdominal surgery (e.g. cesarean hysterectomy)

 Patients with a family history of VTE

 History of superficial phlebitis

 Delivered by cesarean section (emergency or planned)

 Signed, informed consent

Exclusion criteria:  (must not meet any of the following criteria):

 Greater than 36 hours since delivery

 Need for anticoagulation, including:

 Women with a confirmed thrombophilia

 Women with paralysis of lower limbs

 Women with personal history of VTE

 Women with antiphospholipid antibody syndrome (APLA)

 Women with mechanical heart valves

 Contraindication to heparin therapy, including:

 History of heparin induced thrombocytopenia

 Platelet count of less than 100,000 x 10^6/L

 Hemoglobin <= 90 g/L or a greater than 30 g/L drop in hemoglobin compared to last antepartum result

 History of osteoporosis

 History of steroid use (one week or more)

 Active bleeding

 Documented peptic ulcer within 6 weeks

 Heparin, bisulfite, or fish allergy

 Severe hypertension (systolic blood pressure [SBP] > 200 and/or diastolic blood pressure [DBP] > 120)

 Severe hepatic failure (International Normalized Ratio [INR] > 1.8)

 Women with serum creatinine > 80 and an abnormal 24 hour creatinine clearance.

 Contraindications to magnetic resonance imaging (MRI), including:

 Women with electrically, magnetically or mechanically activated implants

 Women with claustrophobia

 Women < 18 years of age


Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis

Summary: The purpose of this study is to determine whether Apremilast is safe and effective in the treatment of patients with rheumatoid arthritis, specifically in improving signs and symptoms of rheumatoid arthritis (tender and swollen joints, pain, physical function and structure) in treated patients who have had an inadequate response to Methotrexate.
Inclusion criteria: inclusion criteria:

 Must have a documented diagnosis of Rheumatoid Arthritis (1987 American College of Rheumatology Criteria) with onset of signs/symptoms of disease ≥ 4 months of duration from randomization.

 Must be receiving treatment on an outpatient basis.

 Must have active disease despite current methotrexate treatment as defined below:

 ≥ 6 swollen joints (66 swollen joint count) AND

 ≥ 6 tender joints (68 tender joint count)

 -. Must meet at least one of the four lab requirements below:

 High Sensitivity C-Reactive Protein (hsCRP) ≥ 10 mg/L

 Erythrocyte Sedimentation Rate (ESR) > 28 mm after the first 1 hour

 Positive for Rheumatoid Factor (RF)

 Positive for Anti-cyclic Citrullinated Peptide (anti-CCP) antibodies

 For participants participating in the Magnetic Resonance Imaging (MRI) assessment:

 • Must have Rheumatoid Arthritis joint involvement, as assessed by swollen joint counts in: 1) at least two Metacarpophalangeal (MCP) swollen joints on the same hand, or 2) at least one swollen Metacarpophalangeal (MCP) joint and swollen wrist on the same hand.

 Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.

 • Non-steroidal anti-inflammatory drugs (NSAIDs) and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.

 Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.

 Must meet the following laboratory criteria at screening:

 White blood cell count ≥ 3000/mm^3 (≥ 3.0 x 10^9/L) and < 14,000/mm^3 (< 14 x 10^9/L)

 Platelet count (≥ 100,000/μL ((≥ 100 x 10^9/L)

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

 Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase or serum glutamic-pyruvic transaminase (ALT/ SGPT) ≤ 2 x upper limit of normal (ULN). If initial test shows Aspartate aminotransferase (AST) or alanine aminotransferase (SLT) or 2 times the upper limit of normal (ULN), one repeat test is allowed during the screening period.

 Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the screening period.

 Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)

 Hemoglobin A1c ≤ 9.0%

 Negative for hepatitis B surface antigen

 Negative for hepatitis C antibody

 Males who engage in activity in which conception is possible must use protocol described barrier contraception while on Investigational Product and for at least 28 days after the last dose of Investigational Product.

 Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use protocol described contraception while on Investigational Product and for at least 28 days after taking the last dose or Investigational Product.

Exclusion criteria: :

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

 Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.

 Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.

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

 Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.

 Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.

 Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.

 Previous treatment with any cell depleting therapies, including investigational agents.

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

 Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.

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

 Pregnant women or nursing (breast feeding) mothers.

 Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c > 9.0%) or gastrointestinal (GI) disease.

 Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.

 Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.

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

 History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).

 History of alcohol, drug or chemical abuse within the 6 months prior to screening.

 Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

 Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

 Any condition that in the investigator's opinion would interfere significantly with the efficacy evaluations, including the pain and joint assessments (eg, fibromyalgia).

 For Magnetic Resonance Imaging (MRI) Only:

 Receiving medication(s) or will require medication(s) during the study that impact on vascular flow (eg, nitrates, calcium channel blockers, ergot containing drugs) on the day of the Magnetic Resonance Imaging (MRI test and in the investigator's judgement the subject cannot hold back from taking these medications on the day of the Magnetic Resonance Imaging (MRI) prior to the Magnetic Resonance Imaging (MRI) test. The subject can continue taking the medication(s) at any time after the Magnetic Resonance Imaging (MRI) test is completed, as clinically indicated and scheduled. Exclusions of antihypertensive and migraine medications can be determined after discussion with the Sponsor.

 Unable to undergo an Magnetic Resonance Imaging (MRI) examination, including but not limited to the presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip, pedicle screws, or any other metal contained in the body (eg, such as tattoos that contain metallic pigment, or metal in the eyes from metal grinding [eg, a metal worker, etc]), or severe claustrophobia, or any other contraindication to an Magnetic Resonance Imaging (MRI) as per local imaging center guidelines.

 Allergic or adverse reactions to gadolinium

 Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2 (based on the Modification of Diet in Renal Disease [MDRD] formula).

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

Apremilast 30 mg
Apremilast 20 mg
Placebo


Diagnostic Accuracy of Emergency Physician Performed Bedside Ultrasound in Suspected Acute Appendicitis

Summary: The aim of the study is to evaluate the diagnostic yield and accuracy of bedside emergency physician performed ultrasound in the diagnosis of acute appendicitis.
Inclusion criteria: inclusion criteria:

 Patient presented with the complaint of right lower abdominal pain

 Suspected acute appendicitis

Exclusion criteria: :

 Flank pain

 Previous appendectomy

 Pregnancy

 Unstable vital signs

 Frank peritonitis

 US performed before EP's examination


IV Double and Triple Concentrated Nicardipine for Stroke and ICH

Summary: Hypertension (high blood pressure) can often cause neurological worsening in patients with stroke, intracerebral hemorrhage and subarachnoid hemorrhage. Intravenous infusion of nicardipine (Cardene) for control of hypertension is FDA approved. The disadvantage of Nicardipine IV drip is the relative large volume of fluid needed (up to 150 cc/hr). The purpose of this study is to evaluate safety and efficacy of double or triple concentrated peripheral intravenous (IV) Nicardipine.
Inclusion criteria: inclusion criteria:

 Males or females, 18 years of age or older.

 Acute ischemic cerebral stroke (IS) with uncontrollable hypertension that may need to be controlled for the purpose of considering thrombolytic therapy or anticoagulation therapy.

 Intracerebral hemorrhagic (ICH) stroke patients, including subarachnoid hemorrhage (SAH) (surgically treated or not), any territory with an appropriate study (head CT scan or MRI scan) providing results consistent with this diagnosis, who may require the control of hypertension or control of blood pressure.

Exclusion criteria: :

 Allergy to Nicardipine or known hypersensitivity to Nicardipine.

 Chronic renal failure or Creatinine blood sample levels> 2.0.

 Impaired hepatic function defined as a two times value of liver enzymes.

 Severe left ventricular dysfunction defined as ventricular ejection fraction < 30%.

 Patients or authorized representative who refused be enrolled into this study.

 Advanced aortic stenosis.

 Pregnant or nursing women will not be enrolled in this study.

 No patient will be allowed to be enrolled in this study more than once.

 Patients may not be enrolled into other clinical studies during their involvement with this study.


