Warming Sensation Intensity and Acceptability of the Flavour, Local Tolerability of Paracetamol 500 mg + Pseudoephedrine 30 mg Syrup in Patients Suffering a URTI

Summary: This is an open label, in-use study to assess the warming sensation, acceptability and local tolerability of paracetamol 500 mg + pseudoephedrine 30 mg syrup, given as a single dose in subjects suffering from symptoms of an upper respiratory tract infection. The purpose is to evaluate the acceptability concerning a warming sensation effect and its potential benefit in the target population.~The primary objective is to assess the warming sensation caused by the excipient IFF flavor 316 282, in a syrup containing paracetamol 500 mg + pseudoephedrine 30 mg per 30 ml syrup. The syrup contains (0.15% w/v) warming flavor.~The Secondary Objectives are to assess subject acceptability of the syrup and the safety and tolerability of the syrup. The study will be run in fifty-six (56) subjects suffering from symptoms of an upper respiratory tract infection (URTI) for 7 days or less, e.g. nasal congestion associated with colds and flu symptoms such as pain, headache and/or fever. Subjects must have one or more symptoms per category:~mild to moderate body pain, headache, fever or sore throat~nasal congestion (blocked nose) with or without rhinorrhea (runny nose) or sneezing Adolescents will be included in the study population
Inclusion criteria: inclusion criteria:

 Subject must have one or more symptoms per category (see also screening assessment of cold symptoms, section 6.1):

 mild to moderate body pain, headache, fever or sore throat

 nasal congestion (blocked nose) with or without rhinorrhea (runny nose) or sneezing

Exclusion criteria: :

 Baseline sore throat pain of severe intensity, e.g. rated as 3 on a 4-point ordinal scale (0=not present, 1= mild, 2=moderate, 3=severe)

 Baseline dry cough of severe intensity, e.g. rated as 3 on a 4-point ordinal scale (0=not present, 1= mild, 2=moderate, 3=severe)

 Subject has a productive cough.

 History of hypersensitivity to any of the study drugs and the listed excipients or to drugs of similar chemical classes

 Subjects with allergic asthma.

 Use of any inhaler, medicated confectionary, throat lozenges, throat pastilles, sprays, any products with demulcent properties such as chewing gums and boiled sweets or mints, in the 6 hours prior to dosing.

 Use of any medication for sore throat containing a local anaesthetic within the 6 hours prior to dosing.

 Use of paracetamol, any NSAID or any oral nasal decongestant within 6 hours prior to dosing.

 Use of substances of abuse or antihistamines within 24 hours of dosing.

 Drinking of tea, coffee or other caffeinated beverages 1 hour prior to dosing.

 Suffering from hepatic or severe renal impairment, hypertension, hyperthyroidism, diabetes, heart disease or other acute or chronic medical condition that, in the opinion of the investigator, would put the subject at a higher risk or affect the conduct and/or the results of the study.

 Use of any antidepressants, monoamine oxidase inhibitors or beta-blocking drugs in the 28 days prior to dosing

 A history of alcohol abuse or subject admits to regular consumption of alcohol in excess of the recommended weekly limits of 21 units for females and 28 units for males.

 Subject is a current smoker of ≥10 cigarettes per day (or reports equivalent smoking habits using other tobacco products).

 Subject has smoked or chewed tobacco products within 12 hours of dosing.

 History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

['IFF flavor 316 282, Paracetamol, Pseudoephedrine']

IFF flavor 316 282
Paracetamol
Pseudoephedrine


Optimal Management of Women With Wrist Fractures

Summary: To evaluate the effectiveness of a multifaceted intervention (reminder and educational material) in improving the evaluation of osteoporosis follow-up care of post-menopausal women with wrist fractures by their primary care physicians. The intervention is directed at improving the gap in continuity of care between emergency/fracture clinics and family physicians, and reducing knowledge gaps.
Inclusion criteria: inclusion criteria:

 Postmenopausal women with low trauma distal radius fracture (confirmed by x-ray).

 Can be taking Didrocal (etidronate), Miacalcin (calcitonin),or hormone replacement therapy .

Exclusion criteria: :

 Women with fractures of the elbow, mid radius, scaphoid, or injury to wrists (without actual fracture).

 Significant cognitive impairment (which would preclude them from filling out simple questionnaires).

 Women already taking osteoporosis therapy, ie. either Fosamax (alendronate), Actonel (risedronate), or the selective estrogen receptor modulator, Evista (raloxifene).


Stenting Versus Best Medical Treatment of Asymptomatic High Grade Carotid Artery Stenosis

Summary: Background. Carotid artery stenting (CAS) recently has become an accepted method for treatment of patients with high-grade carotid artery stenosis, who are at an increased risk for surgical carotid endarterectomy (CEA). The reported rates of neurological complications of CAS substantially decreased during the past years, and the routine use of cerebral protection devices and low profile catheter systems have further increased the procedure´s safety. In the early 90's large surgical trials in North America and Europe (NASCET, ECST and ACAS) demonstrated superiority of CEA compared to best medical treatment for symptomatic and asymptomatic patients. Provided that the ongoing randomized controlled trials comparing CAS and CEA confirm equivalence between the these methods, CAS similar to CEA is applicable to symptomatic and asymptomatic patients with high grade carotid stenosis. However, particularly in asymptomatic patients, the indication for revascularisation remains debatable. Protected CAS is associated with a very low rate of neurological complications, which are below the AHA recommendation for treating asymptomatic patients (3%). However, the introduction of new vascular protective medications like statins and clopidogrel during the recent years substantially improved the spectrum of best medical treatment, and the findings of NASCET, ECST and ACAS with respect to best medical treatment may therefore not be applicable any more.~Study hypothesis and aims. Given the low frequency of spontaneous neurological complications, the preferable therapeutic approach to patients with asymptomatic high grade ( > 80%) carotid artery stenoses is currently unknown. Modern best medical treatment may manage to stabilize the atherosclerotic plaque, while CAS has the potential of resolving the carotid stenosis. Comparative data, however, are not available as yet. We hypothesized that protected CAS has a beneficial effect on occurrence of ipsilateral neurological complications and major adverse cardiac events in high-risk patients with asymptomatic > 80% internal carotid artery stenosis. Therefore, the aim of the present randomized controlled trial was to analyze neurological and cardiovascular outcome of patients treated with elective CAS plus best medical treatment compared to best medical treatment only.
Inclusion criteria: inclusion criteria:

 Atherosclerosis is the underlying disease

 Patients with an asymptomatic stenosis >80% (NASCET) with a documented progression of the degree of stenosis to >80% within 6 months with a very tight stenosis ≥90% at initial presentation with a >80% stenosis plus silent ipsilateral ischemia documented by CCT or MRI with ipsilateral >80% stenosis plus contralateral >80% stenosis or occlusion with >80% stenosis plus planned major surgery

 Neurologist´s explicit consent to potentially perform CAS

Exclusion criteria: :

 Inability to provide informed consent

 Underlying disease other than atherosclerosis (inflammatory or autoimmune disease)

 Traumatic or spontaneous carotid dissections

 Life expectancy <6 months

 Advanced dementia

 Advanced renal failure (serum creatinine >2.5 mg/dL)

 Unstable severe cardiovascular comorbidities (e.g. unstable angina, heart failure)

 Restenosis after prior CAS or CEA

 Allergy or contraindications to study medications (clopidogrel, statins, ASA)


Phase 1-2a Dose-Ranging Study of TLK286 in Combination With Docetaxel in Platinum-Resistant Non-Small Cell Lung Cancer

Summary: The purpose of this study is to determine the effectiveness and safety of TLK286 given intravenously once every three weeks in combination with docetaxel (Taxotere) in the treatment of patients with non-small cell lung cancer that is resistant to platinum-based chemotherapy.
Inclusion criteria: inclusion criteria include:

 Histologically confirmed non-small cell bronchogenic carcinoma, including squamous cell carcinoma, undifferentiated carcinoma, adenocarcinoma, mixed (adenocarcinoma with squamous cell carcinoma), bronchoalveolar carcinoma, or large cell carcinoma

 Stage IV or Stage IIIB

 Progressed during or after first-line therapies with platinum-containing regimens in the advanced or metastatic treatment regimen

 At least 18 years of age

 Good performance status (ECOG 0 to 1)

 Adequate liver, renal, and bone marrow function

Exclusion criteria:  include:

 Pregnant or lactating women

 Treatment with more than one cytotoxic therapy

 Prior radiation to the whole pelvis

 Unstable medical conditions such as uncontrolled cardiac arrhythmia

 Patients with known history of severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80

['TLK286 in combination with docetaxel']


Examining the Relationship Between Hormone Therapy (HT) and Cognitive Function (The WHIMS-ECHO Study)

Summary: This is a prospective, observational study of the cohort of older post-menopausal participants in the WHI Memory Study, a sub-cohort of participants in the WHI Hormone Trials. Annual cognitive assessments and ascertainment of cognitive impairment enable the continued monitoring of long-term effects of randomization to HT on cognition and identification of predictors of cognitive vulnerability and resilience in older women.
Inclusion criteria: inclusion criteria:

 Participated in the WHIMS study

Exclusion criteria:

 Non-English speaking

 Hearing Impaired

 Non-English speaking

 Hearing Impaired


POSTconditioning During Coronary Angioplasty in Acute Myocardial Infarction Study

Summary: The POST-conditioning during coronary angioplasty in Acute Myocardial Infarction (POST-AMI) trial will evaluate the usefulness of postconditioning in limiting infarct size and microvascular damage during the early and late phases after AMI.
Inclusion criteria: inclusion criteria:

 clinical evidence of myocardial infarction defined by the presence of ischemic chest pain lasting more than 30 minutes, with a time interval from the onset of symptoms less than 6 hours before hospital admission, associated with typical ST-segment elevation on the 12-lead ECG

 angiographic-detected culprit lesion with stenosis diameter >70% and TIMI flow grade <=1

Exclusion criteria: :

 previous acute myocardial infarction

 previous myocardial revascularization (angioplasty or coronary bypass)

 previous heart valve replacement

 previous heart transplant

 clinical instability precluding the suitability of the study

 cardiogenic shock or persistent hypotension (systolic blood pressure <100 mmHg)

 rescue angioplasty after thrombolytic therapy

 evidence of coronary collaterals (Rentrop grade>0) in the risk area

 advanced atrioventricular block

 significant bradycardia

 absence of sinus rhythm

 inability to lay flat (due to severe cardiac heart failure/respiratory insufficiency)

 history or clinical evidence of bronchospastic lung disease

 pregnancy

 known existence of a life-threatening disease with a life expectancy <6 months

 inability to give informed consent

 any contraindication to undergo cardiac-MRI, such as implanted metallic objects (cardiac pacemakers and/or implantable cardioverter defibrillator, implanted insulin pumps or any other type of electronic devices, cerebral clips, aneurysm clips) or any other contraindication to cardiac-MRI (such as claustrophobia)

['Postconditioning', 'Primary angioplasty and stenting without additional intervention']


Effects of Gaseous Cryotherapy on Knee ROM After TKA: A Feasibility Study

Summary: A pilot study was performed to investigate the feasibility of a large randomized controlled trial (RCT) to assess the effects of hyperbaric gaseous cryotherapy (HGC) on the change in knee flexion range of motion in the first two days after total knee arthroplasty.
Inclusion criteria: inclusion criteria:

 Planned unilateral TKA done at Verdun Hospital.

