Does Discontinuation of Aspirin Treatment Following Head Trauma Decrease the Incidence of Chronic Subdural Hematoma?

Summary: Anti-aggregation therapy, including treatment with low-dose aspirin (LDA) is an established risk factor for intracranial hemorrhage, including chronic subdural hematoma (CSDH); however evidence guiding the decision to continue or discontinue LDA in patients who have sustained mild head trauma with no sign of injury on CT is lacking. The investigators aim to assess whether continued aspirin treatment increases the risk of CSDH in mild head trauma patients 50 years and older who present with negative head CT. The investigators further aim to use the initial findings to refine the study design, with the goal of performing a larger, multi-institutional study in the future.~Over a 12-month period, approximately 100 patients ≥50 years of age on LDA prophylaxis presenting to Hadassah's Emergency Department after sustaining mild head injury, will be examined by the neurosurgeon on call. Those who have no sign of intracranial hemorrhage at clinical or CT examination, and who meet inclusion / exclusion criteria, will be invited to participate in a randomized study. Informed consent will be obtained. Patients will be remotely randomized for continuation or cessation of LDA treatment. Follow-up CT and clinical examination will be performed 3-5 weeks after trauma.~The two-proportions test will be used to assess whether there is a statistically significant difference in the rate of CSDH in patients randomized to cessation of LDA therapy and those randomized to continuation of LDA. Relationships between the explanatory the dependent variables will be explored with classical parametric and nonparametric statistical methods, including multivariate analysis, logistic regression, the two proportions test, and the independence test. Several measures of association/correlation between pairs of variables will be analyzed as well.~The investigators hypothesize that continuation of LDA will not be associated with increased risk for chronic subdural hematoma, and that cessation of treatment will not be associated with a decrease in chronic subdural hematoma. The investigators further hypothesize that cessation of LDA for this period will not be associated with increased risk for clinically significant cerebrovascular, cardiovascular, thrombotic, of embolic event.
Inclusion criteria: inclusion criteria:

 Completion of informed consent by the patient or a legally appointed guardian

 Age ≥ 50 years

 Sustained mild head trauma with visit to the emergency department of the Hadassah-Hebrew University Medical Center within 24 hours after trauma

 Low-dose aspirin therapy (75-100 mg) at time of head trauma

 Admission non contrast head CT with no evidence of intracranial hemorrhage or skull fracture, as assessed by the neurosurgical resident on call and confirmed by an attending neuroradiologist

Exclusion criteria: :

 Documented or suspected myocardial infarction within the last 12 mo

 Documented or suspected transient ischemic event or cerebrovascular accident within the last 12 months

 Coronary intervention within the last 6 mo

 Vascular stenting or bypass within the last 6 mo

 End-stage renal failure requiring dialysis

 Treatment with aspirin dose other than 75-100 mg

 Concomitant treatment by anti-coagulant or other anti-aggregant (e.g. warfarin, low molecular weight heparin, or clopidogrel)

['discontinuation of aspirin therapy', 'continuation of aspirin therapy']

discontinuation of aspirin therapy
continuation of aspirin therapy

['Head Trauma', 'Traumatic Brain Injury', 'Chronic Subdural Hematoma']

Head Trauma
Traumatic Brain Injury
Chronic Subdural Hematoma


A Pilot Study of Lithium in Progressive Multiple Sclerosis

Summary: The purpose of this study is to determine whether lithium carbonate is safe, well-tolerated, and effective at treating progressive forms of multiple sclerosis.
Inclusion criteria: inclusion criteria:

 Diagnosis of a progressive subtype of multiple sclerosis by revised 2005 McDonald Criteria.

 EDSS of 3.0-6.5

 Ages 30-65

 Must be mentally capable of providing informed consent and following study guidelines.

Exclusion criteria: :

 Relapse or steroid treatment within 1 month of trial entry.

 Any current or previous treatment with mitoxantrone, azathioprine, methotrexate, mycophenolate, cyclophosphamide, or any experimental therapy.

 Women who are pregnant, wishing to become pregnant in the coming 30 months, or are breastfeeding.

 Sexually active women unwilling to use reliable contraception (oral contraceptives, condom, IUD).

 Patients with known kidney dysfunction or creatinine >1.4; known cardiac arrhythmia or significant conduction abnormality on EKG; uncontrolled thyroid disease or TSH >20% above the upper limit of normal; uncontrolled psoriasis, HIV, or any other severe medical condition.

 Patients with a history of unstable psychiatric illness or active severe depression.

 Patients with a history of seizure.

 Concurrent use of any of the following medications: Antipsychotics, diuretics, digoxin, or iodide salts.

 Use of non-steroidal anti-inflammatory drugs (NSAIDs) 5 or more days a week.

 Patients with a history of substance abuse in the past year.

 Patients sensitive to gadolinium, or who are unable to undergo the required number of MRI scans.

 Unable to speak or understand sufficient English to consent or complete study procedures.

 Patients unable or unwilling to provide informed consent.