To Evaluate the Use of ASTHMA IQ in a Primary Care Setting

Summary: There is a mounting body of evidence suggesting that there is a large disparity between the development and the actual implementation of guideline-driven asthma care in primary and specialty care practices. To address this disparity, the American Academy of Allergy, Asthma & Immunology (AAAAI) developed a unique, comprehensive and easy-to-use Web-based tool for clinicians who treat asthma patients called Asthma Specialist Tool to Help Manage Asthma and Improve Quality (Asthma-IQ). This study will examine whether the use of the Asthma IQ primary care tool will improve asthma care and asthma outcomes using a randomized trial of the Asthma IQ system versus usual asthma care in the primary care setting over 1 year. At the end of 1 year, all patients will be managed using the Asthma-IQ tool for an additional year to determine if the patients managed by usual care in the first year improve when managed in conjunction with Asthma-IQ. The primary endpoint to determine if the use of the Asthma IQ tool will improve asthma patient outcomes is quarterly assessments of Asthma Control Test (ACT) scores via automated / electronic patient survey. The secondary endpoint is asthma exacerbations and there are a number of exploratory endpoints to further define the clinical utility of the primary care version of Asthma-IQ. This study will involve recruiting approximately 20 family medicine offices with approximately 20 patients each, to conduct this randomized, multiple time point intervention trial. The necessary total recruited patient sample size is 200 per group. The results of this study will help determine the utility of Web-based tools to help manage chronic diseases such as asthma.
Inclusion criteria: inclusion criteria:

 Male or female patients, age 12 through 65 years at the time of screening;

 Written informed consent obtained from the patient prior to beginning study procedures;

 Documented clinical history of chronic persistent asthma requiring controller therapy;

 Able to complete the study period, including follow-up period, of up to approximately 2 years; and

 Willing to forego other forms of experimental treatment and study procedures during the study and for 30 days after the follow-up period is completed.

Exclusion criteria: :

 History of any disease, evidence of any current disease (other than asthma), any finding upon physical examination, or any laboratory abnormality, that, in the opinion of the investigator, may compromise the safety of the patient in the study or confound the analysis of the study;

 Lung disease other than asthma (e.g., chronic obstructive pulmonary disease, cystic fibrosis);

 Any disease or illness, other than asthma, that is likely to require the use of systemic corticosteroids during the study period;

 Current acute illnesses or evidence of significant active infection, such as fever ≥ 38.0°C (100.5°F) within 4 weeks of enrollment;

 Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives prior to screening, except omalizumab for asthma;

 Pregnancy at enrollment;

 Breastfeeding or lactating females;

 Elective major surgery planned from screening through study completion;

 History of cancer other than basal cell carcinoma of the skin or cervical carcinoma-in-situ treated with apparent success with curative therapy more than 1 year prior to enrollment;

 History of primary immunodeficiency;

 History within the past year of excessive alcohol intake or drug addiction.

 History of tobacco use of more than 10 pack years;

 Plans to move from the study site area during the duration of the study.

 Other protocol-defined inclusion/


Effects of Coronary Sinus Occlusion on Myocardial Ischemia (Pilot Study)

Summary: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in industrialized countries despite advances in medical, interventional, and surgical revascularization therapies. In both, acute myocardial infarction (AMI) and chronic stable disease, standard therapeutic approaches may fail to restore tissue perfusion. Indeed, a substantial number of chronic CAD patients may not be amenable to standard revascularization therapies or percutaneous coronary intervention (PCI) may fail to restore coronary artery patency following an acute vessel occlusion (no-reflow phenomenon, microvascular obstruction). As a consequence, the long pursued strategy of augmenting myocardial perfusion by diverting blood from the coronary venous system to an ischemic region (venous retroperfusion) has again gained attention during recent years. Occlusion of the coronary sinus (CSO) was introduced to provide retroperfusion by transient augmentation of coronary venous pressure. Different devices using CSO have been invented and evaluated in animal models and small clinical trials, e.g. intermittent CSO (ICSO) and pressure-controlled intermittent CSO (PICSO) which seem to be effective for myocardial salvage. However, they are not yet employed in clinical routine, and importantly, the exact underlying mechanisms by which retroperfusion due to CSO may reduce myocardial ischemia are not yet understood.~As natural bypasses, coronary collaterals are anastomoses without an intervening capillary bed between portions of the same coronary artery or between different coronary arteries that represent an alternative source of blood supply to a myocardial area jeopardized by ischemia. Collaterals of the heart can be assessed quantitatively by coronary pressure measurements, which have become the gold standard (collateral flow index, CFI=[Poccl-CVP]/[Pao-CVP]). Theoretically, augmentation of coronary sinus pressure by CSO with an increase of venous backflow reaches the upstream collateral circulation, which in turn could lead to improved collateral flow from non-ischemic area(s) to an occluded, ischemic myocardial region by upstream flow diversion. On the other hand, when considering the formula to calculate pressure-derived CFI, it seems that augmentation of coronary back pressure would rather impair collateral flow (since central venous pressure is coronary sinus pressure). However, the regional effect of a global increase in coronary sinus pressure is unlikely to be as uniform as the above formula implies, i.e., the response is more pronounced in some than in other vascular territories. In experimental studies using dogs (with abundant collaterals), elevation of coronary sinus pressure caused an augmentation of regional myocardial blood flow in the collateralized area. In contrast, when ICSO was performed in pigs (which possess no preformed collaterals), it increased the pressure distal of an occluded LAD but did not improve blood flow or left ventricular function.~In conclusion, experimental studies and pathophysiologic considerations suggest a necessary role of the collateral circulation for the beneficial effects of coronary sinus occlusion (CSO) observed in animals and humans; however, no clinical data are available so far on the effect of CSO on myocardial ischemia in the presence of varying collateral flow.~Study hypotheses~CSO decreases intra-coronary ECG ST-segment elevation during a 2-minute coronary occlusion.~The decrease in occlusive intra-coronary ECG ST elevation during CSO is directly proportional to CFI.~Coronary sinus oxygen saturation during coronary occlusion with CSO is directly proportional to CFI.
Inclusion criteria: inclusion criteria:

 Age > 17 years

 Stable angina pectoris, patient electively referred for coronary angiography

 Written informed consent to participate in the study

Exclusion criteria:

 Acute coronary syndrome; unstable cardio-pulmonary conditions

 Congestive heart failure NYHA III-IV

 Previous coronary bypass surgery

 Q-wave myocardial infarction in the area undergoing CFI measurement

 Anatomical variants not allowing coronary sinus occlusion

 Severe valvular heart disease

 Severe hepatic or renal failure (creatinine clearance < 15ml/min)

 Pregnancy

['intermittent coronary sinus occlusion']

['Coronary Artery Disease', 'Coronary Sinus', 'Circulation, Collateral', 'Ischemia', 'Collateral Flow Index']

Coronary Artery Disease
Coronary Sinus
Circulation
Collateral
Ischemia
Collateral Flow Index


Use of Beta Blockers in Elderly Trauma Patients

Summary: Advances in medical care have increased the proportion of elderly Americans and enabled them to remain more physically active. This has resulted in an unprecedented increase in the number of geriatric patients admitted to trauma centers. The elderly constitute 23% of trauma center admissions, but 36% of all trauma deaths. This disproportionately high mortality is attributable to a higher prevalence of pre-existing conditions, particularly, cardiac disease. Multi-system injuries result in critical cardiac stress. Although beta-blockade has been shown to decrease morbidity and mortality in patients at risk for myocardial infarction after elective surgery, their use in trauma patients with potential underlying cardiac disease has not been previously studied. We hypothesize that routine administration of beta-blockers after resuscitation will reduce morbidity and mortality in elderly trauma patients with, or at risk for, underlying cardiac disease.~This study is a randomized, prospective clinical trial. One cohort will receive routine trauma intensive care, and the other, the same care plus beta-blockade after completion of resuscitation. The primary outcome will be mortality. Secondary outcomes include MI, length of stay, organ dysfunction, cardiac, and other complications.~Changes in outcome may not be due to reduction in myocardial oxygen demand and heart rate. Laboratory studies demonstrate that circulating inflammatory cytokines contribute to cardiac risk in trauma patients, and their production is influenced by adrenergic stimulation. We will measure circulating IL-6, TNF alpha, IL-1beta, and measure NF-kB and p38 MAP kinase activation in peripheral blood leukocytes, and determine the effect of beta-blockade on the production of these inflammatory markers.~Finally, the wide variation in patient response to beta-blockers is attributed to genetic variability in the adrenergic receptor. Therefore, we will identify single nucleotide polymorphisms (SNPS) within the beta-adrenergic receptor, and determine their effects on mortality and response to beta-blockade. This study will provide the first randomized, prospective trial designed to reduce morbidity and mortality in elderly trauma patients at risk for cardiac disease. The laboratory and genetic component will provide additional insights that may explain treatment effects, lead to new therapeutic strategies, and have the potential to lead to additional areas of investigation.
Inclusion criteria: inclusion criteria:

 All trauma patients admitted to the ICU > 55 years of age with a primary diagnosis of injury will be screened on admission as study candidates.

Exclusion criteria: :

 Patients will be excluded if they have non-survivable injuries, are receiving comfort care only, have an advanced directive limiting aggressive care, heart block, severe asthma, bradycardia (< 60 bpm), are on beta-blocker therapy, or are having an acute or evolving myocardial infarction.

['Aged', 'Multiple Trauma', 'Cardiovascular Diseases']

Aged
Multiple Trauma
Cardiovascular Diseases