 Capacity to communicate in French or English.

Exclusion criteria: :

 Complications during or after the surgery.

 Inability to perform the tests due to other diseases.

 Contraindications to cryotherapy such as Raynaud's disease, cryoglobulinemia, hemoglobinopathy, polyneuropathy associated with temperature sensitivity deficits or allergy to cold.


Acute Kidney Injury in Neonates

Summary: Our first aim is to describe how common a sudden decrease in renal function happens in infants in a neonatal intensive care unit. We also want to see how a sudden loss of renal function affects survival. Finally, we will explore non-invasive markers to identify a sudden decrease in renal function from urinary samples.
Inclusion criteria: inclusion criteria:

 Families of infants (birthweight >1500g) be asked to participate in the study.

Exclusion criteria: :

 Infants with prenatal renal ultrasound diagnosis of severe hydronephrosis or other known renal abnormalities will be excluded


Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)

Summary: The objective of this study is to compare the long-term (six month) bronchodilator efficacy and safety of tiotropium inhalation capsules, salmeterol inhalation aerosol and placebo inpatients with COPD.
Inclusion criteria: inclusion criteria:

 Age ≥ 40 years.

 A diagnosis of relatively stable, moderate to severe COPD with:

 Screening FEV1 ≤ 60% of predicted normal value (calculated according to European Community for Coal and Steel (ECCS) criteria and screening FEV1/FVC ≤ 70%

 Smoking history ≥ 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent)

 Ability to be trained in the proper use of the HandiHaler® device and Metered Dose Inhaler (MDI).

 Ability to perform all study related tests including the Shuttle Walking Test, acceptable pulmonary function tests, including Peak expiratory flow rate (PEFR) measurements, and maintenance of diary card records.

 Ability to give written informed consent in accordance with Good Clinical Practice and local regulations.

Exclusion criteria: :

 Clinically significant diseases other than COPD.

 Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion, will be excluded.

 All patients with a serum glutamic oxaloacetic transaminase (SGOT) > 80 IU/L, serum glutamic pyruvic transaminase (SGPT) > 80 IU/L, bilirubin >2.0 mg/dL or creatinine > 2.0 mg/dL will be excluded regardless of clinical condition.

 A recent history (i.e., one year or less) of myocardial infarction.

 Any cardiac arrhythmia requiring drug therapy or hospitalisation for heart failure within the past three years.

 Inability to abstain from regular daytime use of oxygen therapy for more than 1 hour per day.

 Known active tuberculosis.

 History of cancer within the last five years (excluding basal cell carcinoma)

 History of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.

 Patients who have undergone thoracotomy with pulmonary resection.

 Any upper respiratory infection in the past six weeks prior to the screening visit or during the run-in period.

 Current participation in a pulmonary rehabilitation programme or completion of a pulmonary rehabilitation programme in the six week prior to the screening visit.

 Known hypersensitivity to anticholinergic drugs, salmeterol, or any of the components of the lactose powder capsule or MDI delivery systems.

 Known symptomatic prostatic hypertrophy or bladder neck obstruction.

 Patients with known narrow-angle glaucoma.

 Current treatment with cromolyn sodium or nedocromil sodium.

 Current treatment with antihistamines (H1 receptor antagonists).

 Oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day.

 Current use of β-blocker medication.

 Current treatment with monoamine oxidase inhibitors or tricyclic antidepressants.

 Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.

 Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count > 600mm3.

 History of and/or active significant alcohol or drug abuse.

 Concomitant or recent use of an investigational drug within one month or six half lives (whichever is greater) prior to the screening visit.

 Changes in the pulmonary therapeutic plan within the six weeks prior to the screening visit.

 Inability to comply with the medication restrictions specified in Section 4.2 of the trial protocol

['Tiotropium inhalation powder capsules', 'Salmeterol inhalation aerosol', 'Placebo inhalation aerosol', 'Placebo inhalation powder capsules']

Tiotropium inhalation powder capsules
Salmeterol inhalation aerosol
Placebo inhalation aerosol
Placebo inhalation powder capsules

['Pulmonary Disease, Chronic Obstructive']


Nonmyeloablative Conditioning and Transplantation for Patients With Refractory Systemic Lupus Erythematosus (SLE)

Summary: The main goal of the study is to determine if bone marrow transplant (BMT) from a less specific pool of donors in combination with high dose cyclophosphamide can induce remission of refractory systemic lupus erythematosus.
Inclusion criteria: inclusion criteria:

 Four or more American College of Rheumatology (ACR) criteria for the classification of SLE or 4 or more of the SLICE criteria

 Involvement of one or more of the following organ systems: renal, neurologic, hematologic, cardiac, pulmonary, gastrointestinal

 A lack of response to corticosteroids in moderate-to-high doses, and to either an equivalent degree of immunosuppression with azathioprine, methotrexate, cyclosporin, tacrolimus, belimumab, rituximab, mycophenolate mofetil, and/or appropriate other treatment

 Patients should be eligible for transplantation according to the BMT Policy Manual

Exclusion criteria: :

 Age less than 18 years and over 75 years

 Any risk of pregnancy

 Patients who are preterminal or moribund

['Cyclophosphamide', 'Fludarabine', 'Tacrolimus', 'Mycophenolate Mofetil', 'Rabbit antithymocyte globulin', 'Total body irradiation', 'Allogeneic bone marrow transplant']

Cyclophosphamide
Fludarabine
Tacrolimus
Mycophenolate Mofetil
Rabbit antithymocyte globulin
Total body irradiation
Allogeneic bone marrow transplant

['Lupus Erythematosus', 'Graft-versus-host Disease']

Lupus Erythematosus
Graft-versus-host Disease


Using Sodium Lactate Ringer's Injection Resuscitate Septic Shock Patients

Summary: Using sodium lactate Ringer's injection resuscitate septic shock patients and Compared with other solution, in order to make clear whether can improve the prognosis.
Inclusion criteria: inclusion criteria:

 diagnosis in patients with septic shock

Exclusion criteria: :

 pregnant women and nursing mothers

 severe liver failure with child class C

 using Linezolid

 pheochromocytoma

 hematologic malignancy

 using epinephrine

 during CVVH treatment

["sodium lactate Ringer's injection(Baxter, ShangHai, China)", 'Compound Sodium Chloride Injection (CR Double-Crane, Beijing, China)']

['Severe Sepsis With Septic Shock', 'Lactate']


Probiotics and Corticosteroids for Treating Periodic Fever, Aphthous Stomatitis, Pharyngitis, Cervical Adenitis (PFAPA)

Summary: The purpose of study is to see if adding probiotics to corticosteroid treatment for children with PFAPA could improve the health and daily of patients through reduction in febrile period frequency and length, along with concomitant reduction of associated symptoms. Current standard of care incorporates the administration of corticosteroids; however, while limiting the symptoms associated with PFAPA, corticosteroid use has been shown to increase the frequency at which these symptoms occur. Investigators hypothesize that administration of probiotics along with corticosteroids will work to decrease the frequency at which the febrile episodes occur. Additionally, probiotics may decrease the maximal fever experienced during these episodes, amount of corticosteroid needed to control the symptoms, average length of the episodes, and the number of patients who ultimately undergo tonsillectomy due to unsuccessful treatment with medication.
Inclusion criteria: inclusion criteria:

 diagnosis or confirmation of diagnosis of PFAPA from Dr. Bennett based on clinical or laboratory data

 is or will be undergoing treatment for PFAPA at CCMC

 agrees to the consent and, if necessary, assent forms

 is between 1 and 12 years of age

Exclusion criteria: :

 is currently taking another probiotic regularly (>=2 times/ week)

 is allergic to ingredients in the probiotic or placebo

 may react adversely to the probiotic due to any form of immune deficiency or chronic disease including pulmonary, renal, cardiac disorders including underlying structural heart disease, gastrointestinal disease, or diabetes

 is not a proficient English speaker

 does not agree to the consent and/or assent forms

 patients who use antibiotics or have used them within a month of the study start

['Lactobacillus acidophilus and Bifidobacterium lactis', 'Placebo']

['Periodic Fever', 'Aphthous Stomatitis', 'Pharyngitis', 'Cervical Adenitis']

Periodic Fever
Aphthous Stomatitis
Pharyngitis
Cervical Adenitis


Acute Anterior Cruciate Ligament Rupture; RecOnsTruction Or Repair?

Summary: To investigate the hypothesis that suture repair of a ruptured vkb, combined with a dynamic intraligamentary stabilization and microfracture of the femoral notch, results in at least equal effectiveness compared with an ACL reconstruction using autologous hamstring in terms of functional recovery one year postoperatively in terms of a patient self-reported outcome related to be able to conduct daily and sporting activities. Secondary, the evaluation of clinical outcomes, self-reported by the patient outcomes, osteoarthritis, rehabilitation time required for return to daily and sporting activities and levels of sporting activity which has returned in patients with status after an ACL rupture and suture repair augmented with a dynamic intraligamentary microfracture and stabilization of the femoral notch in comparison with an anterior cruciate ligament reconstruction with the ipsilateral hamstring graft.
Inclusion criteria: inclusion criteria:

 Sportive, active patient (Tegner score =/>5)

 Age above 18 untill 30 years at time of inclusion

 Primary rupture of the anterior cruciate ligament, evidence by history (acute trauma, clicking sensation, swelling within a few hours, instability) and physical examination (positive Lachman, anterior drawer test and/or Pivot shift)

 Primary rupture indicated by MRI

 No associated ligamentuous disorde of the knee, evidenced by history, physical examination, x-ray or MRI)

 Time span between anterior cruciate ligament rupture and operation no longer than 21 days

 Willingness to comply to advised rehabilitation protocol supervised by (NFVS registrated) sports physiotherapist

Exclusion criteria: :

 Infection

 Known hypersensitive response for materials used (Cobalt, chroom, nickel)

 Serieus pre-existing malaligment of leg indicated for surgery

 Tendency for excessive scar tisseu formation, such as arthrofibrosis

 History of previous surgery on leg indicated for surgery

 History of removal of tendon on leg indicated for surgery

 Muscular, neurological or vascular disorders negatively affecting healing or rehabilitation

 Cartilage injury requiring (some kind of) cartilage repair surgery (such as microfracture or cell therapy)

 Arthrosis more dan ICRS grade 2 evidenced by x-ray

 Long(er) term use of relevant medication, such as prednisolon or cytostatica

 Pregnancy

 Know osteoporosis


Preliminary Study of Dornase Alfa to Treat Chest Infections Post Lung Transplant.