Management of Initial Bleeding/Spotting Associated With the Levonorgestrel-releasing Intrauterine System (MIRENA)

Summary: The purpose of the study is to investigate if the study drugs (tranexamic acid or mefenamic acid) can control irregular bleeding during the first 3 months of using Mirena. The study drugs tested are tested against placebo (dummy medication not containing any active drug). Treatment period is followed by a one-month period when study drugs are not taken but Mirena use is continued.
Inclusion criteria: inclusion criteria:

 Signed and dated informed consent

 Healthy female subjects requesting contraception

 Age: 18 - 45 years inclusive

 Successful interval insertion of MIRENA

 History of regular cyclic menstrual periods

 Normal or clinically insignificant cervical smear not requiring further follow up

Exclusion criteria: :

 Pregnancy or lactation

 Climacteric symptoms prior to the screening visit

 Known or suspected clinically significant ovarian cysts, endometrial polyps, fibroids, or other genital organ pathology, that, in the opinion of the investigator, may interfere with the assessment of the bleeding profile during the study

 Undiagnosed abnormal genital bleeding

 Current or history of thrombembolic disease, or established risk factors for venous thromboembolism

 Current migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia, or exceptionally severe headaches

 Hypersensitivity to any ingredient of the investigational medicinal products or the non-investigational medicinal product

 Daily or frequent use of a nonsteroidal anti-inflammatory drug (NSAIDs) for any condition

 Not willing to use nonsteroidal anti-inflammatory drug (NSAIDs) medication as pain medication during the double blind treatment period

['Tranexamic acid', 'Mefenamic acid', 'Placebo', 'Mirena (Levonorgestrel IUS, BAY86-5028)']

Tranexamic acid
Mefenamic acid
Placebo
Mirena (Levonorgestrel IUS
BAY86-5028)


OnT4-Thyroglobulin Assay Before rhTSH-Aided Radioiodine Ablation

Summary: Thyroidectomy followed by administration of large activities of 131-iodine (131I) is the treatment of choice for differentiated thyroid carcinoma (DTC). The serum thyroglobulin (Tg) measurement during hypothyroidism (offT4-Tg), just before radioiodine thyroid ablation, has proved to be effective for predicting persistent/recurrent disease. However, the Tg measurement cannot be used as a corresponding value for preablative offT4-Tg when rhTSH is used as stimulous before treatment. The present study was undertaken to evaluate if post-thyroidectomy Tg values, measured before rhTSH-stimulation and radioiodine administration, is of prognostic value in patients affected by DTC. We enrolled 28 patients with DTC and submitted to total thyroidectomy. Thyroxine (T4) treatment was started just after surgery to suppress TSH levels. Six to nine weeks later Tg levels were measured both basally (onT4-Tg) and after rhTSH (rhTSH-Tg) stimulation. Subsequently, T4 was stopped and serum Tg measured (offT4-Tg) just before 3700 MBq of 131I-iodide administration. A post-treatment whole body scan (PT-WBS) was performed and neck radioiodine uptake (RAIU) measured. A significant relationship was found between onT4-Tg and both rhTSH-Tg and offT4-Tg. The onT4-Tg levels of 0.2 ng/mL or higher predicted PT-WBS results with a 100% negative and 43% positive predictive values, respectively. Additionally onT4-Tg levels of 0.9 ng/mL or more predicts 12-months recurrences with 100% negative and 60% positive predictive value. In comparison, 1.0 ng/mL or higher offT4-Tg values predicted PT-WBS results and 12-months restaging with 94% and 100% negative and 45% and 27% positive predictive value, respectively. Basing on our data we conclude that preablative onT4-Tg may be of value as prognostic marker when rhTSH-aided radioiodine ablation is done. Additionally, the role of preblative onT4-Tg measurement as a yard-stick for radioiodine ablation should be further evaluate.
Inclusion criteria: inclusion criteria:

 Hiostologically proved DTC (M0)

Exclusion criteria: :

 Preoperative metastasis


Summary: The Women's Health Initiative Study of Cognitive Aging (WHISCA) is a two-armed, randomized, placebo controlled, clinical trial designed to assess the efficacy of postmenopausal hormone therapy (HT) on age related changes in specific cognitive functions.
Inclusion criteria: inclusion criteria:

 Enrolled in WHIMS

 At least 65 years old

 Not diagnosed with dementia

Exclusion criteria: :

 Women younger than 65 years of age

 Have dementia

 not enrolled in WHIMS


Left Atrial Distensibility to Predict Left Ventricular Filling Pressure and Prognosis in Patients With Severe Mitral Regurgitation

Summary: A large left atrial (LA) volume, which represents chronic diastolic dysfunction, is associated with a poor outcome, regardless of systolic function. Thus, the LA volume provides a long-term view of whether the patient has diastolic dysfunction, regardless of the loading conditions present at the examination, such as hemoglobin A1c in diabetes mellitus. To date, the relation between the LA volume and left ventricular (LV) filling pressure has not been confirmed directly by simultaneous echocardiographic catheterization. The present study, therefore, assessed the correlation between the LA volume and LV filling pressure in patients with severe mitral regurgitation (MR). Because the LA pressure increases to maintain adequate LV diastolic filling, increased atrial wall tension tends to dilate the chamber and stretch the atrial myocardium. Therefore, the lower the ability of the left atrium to stretch, the greater the pressure in the left atrium. The study is designed to assess 1) the relationship between LV filling pressure and LA distensibility, and 2) the power of left atrial distensibility to predict the prognosis, including operation mortality, the rate of post-operation atrial fibrillation, and late heart failure event in patients with severe mitral regurgitation.
Inclusion criteria: inclusion criteria:

 Patients with severe mitral regurgitation are admitted for surgical intervention and are willing to participate in this study.