Summary: Patients who have undergone lung transplantation are at an increased risk of developing chest infections due to long-term medication suppressing the immune response. In other chronic lung diseases such as cystic fibrosis (CF) and bronchiectasis, inhaled, nebulised mucolytic medication such as dornase alfa and isotonic saline are often used as part of the management of lung disease characterized by increased or retained secretions. These agents act by making it easier to clear airway secretions, and are currently being used on a case-by-case basis post lung transplantation.~To the investigators knowledge, these agents have not been evaluated via robust scientific investigation when used post lung transplant, yet are widely used in routine practice. Patients post lung transplant must be investigated separately as they exhibit differences in physiology that make the clearance of sputum potentially more difficult when compared to other lung diseases. Lower respiratory tract infections are a leading cause of hospital re-admission post lung transplant. Therefore, this highlights the need for a randomized controlled trial. The aim of this study is to assess the efficacy of dornase alfa, compared to isotonic saline, in the management of lower respiratory tract infections post lung transplant. Investigators hypothesize that dornase alfa will be more effective than isotonic saline.~The effect of a daily dose of dornase alfa and isotonic saline will be compared over a treatment period of 1 month. Patients admitted to hospital suffering from chest infections characterized by sputum production post lung transplant will be eligible for study inclusion. Patients will be followed up through to 3 months in total to analyze short-medium term lasting effect. Investigators wish to monitor physiological change within the lung non-invasively via lung function analysis whilst assessing patient perceived benefit via cough specific quality of life questionnaires. These measures will be taken at study inclusion and repeated after 1 month and 3 months. Day to day monitoring will be performed via patient symptom diaries, incorporating hospital length of stay and exacerbation rate. The outcomes of this study have the potential to guide clinical decision-making and highlight safe and efficacious therapies.
Inclusion criteria: inclusion criteria:

 Post bilateral sequential lung transplant

 Capable of performing airway clearance techniques / nebulisers

 Pulmonary exacerbation as defined by Fuchs et al

 Must be productive of sputum

 Able to provide informed consent within 48 hours of presentation.

 *Fuchs Scale(8): Treatment with / without parenteral antibiotics for 4/12 signs and symptoms:

 Change in sputum

 New or increased haemoptysis

 Increased cough

 Increased dyspnoea

 Malaise, fever or lethargy

 Temp above 38

 Anorexia or weight loss

 Sinus pain or tenderness

 Change in sinus discharge

 Change in physical examination of the chest

 Radiographic changes indicative of pulmonary infection

 Decrease in pulmonary function by 10 % or more

Exclusion criteria: :

 Paediatric transplant <18yrs

 Single lung transplant - native lung physiology may confound outcome measures

 Interstate - unable to complete follow up

 Unable to perform lung function testing

 Unable to complete subjective outcome measures- unable to read English fluently

 Critically unwell / intensive care unit / ventilator dependent

 Within 2 months of transplant date *Cystic Fibrosis will be stratified

['Lung Transplant Infection', 'Lower Respiratory Tract Infection']

Lung Transplant Infection
Lower Respiratory Tract Infection


Study of Combination of Cetuximab and Radiotherapy Added to the Standard Treatment for Oesophageal Adenocarcinoma

Summary: The purpose of this study is to determine whether the addition of the combination between cetuximab and radiotherapy to the standard chemotherapy for resectable oesophageal cancer is safe and adds efficacy.
Inclusion criteria: inclusion criteria:

 Histologically proven resectable adenocarcinoma of the lower oesophagus and gastric-oesophageal junction

 Tumour stage: T2-3 N0-1 M0, as assessed by endoscopic ultrasound and CT-scan of thorax and abdomen and ultrasound neck region. For the patients treated in this study the gastro-oesophageal junctional tumors will be staged as oesophageal tumors with respect to their lymphnode metastases.

 Age >18y and written informed consent after at least 4 days of deliberation time from the moment the patient information has been given and has been explained.

 Weight loss < 10% in 0.5 yr

 WHO performance status 0-1

 No prior radiotherapy or chemotherapy for the adenocarcinoma of the oesophagus

Exclusion criteria: :

 Previous malignancy other than basal cell carcinoma of the skin or local resection for cervical carcinoma in situ.

 Inadequate organ function as defined by:

 Inadequate haematology (Hb < 5,5 mmol/L (red blood cell transfusions are allowed to increase the Hb at the discretion of the investigator) - neutrophils < 1,5 109/L -platelets <100*109/L),

 Liver enzyme elevation (bili > 1,5*ULN - ASAT > 2,5*ULN - ALAT > 2,5*ULN) or

 Impaired renal function (creatinine clearance by cockcroft < 60 cc/min)

 Proteinuria >1,0gr/24hr

 Tumour stage: M1a and/or tumour length > 8 cm and/or > 5 cm radially

 Major surgery within 4 weeks prior to the start of study treatment

 Bleeding disorder

 Known allergy to one of the study drugs used

 Use of any substance known to interfere with the chemotherapy clearance

 Previous radiotherapy to the chest

 Significant concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments

 Uncontrolled angina pectoris; cardiac failure or clinically significant arrhythmias

 Continuous use of immunosuppressive agents

 Concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine

 Prior exposure to anti-EGFR targeting agents.

 Hearing loss > 25 dB under normal

 Neurotoxicity > CTC grade 1

 Pregnancy or breast feeding

 Patients (M/F) with reproductive potential not implementing adequate contraceptive measures

['cetuximab', 'radiotherapy to oesophageal tumour']

cetuximab
radiotherapy to oesophageal tumour


A Study Comparing the Efficacy and Safety of IDP-120 Gel in the Treatment of Acne Vulgaris

Summary: The primary objective of this study is to compare the efficacy, safety, and tolerability of IDP-120 Gel to IDP-120 Component A, IDP-120 Component B, and IDP-120 Vehicle Gel in subjects with moderate to severe acne vulgaris.
Inclusion criteria: inclusion criteria:

 Male or female at least 9 years of age and older

 Written and verbal informed consent must be obtained.

 Subject must have a score of moderate or severe on the Evaluator's Global Severity assessment at the screening and baseline visit

 Pre-menses females and women of childbearing potential must have a negative urine pregnancy test at screening and baseline visits

 Subjects must be willing to comply with study instructions and return to the clinic for required visits.

Exclusion criteria: :

 Any dermatological conditions on the face that could interfere with clinical evaluations

 Any underlying disease(s) or some other dermatological condition of the face that requires the use of interfering topical or systemic therapy or makes evaluations and lesion count inconclusive

 Subjects with a facial beard or mustache that could interfere with the study assessments

 Subjects who are unable to communicate or cooperate with the Investigator

 Subjects with any underlying disease that the Investigator deems uncontrolled and poses a concern for the subject's safety while participating in the study

['IDP-120 Gel', 'IDP-120 Component A', 'IDP-120 Component B', 'IDP-120 Vehicle Gel']

IDP-120 Gel
IDP-120 Component A
IDP-120 Component B
IDP-120 Vehicle Gel


A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of the Safety and Efficacy of Ceftriaxone and Doxycycline in the Treatment of Patients With Seronegative Chronic Lyme Disease

Summary: Lyme disease is the most common tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. It may exist in a chronic form and be the result of: 1) persistent infection by B. burgdorferi; 2) damage caused by the original infectious process; or 3) the presence of coinfection with another organism transmitted by Ixodes ticks. The purpose of this study is to determine the safety and effectiveness, in seronegative patients, of intensive antibiotic treatment in eliminating symptoms of Chronic Lyme Disease (CLD).
Inclusion criteria: inclusion criteria:

 You may be eligible for this study if you:

 Are at least 18 years of age.

 Are seronegative for antibodies against B. burgdorferi antigens by Western Blot at enrollment.

 Have documented history of acute Lyme disease.

 Have had a rash (erythema migrans) that resembles a bullseye. This skin aberration usually occurs after a tick bite in late spring, summer, or early fall and is sometimes accompanied by fatigue, fever, headache, mild stiff neck, arthralgia or myalgia.

 Have had one or more clinical features typical of Lyme disease acquired in the United States (see technical summary)

 Have had one or more of the following symptoms and conditions that have persisted for at least 6 months (but less than 12 years) and are not attributable to another cause or condition: a) widespread musculoskeletal pain and fatigue that began coincident with or within 6 months following initial infection with B. burgdorferi. b) certain neurologic symptoms including memory impairment and nerve pain, beginning within 6 months following initial infection with B. burgdorferi.

 Have had a physician-documented history of prior antibiotic treatment with a currently recommended antibiotic regimen.

Exclusion criteria: :

 You will not be eligible for this study if you:

 Have previously enrolled in this study.

 Are pregnant, lactating, or unable to use birth control measures during the treatment period of this study.

 Are taking chronic medication that could interfere with evaluation of symptoms.

 Are taking or have taken various medications that could interfere with the evaluation of symptoms (see technical summary).

 Are hypersensitive to ceftriaxone or doxycycline.

 Have active inflammatory synovitis.

 Have another disease that could account for symptoms of acute Lyme disease.

 Have another serious or active infection.

 Are unable to tolerate an IV.

 Have tested positive for Borrelia DNA in plasma or cerebrospinal fluid at the time of initial evaluation for study.

 Have tested seropositive by Western Blot (these patients may be offered enrollment in seropositive study).


The Effect of Subdural Drain Placement After Burr Hole Evacuation of Chronic Subdural Haematomas on Recurrence: a Prospective Randomised-controlled Multi-centre Study

Summary: This is a prospective randomised-controlled multi-centre trial based in Hong Kong to determine whether temporary subdural drain placement after burr hole evacuation of a chronic subdural haematoma can reduce the risk of recurrence. Consecutive patients, 60 years old or above, diagnosed to have symptomatic chronic subdural haematoma and indicated for burr hole operative drainage will be randomly allocated into one of two groups: (1) for intra-operative subdural drain placement (intervention group) or (2) not for drain placement (control group). Using web-based software block randomisation with an allocation ratio of 1:1 will be conducted. Instructions to use or not to use a drain will be contained in a sealed envelopes labelled with sequential study numbers.~Intra-operatively, if the surgeon-in-charge judges that after burr hole evacuation of the haematoma the patient's condition is unsafe for drain placement, the subject will be excluded from the study. Otherwise, randomisation will be performed at this juncture by the opening of the sealed envelop. The procedure involves placing a prefabricated silicon drain into the subdural space according to a standard protocol and will be removed on the second post-operative day at the bedside. Subjects in whom the operating surgeon judges that drain placement is unsafe will be excluded from the study. Drainage is undertaken passively by hanging the collection bag at the bedside in a dependent position. In addition to general demographic, clinical and radiological presentation data, potential risk factors for recurrence will be documented. Serial computed tomography brain scans will be arranged (before discharge, at four weeks and six months) and the occurence of significant subdural haematoma recurrence requiring repeat operative drainage at six months will be recorded. Other outcome measures to be determined at regular time intervals for a total follow-up period of six months (upon discharge, at four weeks and six months) include: functional performance in terms of the extended Glasgow Outcome Scale and modified Rankin Scale, added neurological deficit, death and other surgery-related complications. All outcomes will be documented by the trial investigators or by the responsible clinician. The data obtained will be analysed according to the principle of intention to treat.~Hypothesis: compared to burr-hole evacuation of chronic subdural haematoma alone (control), the additional placement of a subdural drain after evacuation (intervention) will reduce the risk of recurrence requiring repeat surgery.
Inclusion criteria: inclusion criteria:

 Patients diagnosed to have symptomatic chronic subdural haematoma confirmed by a computed tomography or magnetic resonance imaging brain scan.

 Ethnic Chinese

 Age >/= 60 years-old

 Reasonable expectation of completion of outcome measures at follow-up

 Written informed consent

Exclusion criteria: :

 Unsalvageable patients: fixed and dilated pupils after resuscitation or signs of brainstem herniation that precludes definitive therapy.

 When the operating surgeon judges that drain placement may be hazardous or to be of limited benefit e.g. readily expanded brain in young patients.

 History of previous cranial neurosurgical procedure.

 On concurrent glucocorticoid therapy.

 Suspected intracranial hypotension syndrome.

 Blood dyscrasia:

 Use of antiplatelet medication e.g. aspirin or warfarin without adequate reversal or observation for drug effect to wear off (at least 5-7 days).

 Thrombocytopenia: platelet level <100 x 109/l

 Coagulopathy: prothrombin time PT >12sec or, activated partial thromboplastin time (APTT) >37.4 sec

 End-stage renal/ hepatic failure.

 Known or strong suspicion of alcohol or illicit drug abuse.

 Pregnancy

 Known epilepsy

 Any neurological or non-neurological condition independent from SAH that might influence the functional outcome or other efficacy outcome measures

['Silicon subdural drain placement after burr hole evacuation of chronic subdural hematoma']

['Chronic Subdural Hematoma', 'Subdural Drain']

Chronic Subdural Hematoma
Subdural Drain


Trial on the Ideal Duration of Oral Antibiotics in Children With Pneumonia

Summary: To determine, in children hospitalized with pneumonia, if an extended duration of oral antibiotics (10 days) will be superior to a shorter duration (3 days) of antibiotics in improving clinical outcomes.~Secondary Aims:~Describe the prevalence of respiratory viruses and bacteria at presentation.~Investigate the depression, anxiety and stress scores (DASS21) and quality of life scored (QOL) by parents of the children during admission, pre-discharge and post discharge and at follow-ups.
Inclusion criteria: inclusion criteria:

 Children admitted with severe pneumonia as defined by the presence of all the following as defined as below:

 3 months to 59 months old

 History of cough and/or shortness of breath

 Unwell for <= 7 days -Increased respiratory rate ( ≥ 50/min if ≤12 months old, ≥ 40/min) or retractions,-

 Any of the following signs/symptoms are present at examination that would necessitate admission: chest retractions, cyanosis, saturation< 92% on air, poor feeding or lethargy

 Documented fever (axillary /central temp ≥ 38/38.5°C) within 24 hrs of admission

 Abnormal CXR with presence of alveolar infiltrates

 Responds to IV antibiotics by the first 72 hrs and able to go home with oral antibiotics i.e. no more hypoxia and afebrile and reduced respiratory symptoms

Exclusion criteria: :

 Children who (a) are transferred from another hospital (b) refuse blood taking (c) have a doctor diagnosis of asthma or recurrent wheezing illness (d) have a diagnosis of bronchiolitis i.e. wheezing in a child with a CXR with no consolidation (e) not acute illness ( ie >7 days) (f) unable to come for follow-up (g) not community acquired pneumonia e.g. aspiration pneumonia (h)complicated pneumonia with effusion, pneumothorax, clinical suspicion of necrotizing pneumonia (i)PICU admission or use of Non-invasive ventilation (j)significant comorbidities that can increase the risk of having a complicated pneumonia- (k) need for use of other antibiotics like anti-staph or macrolides (l)extra-pulmonary infection e.g. meningitis (m)allergy to penicillin (n) unable to tolerate oral antibiotics (o) underlying illness that can predispose to recurrent pneumonia

 -

['Amoxicillin-Potassium Clavulanate Combination', 'Placebo']


Study of the Efficacy of Local Analgesia as an Adjunct to General Anesthesia in Thyroidectomy and Parathyroidectomy

Summary: We aim to study the effect of local anesthetic when used in conjunction with general anesthesia during thyroidectomy or parathyroidectomy. We hypothesize there is equivalent pain control between bilateral superficial cervical plexus block and local wound infiltration when used in conjunction with a general anesthetic.
Inclusion criteria: inclusion criteria:

 Patient ≥ 18 years old

 Surgical indication for parathyroidectomy or thyroidectomy

Exclusion criteria: :

 Patients < 18 years old

 Patient with history of chronic opioid use

 Patient with chronic pain syndromes

 Patient with allergy to marcaine

['Superficial Cervical Plexus Block', 'Local Wound Infiltration', '0.9% saline', 'Marcaine']

Superficial Cervical Plexus Block
Local Wound Infiltration
0.9% saline
Marcaine

['Thyroid Neoplasms', 'Goiter, Nodular', 'Thyroid Nodule', "Graves' Disease", 'Hyperparathyroidism']

Thyroid Neoplasms
Goiter
Nodular
Thyroid Nodule
Graves' Disease
Hyperparathyroidism


Should the Joint Capsule of the Painful Stiff Shoulder be Ruptured During Intra-articular Hydraulic Distension?

Summary: The purpose of the study is to compare the efficacy of intra-articular hydraulic distension (IHD) for the treatment of painful stiff shoulders between capsule-rupturing and capsule-preserving IHDs.
Inclusion criteria: inclusion criteria:

 shoulder discomfort for at least one month

 limited range of motion of the glenohumeral joint in at least two directions

Exclusion criteria: :

 systemic inflammatory joint disease

 radiological evidence of bony abnormality of the shoulder

 full-thickness rotator cuff tear

 acute systemic medical illness

 history of major trauma or surgery involving the shoulder

 contraindication to intra-articular, local anesthestic injection

['Capsule-Preserving Intra-articular Hydraulic Distension', 'Capsule-Rupturing Intra-articular Hydraulic Distension']


The Effect of Plaquenil on Serum Inflammatory Markers and Goiter in Euthyroid Young Women With Hashimoto's Thyroiditis

Summary: Hashimoto's thyroiditis (HT) is a common form of autoimmune thyroid disease, which affects up to 2% of general population. The annual incidence of HT worldwide is estimated to be 0.8 - 3.5 cases per 1000 persons. The thyroid gland attacked by a variety of cell- and antibody-mediated immune processes. Various auto-antibodies may be present against TPO and Tg, and ADCC is a substantial factor behind the apoptotic fall-out of HT. Activation of cytotoxic T-lymphocytes in response to cell-mediated immune response affected by helper T-cells is central to thyrocyte destruction. Recent studies showed higher pro-inflammatory cytokines in serum of patients with HT, and suggested HT is associated with regulatory T-cells dysfunction, imbalance of ratio of Th1 cell and Th2 cell, overexpression of Th17 cells.~Several studies suggested that pregnant women with HT, even at euthyroid state had higher risk of spontaneous miscarriage, more frequent post-partum depression and higher depressive, anger, and total mood disturbance risk compared to those without HT. Presence of thyroid auto-antibodies is also associated with negative pregnant outcomes including gestational hypertension, late abortion, fetal death, premature delivery and neonatal respiratory distress. Neonates from mothers with ATD have higher rate of transient hypothyroidism. Children of mothers with ATD had higher risk of positive serum thyroid auto-antibodies and development of goiter and thyroid dysfunction. However, there is no suggested treatment for subjects with HT who have normal thyroid function. Low-iodine diet and regularly follow-up were suggested.~Plaquenil (hydroxychloroquine) is an anti-malarial agent, and has been used to treat several autoimmune diseases, including lupus erythematosus and rheumatoid arthritis for more than a century. It reduced lymphocytes, production of auto-antibodies, cytokines, and immune mediators, NK cell activity, and inhibits antigens presenting to CD4 T-cells of B cells, dendritic cells and monocytes.~This study focuses on the effect of Plaquenil on thyroid auto-antibodies, inflammatory markers, cytokines, and goiter size in euthyroid women with HT.
Inclusion criteria: inclusion criteria:

 Newly diagnosed (within 1 year) Hashimoto's thyroiditis by positive serum anti-TPO antibody or anti-thyroglobulin antibody

 Euthyroid state by serum free T4 and TSH level within normal limit

Exclusion criteria: :

 Pregnant, planning pregnant within 1 year, or lactating women

 Renal insufficiency, abnormal liver function test

 Hematologic diseases: anemia, agranulocytosis, thrombocytopenia

 G6PD deficiency, porphyria cutaneous tarda

 Allergy to 4-aminoquinoline compounds

 Known retinopathy or visual field defect disorders

 Already receive immunosuppression therapy


Mol Epi GrAS in Nicaragua

Summary: The purpose of this study is to determine the epidemiology of throat isolates of group A streptococci among 3-15 year-old children with pharyngitis (sore throat) living in Leon, Nicaragua.
Inclusion criteria: inclusion criteria:

 1. All children 3- to 15-years old with pharyngitis who are seen at a participating site will be invited to participate.

Exclusion criteria: :

 Subjects whose parents are unable or unwilling to provide informed consent will be excluded from the study.

 Children who are 13 years or older and unable or unwilling to provide informed consent will be excluded form the study.


CRP-guided Antibiotic Treatment in COPD Exacerbations Admitted to the Hospital

Summary: Rationale: Acute exacerbations are key events in chronic obstructive pulmonary disease (COPD), resulting in poorer quality of life. Causes include irritants, viruses and bacterial pathogens. These exacerbations are often treated with a combination of corticosteroids, bronchodilators and antibiotics, but the benefit of antibiotic therapy remains controversial. Several trials studying antibiotic treatment in AECOPD showed conflicting data, with several large studies failing to demonstrate superiority of antibiotic therapy over placebo. Other trials indicated that antibiotic therapy is effective in patients who have at least two of the following symptoms: increased dyspnoea, increased sputum volume and increased sputum purulence. Ever since sputum purulence has been used as a predictive marker in AECOPD, a strategy that has been integrated in the GOLD guideline for treatment of AECOPD. However, the color of sputum reported by patients is not always reliable and inspection of sputum is not always possible. Several serum biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) are now available. In a recent trial of doxycycline in addition to systemic corticosteroids for patients hospitalized with AECOPD we found that CRP might be valuable as a marker predictive of response to antibiotic treatment in AECOPD.
Inclusion criteria: inclusion criteria:

 Age 40 or over. No upper age limit will be employed.

 Written informed consent obtained.

 AECOPD according to the GOLD guideline. An exacerbation of COPD is defined as an event in the natural course of the disease characterized by a change in the patient's baseline dyspnoea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.