Exclusion criteria: :

 Presence of mitral stenosis

 More than mild severity of aortic valvular problem

 Any abnormality of atrial septum (e.g., atrial septal defect or aneurysm)

 Rhythm other than sinus rhythm

 Inadequate image quality

 Lack of informed consent

['Mitral Valve Insufficiency', 'Atrial Fibrillation', 'Heart Failure']

Mitral Valve Insufficiency
Atrial Fibrillation
Heart Failure


Transfusion Effects in Myelodysplastic Patients: Limiting Exposure

Summary: The goal of this study was to compare a restrictive RBC transfusion policy (a Hb transfusion trigger: 7.2 gr/dl) with a more liberal RBC transfusion policy (a Hb transfusion trigger: 9.6 gr/dl) on physical fatigue.
Inclusion criteria: inclusion criteria:

 diagnosis myelodysplastic syndrome (primary or secondary) based on cytopenia in at least 1 cell line + dysplasia in 2 cell lines (and no other cause (especially deficiencies)) and a pathologic anatomic diagnosis after bone marrow punction.

 refractory anaemia (RA): blood: ≤ 1% blasts, ≤ 1 x 109 monocytes; bone marrow: < 5% blasts, ringed sideroblasts ≤ 15% of the erythroid cells

 refractory anaemia with ringed sideroblasts (RARS): blood: ≤ 1% blasts, ≤ 1 x 109 monocytes; bone marrow: < 5% blasts, ringed sideroblasts > 15% of the erythroid cells

 refractory anaemia with excess blasts (RAEB): blood: < 5% blasts, ≤ 1 x 109 monocytes; bone marrow: blasts ≥ 5 -≤ 20%

 chronic myelomonocytic leukaemia (CMML): blood: >1 x 109/l monocytes, <5% blasts; bone marrow: blasts < 20%, increase of the monocytic component

 erythrocyte transfusion need

 working knowledge of the national language

 written consent for participating this study (informed consent)

Exclusion criteria: :

 candidate for bone marrow- or organ transplantation

 medication: growth factors (GM-CSF), or EPO

 patients who will receive an intensive chemotherapeutic treatment with a cytopenia, expected longer than 2 weeks

 refractory anaemia with excess blasts in transformation (RAEB-t): blood: ≥ 5% blasts or Auer rods; bone marrow: or blasts > 20 - < 30% or Auer rods

 pregnancy at the moment of inclusion

 patients with congenital severe haemolytic anaemia, like thalassemia or sickle cell anaemia

 patients with AIDS or a severe congenital or acquired (e.g. iatrogenic) immunological disorder

 severe active infections at the moment of inclusion

 severe cardiac, pulmonal, neurological, metabolic or psychiatric disease at the moment of inclusion


The Signal-averaged ElectrocArdiogram in Long Term Follow-up of Chronic CHagas Disease - RIO de Janeiro Cohort

Summary: The study investigated 100 subjects, both genders, with chronic Chagas disease, confirmed by at least two distinct serological tests, and classified according to Los Andes classification in a long term follow-up aiming at identifying the predictive value of the signal-averaged electrocardiogram for cardiac death and ventricular tachycardia.~All subjects admitted to the study were submitted to clinical history taking, physical examination, and noninvasive assessment, including blood pressure measurement, resting 12-lead surface electrocardiogram, 24h ambulatory electrocardiogram monitoring, M-Mode/two-dimensional echocardiogram, signal-averaged electrocardiogram in both time and frequency domains. Selected subjects were further submitted to treadmill stress test and coronary angiography to rule out coronary heart disease.~Subjects were followed by non-investigational primary care assistance at three to six months scheduled clinical visits on an outpatients basis. Both noninvasive and invasive evaluation during follow-up were requested at discretion of primary evaluation. Adverse outcomes were ascertained by review of medical records and active contact to either study subjects or their relatives.
Inclusion criteria: inclusion criteria:

 Clinically stable outpatients with at least 10 years of regular outpatients follow-up and positive epidemiological history and serological confirmation of Chagas disease with ate least two immunological tests

Exclusion criteria: :

 Any degree of atrioventricular block or non-sinus rhythm

 Previous documented acute coronary events (due to documented obstructive epicardial coronary vessels)

 Chronic obstructive pulmonary disease

 Rheumatic valvular heart disease

 Alcohol addiction

 Thyroid dysfunction

 Abnormal serum electrolytes and biochemical abnormalities

['Cardiac Arrhythmia', 'Stroke', 'Left Ventricular Function Systolic Dysfunction', 'Cardiac Death', 'Chagas Cardiomyopathy']


Cryotherapy in Treating Patients With Primary Lung Cancer or Lung Metastases That Cannot Be Removed By Surgery