 Criteria for hospital admission according to the GOLD: marked increase in symptoms (i.e. resting dyspnoea), severe underlying COPD, onset of new physical signs (cyanosis, edema), failure to respond to initial medical management, significant co morbidities, frequent exacerbations, newly occurring arrhythmias, diagnostic uncertainty.

 Former of current smoker with a minimum smoking history of 10 pack years.

 Patients have to be capable of ingesting oral medication.

 Patients have to be mentally capable of participating in the study (able to complete questionnaires and perform lung function tests).

 Life expectancy ≥ 30 days.

Exclusion criteria: :

 Pregnant or lactating women, or women of childbearing age not using an acceptable method of contraception.

 Pretreatment with corticosteroids (cumulative dose >210 mg) for the present exacerbation.

 Progression or new radiographic abnormalities on the chest X-ray or CT scan compatible with pneumonia.

 bronchiectasis (HRCT confirmed).

 Cystic fibrosis.

 Tuberculosis.

 Immunodeficiency disorders such as AIDS, humoral immune defect, ciliary dysfunction etc., and the use of immunosuppressive drugs (>30 mg prednisolone/day maintenance dose or equivalent for more than 4 weeks).

 Recent or unresolved lung malignancy.

 Other disease likely to require antibiotic therapy, such as recurrent sinusitis or urinary tract infection.

 Significant gastrointestinal or other conditions that may affect study drug absorption.

 Class III or IV congestive heart failure or stroke.

 Newly diagnosed pulmonary embolism

['COPD', 'Exacerbation', 'Bronchitis', 'Sputum', 'C-Reactive Protein']

COPD
Exacerbation
Bronchitis
Sputum
C-Reactive Protein


Bedside Sedation for the Prevention of Post Dural Puncture Headache

Summary: Dural or lumbar puncture (LP), the passing of a needle into the space of the spinal cord, is a common procedure in everyday clinical practice. The most common use for LP is to measure the spinal fluid pressure and sample spinal fluid for laboratory analysis. However, it is also used for therapeutic purposes, such as administering chemotherapy or spinal anesthesia.~A notorious side effect of dural puncture is headache that ranges from mild to debilitating and may last for several days following the procedure. Among diagnosed patients, 39% experience at least 1 week of impaired ability to perform activities of daily living. The likelihood of developing a headache after dural puncture depends on a number of factors. As fluid leak is assumed to be the culprit mechanism in this headache strategies to minimize the leak seem to offer the best path to lowering the incidence of headache after diagnostic LP, the commonest clinical context of dural puncture in medical practice.~Lumbar puncture is a highly stressful event for most patients. As both pain and anxiety cause adrenergic stimulation, they also cause an increase in ICP. We believe that this mild increase in ICP, occurring before the puncture as well as during the puncture itself may exacerbate the pressure difference between the CSF space and the epidural space and so worsen the CSF leak Furthermore, this excess pressure, although mild, might cause the dural puncture hole to widen slightly and so further augment the leak and possibly even prolong it. Furthermore, the very anticipation of pain causes a rise in neurotransmitters that may cause a sensitization effect and worsen pain. This increase in adrenergic drive as well as the sensitization to pain can be effectively blunted by the periprocedural use of mild IV sedation. Benzodiazepines, with their sedative-hypnotic qualities are well suited for this task.~This study aims to test the effect of mild peri-procedural IV sedation using Midazolam on the rates of headache after diagnostic LP.~Patients undergoing a diagnostic LP will be randomized into two groups. Group 1 will undergo the procedure as routinely practiced. Group 2 will be given Midazolam IV 10-5 minutes prior to the procedure and undergo the same diagnostic procedure. All patients in the study will remain under observation in the hospital for at least 6 hours.~Patients will be evaluated for headache and specifically for headache. Clinical follow up will continue for 72 hours by administering a short questionnaire over the telephone.
Inclusion criteria: inclusion criteria:

 18-50 years old

 Undergoing diagnostic LP for any indication for the first time

Exclusion criteria: :

 COPD

 Any known chronic pulmonary disease

 Acute febrile illness

 Persistent headaches

 Known sensitivity to Benzodiazepines

 Current or prior substance abuse disorder

 Cognitive decline


Femoral Arterial Access With Ultrasound Trial

Summary: This study is designed to evaluate the routine use of vascular ultrasound as an aid for proper placement of a femoral arterial sheath during cardiac catheterization and peripheral arterial angiography.
Inclusion criteria: inclusion criteria:

 Adults age 18 and over

 Patients undergoing left heart catheterization or peripheral arterial angiography from the retrograde femoral approach

 Willingness and ability to sign consent form

 Scheduled to have procedure performed by operator trained in the ultrasound technique

Exclusion criteria: :

 Access from a site other than the common femoral artery

 Nonpalpable femoral pulses

 Creatinine > 3.0 mg/dl, unless already on dialysis

 Prisoners

 Pregnant women

 Unable or refusal to sign consent form

 Patients undergoing emergent cardiac catheterization for ST segment elevation myocardial infarction or unstable acute coronary syndrome

 Equipment unavailable

['Real-time Ultrasound Guidance (Site-Rite 5 or 6 machine)']

['Vascular Access Complications', 'Cardiac Catheterization', 'Peripheral Vascular Disease']

Vascular Access Complications
Cardiac Catheterization
Peripheral Vascular Disease


The Importance of Different Modularity of the Polyethylene Insert for Tibial Component Migration and Adaptive Bone Remodeling After Uncemented Total Knee Arthroplasty Using Trabecular Metal Technology (TMT) Zimmer NexGen®, (Monoblock vs. Modular Design)

Summary: In a prospective randomised study two uncemented tibial components with different polyethylene modularities (Trabecular Metal Technology (TMT) Zimmer NexGen® monobloc and TMT Zimmer NexGen® modular) used for total knee arthroplasty (TKA) is evaluated. Both tibial component coatings are designed to provide excellent condition for bone ingrowth.~The differences between the two tibial components are evaluated by measurements of migration of the tibial component assessed by Radiostereometric analysis (RSA) and measurements of the adaptive bone remodeling of the proximal tibial assessed by dual energy X-ray absorptiometry (DEXA).
Inclusion criteria: The participants of the study are patients that have been scheduled for a primary TKA using the usual indications for TKA at the Department of Planned Elective Surgery Z, Gentofte Hospital.

 inclusion criteria:

 Severe osteoarthrosis of the knee with indication for a TKA.

 Age between 40 and 70 years.

Exclusion criteria: :

 Diseases affecting the bone metabolism (osteoporosis, Pagets disease, hyperparathyreoidism etc.).

 Patients estimated not to be able to understand the Information to patients papers or do not want to participate in the study.

['Zimmer NexGen® Trabecular Metal Technology (TMT), Monoblock', 'Zimmer NexGen® Trabecular Metal Technology (TMT), Modular']


A Clinical Pathway for Nursing Home Acquired Pneumonia

Summary: Nursing home residents are frequently transferred to hospital for management of pneumonia. This often leads to hospital related complications and is a burden on the acute care health system. The purpose of this study is to assess whether managing residents with pneumonia and lower respiratory tract infection on site in the nursing home can reduce hospital admissions and can reduce complications and improve quality of life for residents. We have randomized residents with nursing home acquired pneumonia to on-site management, using a clinical pathway, versus usual care.
Inclusion criteria: inclusion criteria:

 Symptoms or signs of lower respiratory tract infection as defined by standardized criteria.

Exclusion criteria: :

 Residents were excluded if they were not expected to live longer than 30 days from the date of enrollment, had a previous anaphylactic or serious allergic reaction to quinolones, had advanced directives that they are not be transferred to hospital for treatment.

['a clinical pathway nursing home acquired pneumonia']

['Pneumonia', 'Lower Respiratory Tract Infection']

Pneumonia
Lower Respiratory Tract Infection


Evaluation of Stool Tagging for Improved Patient Compliance

Summary: Computed tomography (CT) colonography has gained widespread multi-disciplinary interest as an evolving noninvasive colorectal screening examination, with the potential of improved patient compliance. The investigator's prior work demonstrated that the bowel preparation was the least tolerable aspect of colorectal evaluation when compared to the CT colonography and optical colonoscopy procedures. Stool tagging could provide a more gentle and efficient bowel preparation, with fewer false positives due to retained stool-mimicking polyps.~The researchers hypothesize that image quality and patient preference will vary with stool tagging concentration and dosing schedule. The researchers propose to evaluate specific stool tagging protocols with the following aims:~AIM 1: Perform a randomized trial of three specific stool tagging protocols using barium and iodine at CT colonography in a well-characterized cohort of patients undergoing colorectal evaluation.~AIM 2: Analyze the CT colonography and optical colonoscopy data to assess differences across stool tagging protocols for the outcome measures of patient preference, image quality in the presence of tagging, and diagnostic reader performance.~The researchers will use specific variations in stool tagging techniques to determine the best image quality of CT data (e.g., homogenous tagging of fluid and stool), and highest patient acceptability, as well as evaluate the adequacy of preparation for same-day colonoscopy. Diagnostic reader performance will focus on the accuracy for detecting all neoplastic lesions including colon cancers, adenomatous polyps, sessile adenomas and flat adenomas. Most importantly, these results will help inform the design of a larger trial of an optimized CT colonography technique in a community setting.
Inclusion criteria: inclusion criteria:

 Patients who are 45 to 80 years old for routine screening colonoscopy

Exclusion criteria: :

 Patients with inflammatory bowel disease

 Patients with polyposis syndromes

 Pregnant women

 Patients over 350 pounds

 Patients with bright red blood per rectum

 Patients who have a contraindication to undergo outpatient colonoscopy, including patients on blood thinners, prior myocardial infarction (MI) in the last six months, history of congestive heart failure (CHF), history of arrhythmia, patients too weak to transfer themselves from a bed to a chair, or patients with severe constipation who would require a two day bowel preparation.

 All subjects will undergo informed consent by the St. Luke's institutional review board (IRB). Referred subjects will be asked if they are interested in the study and those responding affirmatively will be transferred to a recruiter to learn about the study and begin the consent process if interested.

['Imaging procedure of CT colonography']


Evaluation of Lithium and It's Effect on Clinically Localized Prostate Cancer

Summary: Laboratory testing has suggested that lithium may decrease the incidence of certain types of cancer, including prostate cancer. Additional research has suggested that lithium decreases prostate cancer tumor size over time. This study will investigate the effect of lithium on men with prostate cancer.
Inclusion criteria: inclusion criteria:

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

 Subjects with histologically confirmed local adenocarcinoma of the prostate who have elected to proceed with radical prostatectomy as primary curative therapy.

 Subjects having no prior administration of lithium or lithium containing medications within 90 days of study enrollment.

 Subjects >/= 18 years of age.

 ECOG (Eastern Cooperative Oncology Group) performance status of </= 1.

 Adequate renal function defined as GFR (Glomerular Filtration Rate) >/= 50 mL/min.