Summary: RATIONALE: Cryotherapy kills tumor cells by freezing them. This may be an effective treatment for primary lung cancer or lung metastases that cannot be removed by surgery.~PURPOSE: This clinical trial is studying how well cryotherapy works in treating patients with primary lung cancer or lung metastases that cannot be removed by surgery.
Inclusion criteria: DISEASE CHARACTERISTICS:

 Histologically or cytologically confirmed malignant pulmonary neoplasm

 New lung lesion(s) with definitive clinical and imaging features of primary or metastatic disease allowed

 Imaging findings compatible with localized treatment failure after prior cryotherapy allowed

 Malignant pleural effusion allowed provided it is associated with a distinct measurable pulmonary mass amenable to cryotherapy

 Metastatic disease must meet all of the following criteria:

 Primary tumors have been resected or have been deemed controlled by other therapies

 No other widespread metastases evident (e.g., multiple hepatic or brain metastases)

 Each pulmonary mass must be amenable to CT-guided percutaneous cryotherapy approach

 No more than 5 targeted masses for study therapy

 Target mass defined as pulmonary, hilar, mediastinal, and/or chest wall mass > 1 cm, but < 10 cm in average diameter

 Unresectable disease by surgical consultation OR patient refused surgical options

 Nonenhanced and enhanced CT scan required within the past 6 weeks done at 4-5 mm increments with available soft tissue and mediastinal windows to assess size and extent of all thoracic tumors

 PET scan required within the past 6 months noting the correlation with the above CT locations, if not already obtained by a combined PET/CT scanner

 PATIENT CHARACTERISTICS:

 Karnofsky performance status (PS) > 60-100% OR WHO/ECOG/Zubrod PS 0-2

 FEV_1 > 30% of predicted

 DLCO > 40% of predicted

 Platelet count ≥ 70,000/mm^3

 INR < 1.5

 No uncontrolled coagulopathy or bleeding diathesis

 Not pregnant or nursing

 Negative pregnancy test

 No serious medical illness, including any of the following:

 Uncontrolled congestive heart failure

 Uncontrolled angina

 Myocardial infarction

 Cerebrovascular event within 6 months prior to study entry

 No medical contraindication or potential problem that would preclude study compliance

 PRIOR CONCURRENT THERAPY:

 At least 7 days since prior aspirin and aspirin-like medications

 At least 3 days since prior warfarin, clopidogrel bisulfate, or similar compounds

 No concurrent drugs causing bleeding tendencies (e.g., aspirin, warfarin, or clopidogrel bisulfate)

 No concurrent participation in other experimental studies
Exclusion criteria:

['cryosurgery', 'positron emission tomography']

cryosurgery
positron emission tomography


Partnering With Media and Vaccination Program to Improve Infant and Young Child Feeding

Summary: Infant and young child feeding (IYCF) is a key determinant of under-nutrition and overweight in young children. In Mexico, breastfeeding extends well into the second half of infancy, but animal-source foods, cereals, and legumes are not regularly provided to the child by 9 mo. This study evaluates whether knowledge and practices about dietary diversity and food consistency can be improved using a two-component intervention strategy in semi-urban communities in Mexico. The two components will deliver appropriate complementary feeding messages using: (a) nurses during the 1st National Vaccination Week (NVW); and (b) radio messages and interviews. The intervention is evaluated using a cluster randomized design in small semi-urban communities in two states in Mexico with pre- and post-test questionnaires designed to assess changes in feeding behaviors.
Inclusion criteria: inclusion criteria:

 Mothers with healthy children between 6 and 24 mo

Exclusion criteria: :

 None

['Appropriate complementary feeding messages']


Comparison Between Natural and Artificial Cycle in Recipient Oocyte Patients

Summary: The purpose of this study is to compare the natural cycle (without any medication) with the well-established artificial cycle in an egg donation program.
Inclusion criteria: inclusion criteria:

 infertile females with preserved gonadal function

 ages 18 - 44 years old included

 first oocyte donation cycle

Exclusion criteria: :

 BMI: > 28

 recurrent miscarriages (3 or more)

 recurrent of implantation failure

 severe male factor

 important miomas

 > 44 years old

 Problems with the drugs used in the study

['observation natural cycle', 'Agonist GnRH; estradiol Valerate; progesterone']


The Blood Saving Effect of Tranexamic Acid in Total Knee Arthroplasty With Rivaroxaban as Thromboprophylaxis

Summary: The aim of this study was to conduct a prospective, randomized, double-blind study and assess the efficacy of and safety for thromboprophylaxis of rivaroxaban in total knee arthroplasty patients when tranexamic acid is used for bleeding prophylaxis.
Inclusion criteria: inclusion criteria:

 End-stage arthritis of the knee

 Failure of medical treatment or rehabilitation

 Hemoglobin > 10g/dl

 No use of non-steroid anti-inflammatory agent one week before operation

Exclusion criteria: :

 Preoperative Hemoglobin ≦10 g/dl

 History of infection or intraarticular fracture of the affective knee

 Renal function deficiency (GFR < 55 ml/min/1.73m2)which is relative contraindicated for venography

 Elevated liver enzyme, history of liver cirrhosis, impaired liver function and coagulopathy (including long-term use anticoagulant)

 History of deep vein thrombosis, ischemic heart disease or stroke

['Tranexamic Acid 5%,5ml/amp (intraoperative)', 'Tranexamic Acid 5%,5ml/amp (3 hours after operation)', '0.9% Normal Saline (intraoperative)', '0.9% Normal Saline (3 hours after operation)', 'rivaroxaban (10mg)']


A Study of Stress Heart Imaging in Patients With Diabetes at Risk for Coronary Disease.

Summary: The study is designed to see if stress heart imaging can be used as a screening exam in patients with diabetes and risk factors of developing of coronary artery disease and experiencing future cardiac events.
Inclusion criteria: inclusion criteria:

 History of diabetes for at least 5 years, with a least 2 risk factors (i.e. hypertension, elevated cholesterol levels, history of or current smoker, obese, family history of heart disease) & atypical chest pain.

Exclusion criteria: :

 Typical chest pain being treated with medication, unable to exercise, previous confirmed heart disease


Comparing Therapeutic Hypothermia Using External and Internal Cooling for Post-Cardiac Arrest Patients

Summary: Controlled therapeutic hypothermia is a method of preserving neurological function post-resuscitation.It has been associated with improved functional recovery and reduced histological deficits in animal models of cardiac arrest.
Inclusion criteria: inclusion criteria:

 Sustained return of spontaneous circulation (ROSC) after cardiac arrest, for more than 30 min

 Patients aged between 18 to 80 years.

 Patients who are hemodynamically stable, with a systolic BP > 90 mmHg with or without inotropic support.

 Patients comatose or unresponsive post-resuscitation

Exclusion criteria: :

 Hypotension despite fluid and/or vasopressor support

 Positive pregnancy test in women below 50 years

 Premorbid status bedbound and uncommunicative

['Internal Cooling', 'External Cooling']


Effect of Hormone Replacement Therapy on Lupus Activity

Summary: Hypothesis, HRT does not increase the risk of lupus activity exacerbation, it is effective for the relief of menopausal symptoms and improves bone mineral density.~Double-blind, randomized, placebo controlled clinical trial.~Objectives~Determine the effect of HRT on disease activity, menopausal symptoms, bone mineral density, lipid profile, and mammographic parenchymal density in menopausal women with SLE.~Determine the incidence rate of major side effects of HRT in menopausal women with SLE.~Outcome Measures~Primary outcome will be global disease activity throughout the follow-up period.~Incidence of lupus flares, time to the first flare, changes in SLEDAI values from baseline at each follow-up visit, maximum disease activity, lupus treatment, hospitalizations, thromboses, and deaths.~Menopausal symptoms and depression will be assessed utilizing the Greene Climacteric Scale questionnaire and the Beck Depression Inventory.~Bone mineral density of lumbar spine and hip will be performed with dual energy x-ray absorptiometry. In addition, blood and urine samples to measure biochemical markers of bone turnover.~Estradiol levels, lipid profile,coagulation tests, cervical cytology examinations, mammography.~Inclusion Criteria: (Any two of the following criteria)~Amenorrhea of 6 months or more~Serum FSH level of 30 IU/L or more~Menopausal symptoms~Age 48 years or older.~Exclusion Criteria:~Women older than 65 years~Severe lupus activity at baseline~Use of estrogens within 3 months of the screening visit~Serum creatinine of 2.0 mg/dL or more~Hypertriglyceridemia 500 mg/dL or more~Metabolic bone diseases~Liver disease~Untreated hyperthyroidism~Recent thrombosis~Malignancy~Endometrial hyperplasia~Undiagnosed uterine bleeding~Cervical dysplasia.~Subject allocation Random assign, using a computer-generated randomization list to: Conjugated equine estrogens 0.625 mg/day plus 5 mg/day of medroxyprogesterone acetate p.o. for the first 10 days per-month, or biologically inert placebo.All women will receive 1200 mg of calcium carbonate and 800 IU of vitamin D, daily.~Follow-up procedure All patients will be evaluated by a rheumatologist and a reproductive health specialist at baseline,1,2,3,6,9,12,15,18,21, and 24 months.~Rheumatic evaluation:~General information (baseline).~Lupus activity (every visit).~Medications: (every visit)~Gynecological evaluation:~Onset of symptoms since the previous visit using a standardized questionnaire. In addition, a gynecological examination will be performed.~Criteria for early termination of the study:~A patient will be discontinued from the study whenever any of the following criteria would be present:~Development of severe lupus activity (SLEDAI > 30).~Development of any putative complication to hormone therapy.~Development of any other severe complications due neither to SLE nor hormone therapy.~Need prolonged immobilization.~Statistical analysis:~Between-group comparisons of lupus activity, maximum SLEDAI, and change in SLEDAI score from baseline at each follow-up visit. Incidence-density rates of flares with relative risk and 95 percent confidence intervals.Probability of flares throughout the study using life-table analyses and log-rank test.~Climacteric symptoms as the mean value of the Green's scale score at baseline and at each follow-up visit, between-group and intra-group. Bone mineral density as the mean value at baseline, 12 and 24 months, between and intra-group.~The proportion of patients in each group who develop secondary effects, as well as the number who quit the study during the follow-up period.~Continuous variables will be compared using Student's t-test, and categorical variables using chi-square or Fisher's exact test. Within-group comparisons will be done using the Wilcoxon signed-rank test. P values will be two-sided. Analyses will be conducted by the intention-to-treat method.
Inclusion criteria: inclusion criteria:

 Eligible women will be those having any two of the following criteria

 Amenorrhea of 6 months or more.