 Use of adequate contraception

 ECG (Electrocardiogram) within normal limits.

 Subjects must agree not to take any new vitamin supplements or herbal remedy during the study period.

 Subjects must be able to safety take lithium carbonate for at least 4 weeks before scheduled prostatectomy.

Exclusion criteria: :

 Subjects who have received any investigational medication within 30 days of first lithium dose.

 Subjects currently receiving, or who have had previous hormonal, chemotherapy or radiotherapy for prostate cancer.

 Subjects with known brain metastases.

 History of allergic reactions attributed to compounds of similar chemical or biologic composition to lithium carbonate.

 Uncontrolled intercurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.


Capecitabine and 131I-huA33 in Patients With Metastatic Colorectal Cancer

Summary: The purpose of this clinical trial is to determine whether it is safe to treat patients with advanced colorectal cancer, with humanised A33 antibody tagged with radioactive iodine (131I-huA33) in combination with chemotherapy (capecitabine).
Inclusion criteria: inclusion criteria:

 Metastatic colorectal cancer.

 Histologically or cytologically proven colorectal cancer.

 Measurable disease on CT scan with at least one lesion >/= 2cm diameter (to allow adequate infusion imaging).

 Expected survival of at least 4 months.

 ECOG performance status 0-2.

 Vital laboratory parameters should be within normal range including:

 Neutrophils >/= 1.5 x 10^9/L;

 Platelets >/= 150 x 10^9/L;

 Serum bilirubin </= 34 micromol/L;

 Calculated creatinine clearance > 50 ml/min.

 Age >/= 18 years.

 Able and willing to give valid written informed consent.

Exclusion criteria: :

 Previous treatment with capecitabine.

 Untreated active metastatic disease to the central nervous system (new or enlarging lesions on CT or MRI), or within 3 months of treatment (ie surgery or radiotherapy) for brain metastases.

 Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.

 Liver involvement with metastatic disease > 50% liver volume.

 Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).

 Previous external beam irradiation except if: (i) it was for standard adjuvant pelvic radiation for rectal cancer; (ii) it was for localised irradiation for skin cancer; or (iii) the sum total of all previous external beam irradiation port areas is not greater than 25% of the total red marrow.

 Previous treatment with a monoclonal antibody or antibody fragment AND a positive huA33 human anti-human antibody (HAHA) titre.

 Concomitant treatment with systemic corticosteroids. Topical or inhalational corticosteroids are permitted.

 Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.

 Lack of availability of the patient for clinical and laboratory follow-up assessment.

 Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.

 Pregnancy or breastfeeding.

 Women of childbearing potential: Refusal or inability to use effective means of contraception.

['Capecitabine', '131I-huA33 (131-Iodine on humanised monoclonal antibody A33)']


Comparison of Autologous Mesenchymal Stem Cells and Mononuclear Cells on Diabetic Critical Limb Ischemia and Foot Ulcer

Summary: Objective:~To compare the effect and safety of autologous transplantation of bone marrow mesenchymal stem cells(MSCs) and mononuclear cells(MNCs) on Diabetic patients with Critical Limb Ischemia and Foot Ulcer.~Methods:~patients were randomized into the A group and the B group by use of a randomization table. One lower limb in A group or in B group was selected randomly for MSCs or MNCs transplantation as MSCs or MNCs group, the other lower limb in the same patient was selected for placebo（normal saline ,NS）injection as NS group.~The whole procedures of this clinical trial were blinded to both patients and investigators.Patients in both groups received the same ordinary treatment. Meanwhile, MSCs and MNCs were transplanted into the impaired lower limbs respectively. Follow-up index include: efficacy (pain,ulcer healing rate, lower limb amputation rate and ,ankle-brachial index,Transcutaneous oxygen pressure,magnetic resonance angiography) and safety (infection of the injection site, immunological rejection, and tumour generation).
Inclusion criteria: inclusion criteria:

 Age from 40 to 70 years

 Type 2 diabetic patients

 bilateral critical limb ischemia(ABI from 0.30 to 0.60)

 at least with one foot ulcer

Exclusion criteria: :

 dry gangrene above the ankle or moist gangrene

 malignant tumor

 severe coronary,cerebral and renal vascular disease

['Autologous Transplantation', 'Diabetic Foot']

Autologous Transplantation
Diabetic Foot


The Role of Angiotensin Type I Receptor in the Regulation of Human Coronary Vascular Function

Summary: The renin angiotensin system (RAS) plays an important physiological and pathophysiological role in the control of blood pressure and plasma volume. Inhibition of the RAS is useful in the treatment of hypertension, cardiac failure and in some patients with myocardial infarction. Several recent clinical trials with angiotensin converting enzyme inhibitors (ACEI) have shown that they also reduce the incidence of myocardial infarction, but the mechanisms underlying this anti-ischemic effect are poorly understood. ACEI reduce angiotensin II synthesis and prevent bradykinin degradation. Results from ongoing studies in the Cardiology Branch (Protocol 95-H-0099) designed to investigate the link between ACEI and the vascular endothelium indicate that ACEI improve both endothelial dysfunction and metabolic coronary vasodilation, an effect that is partially mediated by bradykinin. The current protocol is designed to investigate whether the beneficial effects of ACEI on endothelial function are also partly due to inhibition of angiotensin II. The recent development of selective angiotensin II type 1 (AT1) receptor antagonists allows us to specifically examine the effects of angiotensin II on vasomotor activity.
Inclusion criteria: Patient must be over 18 years of age requiring diagnostic cardiac catheterization will participate.

 Women on chronic estrogen therapy are eligible for the study.

 Patients investigated for chest pain syndrome with normal coronary arteries with and without risk factors for atherosclerosis, patients with coronary artery disease, and patients with heart failure.

 No patients with unstable angina; significant left main disease (greater than 50% stenosis); Recent myocardial infarction (less than 1 month); Pregnancy, lactation; Allergy to losartan; Renal failure (creatinine greater than 2.5 mg/dl); Inability to withdraw ACE inhibitors.
Exclusion criteria:

['Angiotensin II type 1 receptor antagonists']

['Hypertension', 'Atherosclerosis', 'Heart Failure, Congestive', 'Myocardial Infarction']

Hypertension
Atherosclerosis
Heart Failure
Congestive
Myocardial Infarction


Comparison of the Effect of Magnesium Sulfate and Dexamethasone on Postoperative Sore Throat After Spinal Surgery in Prone Position With Tracheal Intubation: a Double-blind, Randomized, Noninferiority Clinical Trial

Summary: The purpose of this study is to compare the effect of magnesium sulfate and dexamethasone on postoperative sore throat after spinal surgery in prone position with tracheal intubation.
Inclusion criteria: inclusion criteria:

 ASA I-II patients aged between 20 and 65 year undergoing 1 or 2 level posterior spinal fusion in prone position with tracheal intubation

Exclusion criteria: :

 preexisting hoarseness or sore throat, upper respiratory tract infection

 steroid therapy or immunocompromised patients

 chronic treatment with calcium channel blocker or magnesium

 allergy to magnesium sulphate

 Cormack-Lehane grade 3,4 or patients who are expected to difficult intubation

 fail to tracheal intubation at first trial

 reduced kidney function

 Diabetes mellitus


Dyspnea and Biomarkers in a Prehospital Setting

Summary: In patients presenting with acute dyspnea in a pre-hospital setting, the early and correct diagnosis may present a significant clinical challenge. Physical examination, chest radiography, electrocardiography, and standard biological tests often fail to accurately differentiate heart failure (HF) from pulmonary causes of dyspnea. Timely differentiation of HF from other causes of dyspnea may permit the early institution of appropriate medical therapy. Brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) have been proposed as early markers of HF and demonstrated to be useful for diagnosing and excluding HF in the emergency department. A combination of BNP or NT-proBNP testing and standard clinical assessment has been suggested to be superior to either tool used in isolation. Some previous studies have also suggested that quantitative capnometry (QC) may be useful in differentiating between cardiac and obstructive causes of respiratory distress. Therefore, the investigators hypothesized that a new combination of NT-proBNP testing, standard clinical assessment, and partial pressure of end-tidal CO2 (PetCO2) would optimize evaluation and differentiation of acute dyspnea in a pre-hospital setting.~The aim of this study was to determine the accuracy of combination of QC, NT-proBNP, and clinical assessment in differentiating acute HF from obstructive pulmonary disease (COPD/asthma) as a cause of acute dyspnea in pre-hospital emergency setting.
Inclusion criteria: inclusion criteria:

 patient had to present with shortness of breath as the primary complaint (defined as either the sudden onset of dyspnea without history of chronic dyspnea or an increase in the severity of chronic dyspnea)

Exclusion criteria: :

 age <18 years

 history of renal insufficiency, trauma, severe coronary ischemia (unless patient's predominant presentation was dyspnea), and other causes of dyspnea:

 pneumonia

 pulmonary embolism

 carcinoma

 pneumothorax

 pleural effusion

 intoxications (drugs)

 anaphylactic reactions

 upper airway obstruction

 bronchial stenosis

 gastroesophageal reflux disorder

 according to the history, clinical status, and additional laboratory tests available in pre-hospital setting (D-dimer, troponin, C-reactive protein)

['Dyspnea', 'Heart Failure', 'Asthma', 'COPD']


Phase I Clinical Human Tolerability Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

Summary: In the tests, small sample of clinical study about Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 ( Recombination EC Allergen） healthy adults was carried out.~24 healthy adults were included as study objects, they were randomly divided into four groups of different Recombinant Allergen EC dose (1, 5, 10μg/mL, maximum tolerated dose 20μg/mL, 6 person/dose) for single arm intradermal injection.~The main examination items :vital signs (breathing, heart rate, blood pressure, body temperature ) of each volunteer at 15min, 30min, 1h, 2h, 4h, 8h, 24h, 48h, 72h, 96h after injection, skin reactivity (redness and/or induration) diameter of injection sites,local reaction ( rash, pain, itching, and skin and mucous membranes ) ,a variety of adverse events,routine blood,routine urine, liver and kidney function, ECG and chest X-ray films before and 7 days after intradermal injection .~Preliminary evaluation of safety and tolerability of Recombinant Allergen EC applied in humans, which can provide a safe dosage range for phase II clinical study.
Inclusion criteria: inclusion criteria:

 Aged from 18 to 40 years old, age difference is not more than 10 years old within the same batch of healthy volunteers, the male to female ratio of cases is 1:1. Body mass index should be in the range of 20 to 27 Body Mass Index BMI: weight (Kg)/ height (M2);

 Agreed to participate in the test and sign the informed consent;

 Subjects should comply with the requirements of the clinical trial protocol and be followed;

 Subjects have no history of TB (Tuberculosis)or family history of tuberculosis;

 People have no pulmonary tuberculosis or extrapulmonary tuberculosis,respiratory symptom or systemic symptoms;

 People have no tuberculosis focus after examination by X-ray chest radiograph and sputum bacilli;

 Subjects have no acute or chronic disease, acute infectious diseases, dermatoses or skin allergy caused by various reasons;

 Physical condition: have no history of heart, liver, kidney, gastrointestinal tract, nervous system, or metabolic disturbance, etc. ECG, blood pressure, heart rate, respiratory status and lab test indexes including blood, urine, liver and kidney function, etc are all normal within 4 weeks before screening;

 No close contacts of tuberculosis;

 Subjects have not participated in other clinical drug trials or inoculated against other prophylactic and immune globulin in the nearly 3 months;

 Temperature is normal;

 Stop smoking, drinking and drinking contains caffeinated.

Exclusion criteria: :

 Health people have close contacts of TB (Tuberculosis)patients, especially excreter in 3 weeks before selection;

 Suffering from any other serious disease, e.g. during cancer treatment, autoimmune disease, progressive atherosclerosis, diabetes accompanied with complications, chronic obstructive pulmonary disease (COPD) needing oxygen therapy, acute or progressive liver or kidney disease, congestive heart failure, etc.;

 People have history of allergy, convulsions, epilepsy, cerebropathy, neurological symptoms and signs;

 Patients who have impaired or abnormal immune function, e.g. patients treated with immunosuppressor or immunopotentiator, received immunoglobulin preparation or blood products or plasma extraction outside the gastrointestinal tract in 3 months, human immunodeficiency virus or related diseases;

 Acute febrile illness and infection;

 Taking part in other clinic trials;

 Subjects have participated in any other clinical drug trials in 3 months before our clinical tests;

 Allergic constitution, e.g. patients have allergic history to two or more kinds of drugs or food, or drug components;

 Substance abuse and alcoholics ;

 Pregnant or breast feeding women;

 Mental or physical disability;

 Informed leavers;

 Any other cases that may influence the test evaluation.


Automated Algorithm Based Analysis of Phonocardiograms of Newborns

Summary: The purpose of this double-blind pivotal clinical utility study is to determine on a large patient population whether heart murmurs can be reliably detected with high sensitivity and specificity using a locked, automated algorithm-based phonocardiogram analysis (also referred to as computer aided auscultation (CAA)).~Each patient is auscultated and diagnosed independently by a medical specialist. Additionally, for each patient, an echocardiogram is performed as the gold-standard for determining heart pathologies. The CAA results are compared to the findings of the medical professionals as well as to the echocardiogram findings.~Hypothesis: The specific (locked) CAA algorithms used in this study are able to automatically diagnose pathological heart murmurs in premature babies and newborns with at least the same accuracy as experienced medical specialists.
Inclusion criteria: inclusion criteria:

 any premature baby or newborn

 parental approval for study participation

Exclusion criteria: :

 none

['Heart Murmurs', 'Mitral Valve Prolapse', 'Systolic Murmurs']

Heart Murmurs
Mitral Valve Prolapse
Systolic Murmurs


Screening for Asymptomatic Portal Vein Thrombosis and Portal Hypertension in Patients With Philadelphia Negative Myeloproliferative Neoplasms

Summary: This study involves screening for portal vein thrombosis and portal hypertension in patients with Philadelphia negative myeloproliferative neoplasms (MPNs). These include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis.~Portal vein thrombosis and portal hypertension are serious complications that are often seen in myeloproliferative patients. These complications are usually diagnosed when patients become symptomatic, and are often already at an advanced stage. They can further progress to cause non-reversible damage to the liver, also called cirrhosis of the liver. As a result of this, patients often accumulate fluid in the abdomen which is ascites; and can develop swelling of veins in the lining of the esophagus known as varices. If untreated, varices have the risk of rupturing resulting in life-threatening bleeding. When diagnosed at an advanced stage, the treatment is usually supportive therapy and there are no treatments available at present which can reverse these conditions.~This study is looking at screening for these two conditions using Doppler ultrasound and upper gastrointestinal endoscopy.
Inclusion criteria: inclusion criteria:

 One of the three classical Philadelphia negative myeloproliferative neoplasms (polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF)) diagnosed according to WHO or International working group-Myelofibrosis research and treatment (IWG-MRT) criteria

 Palpable spleen length greater than 5 cm below the costal margin in MF (including primary MF or post-polycythemia vera MF (PPV-MF) post-polycythemia vera ET (PPV-ET)) or palpable spleen of any size in patients with PV or ET.

 Ability to understand and willing to sign a written consent form.

 Age 18 years or older at time of consent.

Exclusion criteria: :

 Known history of portal vein thrombosis

 Known history of Budd-chairi syndrome

 Known history of oesophageal varices

 Known history of cirrhosis from any cause

 Known history of active bleeding

['Upper gastrointestinal endoscopy and Doppler ultrasound']

['Myeloproliferative Neoplasms (MPN)', 'Polycythemia Vera (PV)', 'Essential Thrombocythemia (ET)', 'Myelofibrosis (MF)']

Myeloproliferative Neoplasms (MPN)
Polycythemia Vera (PV)
Essential Thrombocythemia (ET)
Myelofibrosis (MF)


Cytomegalovirus Reactivation in Non Immunocompromised Patients Undergoing Cardiac Surgery

Summary: We hypothesized that the stress of cardiac surgery and cardiopulmonary bypass can cause reactivation of a latent CMV infection and that reactivation might be more prevalent in patients with complicated post-operative course. The study aims are:~To study whether cardiac surgery is a trigger for latent CMV reactivation and to compare reactivation rate between sub groups of patient with complicated post-operative course and non complicated post operative course.~To study the relationship between expression IL28 SNP rs12979860 and the risk of CMV replication in the non immunocompromised patient undergoing cardiac surgery.
Inclusion criteria: inclusion criteria:

 Patients admitted for cardiac surgery.

 Age 18 and above.

Exclusion criteria: :

 1. Immunosuppressed patients including: HIV, active cancer, biological chemotherapy, steroid use equivalent to prednisone dosage above 1 mg/Kg a day, post organ transplantation.


Analysis of Lyme Disease Lesions

Summary: This study will analyze cells from erythema migrans lesions, the bull's eye rash of Lyme disease. Little is known about what happens in the skin when it is infected with Borrelia burgdorferi, the bacteria that cause Lyme disease. This study will examine and compare laboratory findings in skin biopsies from people with Lyme disease and from healthy normal volunteers to try to better understand the infection.~Healthy volunteers and people with untreated erythema migrans rash who are 18 years of age or older may be eligible for this study.~All participants undergo a clinical examination, blood tests, between two to four skin biopsies (removal of a small piece of tissue for laboratory examination), and complete two health questionnaires. The biopsies are taken from the erythema migrans lesion in patients with Lyme disease and from skin on the legs, forearms, buttocks, or side from healthy volunteers. To collect the tissue, the skin at the biopsy site is numbed with injection of a local anesthetic and a sharp instrument is then used to remove a round plug of skin about the size of a pencil eraser. The wound may be closed with one or two sutures, or allowed to heal without sutures. The sutures are removed after a week to 10 days.~Patients with Lyme disease receive treatment for their condition. In addition, at the time the sutures are removed and at 4 weeks, 6 months, and 12 months after their first visit they fill out a questionnaire and have additional blood tests.
Inclusion criteria: inclusion criteria:

 Patients:

 Age greater than or equal to 18 years

 Diagnosis of EM - an expanding annular lesion, at least 5 cm in diameter on a person with a history of exposure to the disease.

 Exposure is defined as having been (less than or equal to 30 days before onset of EM) in wooded, brushy, or grassy areas (i.e., potential tick habitats) in an area in which Lyme disease is endemic.

 A history of tick bite is not required.

 The area of the erythema migrans lesion is suitable for biopsy. This excludes biopsies on the face, neck, scalp, and over the tibia.

 Not know to be positive for RPR, HIV, HBsAg or HCV

 Able to give consent

 Healthy Volunteers:

 Age greater than or equal to 18 years

 Not positive for RPR, HIV, HBsAg or HCV.

 Able to give consent

Exclusion criteria: :

 Patients:

 Antibiotic therapy for the current episode of Lyme disease

 Oral corticosteroids within the past 2 weeks

 History of severe skin disease (such as psoriasis, atopic dermatitis) in the last year.

 Diagnosis of diabetes, active cancer, or autoimmune diseases.

 Investigational drugs in the past month

 History of forming large thick scars after skin injuries or surgery

 History of excessive bleeding after cuts or procedures or on anticoagulation.

 Use of steroid cream/ointment at the rash.

 Healthy Volunteers:

 History of Lyme disease, or serological evidence for Lyme disease

 No oral corticosteroids within the past 2 weeks

 History of severe skin disease (such as psoriasis, atopic dermatitis) in the last year.

 Diagnosis of diabetes, cancer, autoimmune diseases.

 Investigational drugs in the past month

 History of forming large thick scars after skin injuries or surgery

 No history of excessive bleeding after cuts or procedures or on anticoagulation.

['Erythema Migrans Lesions', 'Erythema Migrans']

Erythema Migrans Lesions
Erythema Migrans


Role of the Microbiome in Graves' Orbitopathy

Summary: Graves' orbitopathy (GO), also known as thyroid eye disease, affects approximately 3 million people in Europe with an estimated socioeconomic burden of 6.4 billion euros per annum. GO is a complication of Graves' disease which is an autoimmune disease and the commonest cause of an overactive thyroid gland. The treatment of GO remains unsatisfactory and the majority of patients report long-term impairment of quality of life. The effects of gut derived antigens, from micro-organisms and nutrients, on the autoimmune response will be tested in the animal model by probiotic and contra-biotic intervention. In the Indigo interventional trial the investigators will add to the standard anti-thyroid drug treatment (ATD) a specifically designed probiotics (LAB4, Cultech Ltd., West Glamorgan, UK) to assess whether it is possible to modify the microbiome in GD patients and improve their immunological status.
Inclusion criteria: inclusion criteria:

 Group A: Untreated Graves' hyperthyroidism (or within 4 weeks of initiating ATD treatment)

 definition hyperthyroidism: TSH decreased, FT4 and /or FT3 increased

 definition Graves': diffusely enlarged thyroid gland either by palpation or echograpy, and/or homogeneous thyroid uptake at scintigraphy, or positive TSHRAb

 first episode or recurrence of Graves' hyperthyroidism

 minimal or no eye signs, defined as lid retraction / lid lag but no other signs.

 Planned treatment with antithyroid drugs either titration regimen or block-and-replace regimen for 18 months.

 Group B. Untreated Graves' hyperthyroidism (or within 4 weeks of initiating ATD treatment) with overt signs of GO as defined by EUGOGO1

 Mild GO: patients whose features of GO have only a minor impact on daily life insufficient to justify immunosuppressive or surgical treatment. They usually have only one or more of the following: minor lid retraction (<2 mm), mild soft tissue involvement, exophthalmos <3 mm above normal for race and gender, transient or no diplopia, and corneal exposure responsive to lubricants)

 Moderate-to-severe GO: Patients without sight-threatening GO whose eye disease has sufficient impact on daily life to justify the risks of immunosuppression (if active) or surgical intervention (if inactive). Patients with moderate-to-severe GO usually have any one or more of the following: lid retraction R2 mm, moderate or severe soft tissue involvement, exophthalmos >3 mm above normal for race and gender, inconstant, or constant diplopia.

 Sight -threatening GO: Patients with dysthyroid optic neuropathy (DON) and/or corneal

Exclusion criteria: :

 Previous or planned treatment with 131I or thyroidectomy (A&B); sight threatening GO requiring decompression (B); drugs interfering with the natural course of GO (A&B): steroids, immunosuppressants, thiazolidinediones, antibiotics / antifungals / antivirals (both topical and systemic for at least 4 weeks prior to recruitment to the study); acute diarrhea illness (gastroenteritis for at least 4 weeks prior to recruitment to the study); Drugs interfering with thyroid function (A&B): amiodarone, lithium, iodine supplements; Drug or alcohol abuse (A&B); no informed consent (A&B); Age less than 18 (A&B); Pregnancy (A&B).


Safety and Performance Study of Large Hole Vascular Closure Device

Summary: The purpose of this Clinical Investigation is to gather feasibility data on the clinical use of the VIVASURE CLOSURE DEVICE™ in relation to safety, and to confirm its performance to percutaneously close femoral arterial puncture sites in the range of 18-24 F, post endovascular procedures.
Inclusion criteria: inclusion criteria:

 Over 18 years of age.

 Each patient, or his or her guardian or legal representative, is willing to give informed consent.

 Clinically indicated for an endovascular procedure involving access through the femoral artery, with an access puncture of 18 - 24 F.

 Females who are not pregnant or lactating, and not planning to become pregnant ≤ 12 months. A pregnancy test may be performed to confirm this.

Exclusion criteria: :

 There will be no exclusion of patients from this trial in respect of race, co-existent disease or concomitant therapy, with the exception of those listed below.

 Severe acute non-cardiac systemic disease or terminal illness with a life expectancy of less than one year.

 Evidence of systemic bacterial or cutaneous infection, including groin infection.

 Evidence of MRSA (Methicillin-resistant Staphylococcus aureus) and/or VRE (vancomycin-resistant Enterococci) colonisation.

 With arterial access other than the common femoral artery.*

 Patients suffering with definitive or potential coagulopathy or platelet count less than 100,000/µl.

 Patient with a haematocrit of less than 32 %.

 A measured activated clotting time (ACT) of greater than 350 seconds immediately prior to sheath removal.*

 If patients are expected to be continuously treated with anticoagulation therapy post-procedure such that their ACT reading is expected to be elevated above 350 seconds for more than 24 hours after the procedure.

 Evidence of arterial diameter stenosis greater than 20 % within 20 mm of the arteriotomy.*

 Circumferential calcification within 20 mm of the arteriotomy.*

 Use of systemic thrombolytic agents within 24 hours prior to or during the catheterisation procedure which cause the concentration of fibrinogen to be less than 100 mg/dl.

 Patients in which the arteriotomy is less than 18 F or greater than 24 F.*

 Known allergy to any of the materials used in the device (Refer to Instructions for Use).

 Currently enrolled in any other investigational clinical study, where the primary endpoint has not yet been achieved.

 Patients judged unsuitable for surgical repair of the access site.

 If puncture site is via a vascular graft.

 If there is any indication that the puncture has been made in the profunda femoris or located less than 10 mm above the profunda femoris.*

 Patients with a common femoral artery lumen diameter of less than 7 mm.

 Patients that have a lower extremity amputation from an access site limb.

 Patients that have undergone a percutaneous procedure using a non-absorbable vascular closure device (excluding suture mediated) for haemostasis in the ipsilateral leg.

 Patients that have undergone a percutaneous procedure greater than 8 F in the ipsilateral leg, within the previous 90 days.

 Patients that have undergone a percutaneous procedure of 8 F or less using an absorbable intravascular closure device for haemostasis, in the ipsilateral leg, within the previous 90 days.

 Patients that have undergone a percutaneous procedure of 8 F or less using a suture mediated closure device for haemostasis, in the ipsilateral leg, within the previous 30 days.

 Patients that have undergone a percutaneous procedure of 8 F or less using manual/mechanical pressure for haemostasis in the ipsilateral leg, within the previous 30 days.

 Patients with an acute haematoma of any size, arteriovenous fistula or Pseudoaneurysm at the access site.*

 Significant blood loss/transfusion during interventional procedure or within 20 days prior to procedure requiring transfusion of greater than 4 units of blood.*

 Angiographic evidence of arterial laceration, dissection or stenosis within the external iliac or femoral artery before the use of the VCD.*

 May not be known until after the patient has given informed consent and the procedure has started.

['Percutaneous Closure of Arteriotomy in Common Femoral Artery']


Homocysteine and Progression of Atherosclerosis

Summary: In the first phase, to establish the relationship of progression of peripheral vascular disease (PVD) to plasma homocysteine. In the second phase, to conduct a randomized, controlled trial of folic acid treatment of plasma homocysteine in peripheral vascular disease.
Inclusion criteria: No eligibility criteria
Exclusion criteria:

['Cardiovascular Diseases', 'Peripheral Vascular Diseases', 'Atherosclerosis', 'Cerebrovascular Disorders', 'Myocardial Infarction', 'Heart Diseases', 'Hyperhomocysteinemia']

Cardiovascular Diseases
Peripheral Vascular Diseases
Atherosclerosis
Cerebrovascular Disorders
Myocardial Infarction
Heart Diseases
Hyperhomocysteinemia


Characterize Patients With Moderately Active Rheumatoid Arthritis (RA)

Summary: To assess the baseline (i.e. RA therapy initiation) characteristics in a real-world setting across two moderate RA cohorts: a Test Group of patients newly exposed to etanercept (Enbrel) therapy and a Control Group of patients with similar disease characteristics newly exposed to other, non-biologic therapies.~To assess the change over time (from baseline to the most recent follow-up) in the characteristics described at baseline in 2 British Society for Rheumatology Biologics Register (BSRBR) cohorts (i.e. moderate RA patients treated with Disease modifying anti-rheumatic drugs (DMARDs) alone versus moderate RA patients treated with Enbrel).
Inclusion criteria: inclusion criteria:

 The Test Group will be patients with rheumatoid arthritis, newly starting therapy with etanercept (Enbrel). inclusion criteria for the exposed cohort subjects are:

 Patients aged 18 years and over at the time of diagnosis;

 Patients from the BSRBR with moderate RA as defined by a DAS28 (>3.2 and ≤5.1);

 Patients who have given informed consent for long term follow-up and access to all medical records;

 Patients initiating (i.e. at leats one treatment) treatment with etanercept (Enbrel) for RA.

 The Control Group:

 Patients aged 18 years and over a the time of diagnosis;

 Patients from the BSRBR with moderate RA as defined by a DAS28 (>3.2 and ≤5.1);

 Patients who have given informed consent for long term follow-up and access to all medical records; Patients are receiving at least one traditional DMARD and have never been prescribed a biologic agent;

Exclusion criteria: :

 Per BSRBR registry since data is retropsectively being analyzed


Enhancing ADHD Driving Performance With Stimulant Medication

Summary: Among children, attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk for accidents, especially bicycle and pedestrian (Leibson 2001; Jensen 1988; DiScala 1998). Anywhere from 40% to 80% of children diagnosed with ADHD continue to display symptoms of the disorder into adolescence(Barkley 1990; Gittelman 1985). Adolescents with ADHD are also at an increased risk for driving-related accidents, being 2 to 4 times more likely to experience a motor vehicle accident (Barkley 1993; Barkley 1996; Cox 2000), 4 times as likely to be at fault in the accident (Barkley 1993), and over 3 times more likely to incur associated injuries as a result of the accident(Murphy 1996).~Stimulant treatment with immediate-release methylphenidate (IR MPH) has been demonstrated to improve driving performance in adolescents with ADHD.~Hypothesis to be Tested:~Main study: Just as stimulant medication improves simulation and on-road driving performance of ADHD teenagers, it is hypothesized that stimulant medication will improve routine driving performance.~Substudy - Extended wear (15 hours) of Daytrana will lead to safer driving late in the evening (22:00 and 01:00), when the most dangerous driving mishaps are most likely to occur, and the next morning at 09:00.
Inclusion criteria: inclusion criteria:

 ADHD diagnosis

 Valid driver's license

 Not taking any medication for their ADHD

 Have access to a car of which they are the primary driver

 Have a history of approximately two driving collisions or citations

 Have a history of responsiveness to methylphenidate

Exclusion criteria: :

 Older than 25 years of age

 Bi-polar disease

 Psychosis

 Satisfy the DSM IV criteria of active depressive or anxiety disorders

 Have any medical condition that might impair driving or be contra-indicated for the use of methylphenidate

 Pregnant or intending to get pregnant for the duration of the study,breastfeeding or intending to breastfeed for the duration of the study

 Have skin allergies or skin condition that could be exacerbated by wearing the medication patch

 Have documented allergy, hypersensitivity, or intolerance to methylphenidate

 Have documented hypersensitivity to the Daytrana® adhesive backing

 Have (history of):

 seizures (except febrile seizure in infancy)

 liver or renal disease

 glaucoma

 chronic skin conditions or contact sensitivities

 current symptoms suggestive of cardiac disease

 cardiovascular disease, e.g.

 structural cardiac abnormalities

 cardiac Arrythmias

 cardiomyopathy

 hypertension

 reported ECG abnormality

 vocal tics, motor tics, Tourettes Disorder or family history of Tourettes

 Have a current diagnosis of

 Psychosis

 Bi-polar disease

 Anxiety disorder

 Substance Use Disorder/Substance Abuse Disorder

 Substudy: In addition to the above requirements, in order to participate in the substudy, participants must be capable of driving the simulator without experiencing simulation sickness

['Attention Deficit Hyperactivity Disorder']


European Clinical Evaluation of the BD HPV Assay on the BD Viper LT System

Summary: The purpose of the study is to compare the results of the Becton Dickinson (BD) Human Papilloma Virus (HPV) Assay on the Viper LT instrument from SurePath media diluted in HPV diluent (pre-quot and/or residual), PreservCyt media diluted in HPV diluent (pre-quot and/or residual) and a BD cervical brush in BD transport medium to reference histology results from biopsy.
Inclusion criteria: inclusion criteria:

 Referred to follow up due to one or more abnormal Pap or an HPV infection

 Subjects who have provided informed consent

 Subjects who meet the minimum age set forth by the ethics committee (EC) and/or national screening guidelines.

Exclusion criteria: :

 Known to be pregnant

 With prior complete or partial hysterectomy involving removal of cervix

 Subjects with an application of chemical compounds to the cervical area 24 hour prior to study entry- this includes acetic acid, iodine, spermicide, douche, anti-fungal meds.

 Subjects on who conization, Loop electrosurgical excision procedure (LEEP), laser surgery or cryosurgery has been performed.