 Serum follicle-stimulating hormone level of 30 IU/L or more.

 Menopausal symptoms.

 Age 48 years or older.

Exclusion criteria: :

 Women older than 65 years.

 Severe lupus activity at baseline (SLEDAI score, more than 30).

 Use of estrogens within 3 months of the screening visit.

 Serum creatinine of 2.0 mg/dL or more.

 Hypertriglyceridemia 500 mg/dL or more.

 Metabolic bone diseases.

 Liver disease.

 Untreated hyperthyroidism.

 Recent thrombosis.

 Malignancy.

 Endometrial hyperplasia.

 Undiagnosed uterine bleeding or cervical dysplasia

['Conjugated equine estrogens 0.625 mg/d + MPA 5 mg/d/10d']


Phase II Study of Pandemic Influenza Vaccine

Summary: The World Health Organisation has warned that an influenza pandemic is inevitable. The avian influenza H5N1 virus strain is the leading candidate to cause the next influenza pandemic. This study will test the safety and immunogenicity of a H5N1 Pandemic Influenza Vaccine in healthy adults. The Study will also assess Lot to Lot consistency of the Pandemic Influenza Vaccine.
Inclusion criteria: inclusion criteria:

 Healthy Adults

Exclusion criteria: :

 Previous vaccination with an influenza Vaccine containing the H5N1 strain

 History of clinically significant medical conditions

 History of Guillian-Barre Syndrome or active Neurological disease


Magnesium Sulfate During the Postpartum in Women With Severe Preeclampsia

Summary: There is no evidence that patients receiving magnesium sulfate before birth are required to maintain the drug for 24 hours. Therefore the investigators will have a randomized clinical study in patients with severe preeclampsia who have been treated with impregnation of magnesium sulphate and at least eight hours have received the drug before birth. If the patient agrees and signs the consent is randomized to: 1-receive sulfate for 24 hours postpartum as usual or, 2- not receiving the postpartum magnesium sulfate or other anticonvulsant drugs. This study can be conducted in 12 maternity latin america.
Inclusion criteria: inclusion criteria:

 Severe preeclampsia or severe preeclampsia aggregated to chronic hypertension with > 24 weeks of gestation treated with 4-6 grams of magnesium sulfate for impregnation with a minimum of 8 hours continuous of magnesium sulfate before delivery

 The study begins to terminate pregnancy

Exclusion criteria: :

 HELLP syndrome

 Eclampsia

 Renal insufficiency

 Diabetes mellitus

 Disease of collagen

 Heart disease


Clinical Study of Recombinant Mycobacterium Tuberculosis ESAT6-CFP10 Allergen

Summary: 720 cases TB (Tuberculosis patients) participants、360 cases non-TB participants with lung disease and suspected TB patients who all meet the standard are divided into different groups through a randomized and blind method. Every subject inject intradermally ESAT6-CFP10 and TB-PPD (tuberculin purified protein derivative) in different arms of the same person by blind method. Specific gama-interferon (γ-IFN) detection is needed before the injection.Measure the induration and (or) redness of longitudinal diameter size and transverse diameter vernier caliper by vernier caliper after injection 24h, 48h and 72h. At the same time, we observe all kind of adverse events.
Inclusion criteria: inclusion criteria of TB (tuberculosis:include pulmonary tuberculosis and extra pulmonary tuberculosis) subjects:

 judge the pulmonary tuberculosis patient according to Health industry standard of the People's Republic of China WS288-2008:Diagnostic Criteria for pulmonary tuberculosis;

 18 to 65 years old ,no gender limited;

 Consent and signed informed consent forms (ICF);

 Comply with follow-up.

 inclusion criteria of extra pulmonary tuberculosis subjects:

 Diagnosed extra pulmonary tuberculosis by epidemiology, imaging, clinical symptoms, pathological examination and so on;

 Lesions outside the lungs;

 be in unfinished reinforced phase by chemotherapy;

Exclusion criteria:  of TB (tuberculosis) subjects:

 Accompanied by the following severe illness:advanced cancer, diabetes, copd in acute episodes, acute/progressive liver disease or kidney disease, congestive heart failure, ect;

 Taking part in other clinical or within three months involved in any other clinical;

 Severe allergic constitution:allergic to two or more drugs;

 in pregnancy or lactation;

 in a mental illness;

 Any conditions affect the trial evaluation by investigator's judgement.

 inclusion criteria of non-TB participants with lung disease:

 A clear lung disease but can exclude pulmonary tuberculosis by clinical symptoms, imaging, laboratory examination.

 18 to 65 years old, no gender limited;

 Consent and signed informed consent forms (ICF);

 Comply with follow-up.

['ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm', 'ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm']


Effect of Osteopathic Manipulative Medicine on Motor Function and Quality of Life in Cervical Dystonia

Summary: The purpose of the proposed research is to determine if Osteopathic manipulative medicine (OMM) used alone or in combination with the standard treatment of botulinum toxin intramuscular injections improves motor function and quality of life amongst people with cervical (neck) dystonia.
Inclusion criteria: inclusion criteria:

 clinical diagnosis of cervical dystonia or spasmodic torticollis

 ages 2-100

Exclusion criteria: :

 no clinical diagnosis of cervical dystonia or spasmodic torticollis

 symptoms beginning over the age of 40

 pregnant women are excluded from Aim 2


A Study on the Mechanism of Cough Hypersensitivity

Summary: The aim of this study is described as follows,~To establish a validated method to test cough reflex sensitivity conducted by transient receptor potential vanilloid 1(TRPV1).~To observe the variance of cough reflex sensitivity conducted by transient receptor potential ankyrin 1(TRPA1) of chronic patients and the relationship between cough reflex sensitivity conducted by TRPA1 and conducted by TRPV1.~To study the distribution of TRPA1 and TRPV1 channels and their relationship to cough reflex sensitivity.
Inclusion criteria: inclusion criteria:

 chronic cough group:

 cough lasting ≥ 8 weeks,characterized by irritating dry cough.

 sensitive to fumes，dust,the odorous and cold air.

 with normal chest x-rays. 4.17-70 years old.

 5.without smoking history. healty controls group: 1.17-70 years old. 2.without smoking hitory or stop smoking for more than 2 years. 3.without chronic cough. 4.without chronic respiratory diseases. 5.without chronic heart, liver, kidney,and autoimmune disease. 6.with normal chest x-rays. 7.with normal pulmonary ventilation function,and histamine challenge test showed negative result.

Exclusion criteria: :

 chronic cough group and healty controls group:

 with respiratory tract infection within 8 weeks.

 with chronic respiratory diseases or severe heart, liver, kidney,and autoimmune disease.

 using Angiotensin-Converting Enzyme Inhibitors(ACEI),bronchodilators,glucocorticosteroid,antihistaminics within one week.

 women during pregnancy or lactation.

 patients with malignant tumours.


Thyroid Treatment Trial

Summary: This project will compare the efficacy and safety of 2 methods of disease modification in the treatment of active moderate and severe thyroid orbitopathy. A prospective, randomized, double-blind, parallel, controlled multidisciplinary clinical trial involving Singapore National Eye Centre, National University Hospital, Changi General Hospital, Tan Tock Seng Hospital and University of British Columbia Orbital Services, Singapore Eye Research Institute, Singapore General Hospital Endocrinology and Radiology Departments and Tan Tock Seng Hospital Rheumatology Department is planned. The SingHealth-SGH High Field MR Research Laboratory will be involved in the MR imaging of the trial patients.~Patients who satisfy the inclusion and exclusion criteria will be asked to participate in this trial. After informed consent (Appendix B) is obtained, each patient will be randomized into one of two treatment arms: 1) Intravenous high-dose pulsed methylprednisolone (1 gram infusion over 1 hour per day with a total of 3 doses over 3 days; 4 cycles at 6 weekly intervals) and oral placebo and 2) Intravenous high-dose pulsed methylprednisolone (same dose) plus oral methotrexate 7.5 mg per week for 2 weeks, increased to 10 mg per week for another 2 weeks then 12.5 mg per week for 5 months (total 6 months of methotrexate treatment). Depending on patient response, the dose can be further increased by 2.5mg per week every 4 weeks to a maximum of 20 mg per week. A strict management protocol will be observed for each recruited patient. Patients who develop adverse side effects or need for surgical intervention will receive appropriate treatment (i.e. treatment will deviate from the protocol but will continue to be monitored). Patients who refuse treatment will be observed clinically and with imaging as a natural control group until such time as intervention is accepted.~The patients will have a baseline assessment followed by regular visits to assess treatment response and adverse effects. Observations will include the use of an inflammatory index, motility measurements including quantitative ductions, exophthalmometry readings, palpebral aperture readings and indices of optic nerve function. With regards to the imaging, the patients will be assessed with an initial quantitative CT scan and 3-Tesla MRI scan prior to treatment. After treatment is started, patients will also undergo repeat MRI scan at 24 weeks and 72 weeks to assess quantitative changes with treatment using the Muscle Diameter Index (MDI) and Pixel Value Ratio (PVR) for the inferior rectus, superior rectus, the medial rectus, lateral rectus and orbital fat (Appendix E). Serum and urine will be obtained at the same time intervals as the MRI scan to assess levels of thyroid hormones, thyroid antibodies and urinary glycosaminoglycans (GAGs). Free T4, free T3 and TSH will be recorded to monitor control of hyperthyroidism. Thyroid antibodies measured will include thyroid stimulating immunoglobulin (TSI), thyrotropin-binding inhibition antibody (TB II), thyroid peroxidase antibodies and thyroglobulin antibody. Other tests including the full blood count, urea and electrolytes will be run prior to each dose of steroid treatment and during follow-up to monitor for adverse effects.~The results of the assessments will be analyzed for significant differences in treatment response between the 2 groups. The indices of interest will include the percentage of patients in each group who demonstrate a decrease in the inflammatory index of at least 2 points and the time taken for 50% of patients to show such a decrease. Other parameters that reflect the visual function and motility will be compared at different points in time after starting treatment to observe response and sustainability of response. From the serial MRI scans, quantitative analysis of orbital tissues will be done to identify changes with treatment. Antibody and GAG levels will be analyzed to detect any change with treatment. The types and frequency of adverse side effects in the 2 groups will also be assessed.~80 normal subjects will be recruited for MRI scan of the orbits and brain to obtain normative values for the MDI and PVR for the Asian population (Appendix E). This will include 20 subjects from each of 4 decades (21-30 years, 31-40 years, 41-50 years, 51-60 years).~The normative data will also be used to create a virtual orbital atlas. This aspect of the study will be performed in collaboration with the Labs for Information Technology (A-Star).
Inclusion criteria: inclusion criteria:

 Confirmed TED (as defined by Bartley and Gorman19)

 - Eyelid retraction (upper eyelid margin at or above the superior corneoscleral limbus in primary gaze without frontalis muscle contraction) in association with any one of the following:

 Thyroid dysfunction or abnormal regulation (increased serum thyroxine or triiodothyronine level, decreased serum thyroid stimulating hormone level, absence of thyroid radioiodine uptake suppression after administration of triiodothyronine, or the presence of thyroid stimulating immunoglobulins in serum)

 Exophthalmos (Hertel measurement of at least 20mm)

 Extraocular muscle involvement (restrictive myopathy or objective evidence of enlarged muscles)

 Optic nerve dysfunction (abnormal visual acuity, colour vision, pupillary reaction or perimetry not attributable to other causes)

 OR

 - Thyroid dysfunction or abnormal regulation in association with any one of the following:

 -Exophthalmos

 - Extraocular muscle involvement

 - Optic nerve dysfunction

 Active disease

 Inflammatory Index

 Inflammatory Index

 Soft tissue feature Rating Chemosis 0 Absent

 Moderate (up to lid margin)

 Severe (over lid margin; persists on closing eye)

 Conjunctival injection 0 Absent 1 Present

 Lid injection 0 Absent

 1 Present

 Lid edema 0 Absent

 Moderate

 Severe (festoons, overhang)

 Pain at rest (clearly defined as retrobulbar aching) 0 Absent 1 Present

 Pain on movement 0 Absent

 1 Present

 Total possible 8

 Active disease is defined as an inflammatory index of at least 3 together with acute or subacute onset (3 months and under) and/or evidence of progression (from history or clinical observation).

 (3) Moderate or severe disease

 Primary Criteria

 Mild Moderate Severe Inflammatory Index <3 3-5 >5

 Motility <1/3 1/3 to 2/3 >2/3 (involving any one muscle) limitation limitation Limitation

 Elevation, depression, adduction and abduction of the individual eyes will be measured with a modified Aimarck perimeter with input from both patient and the orthoptist who performs the test 20.

 Secondary Criteria 21,22,23,24

 Mild Moderate Severe Exophthalmos (mm) <21 21-24 25 or more

 Best corrected vision (Logmar) - - 0.6 or worse

 CT criterion (Muscle Diameter Index) 21-24 25-30 31 and above

 These criteria are not considered absolutes and emphasize measurable indices based on previous studies.

 The presence of at least 1 primary criterion and at least 1 secondary criterion places the patient in the more advanced disease group (in the situation where 1 primary criterion is mild and the other severe, the presence of 1 severe secondary criterion will yield a severe grade whereas absence of this criterion will result in a mild grade) eg 1) a patient with an inflammatory index of 6 and moderate limitation of extraocular motility, 21mm proptosis, 0.3 vision and MDI of 26 has moderate disease as the secondary criteria for severe disease was not present eg 2) a patient with an inflammatory index of 5 and mild limitation of extraocular motility, 21mm proptosis, 0.3 vision and MDI of 30 has moderate disease as 1 primary and 2 secondary criteria for moderate disease were present eg 3) a patient with inflammatory index of 6 and mild limitation of extraocular motility, 20mm proptosis, 0.3 vision and MDI of 21 has mild disease as the secondary criterion for severe disease was absent and the other primary parameter (motility) was graded mild.

 (4) Age between 21 - 60

 (5) Written informed consent is obtained

Exclusion criteria: :

 Previous treatment for TED

 Oral steroids (e.g. immunosuppressive dose) for last 3 months, radiotherapy

 Intravenous pulsed steroid or methrotrexate therapy

 Medically unfit to receive I/V high-dose pulsed methylprednisolone or methotrexate

 History of cardiac arrthymias, recent acute myocardial infarction

 History of seizure

 History of acute bleeding peptic ulcer

 History of pulmonary tuberculosis, Hepatitis B carrier, Hepatitis C positivity, HIV

 Uncontrolled diabetes or hypertension (to be eligible for the trial, random blood glucose must be < 11.1 mmol/L and blood pressure must be 140/90 or lower#. If above these limits, patients can be treated and reviewed at 2 weeks for enrolment when criteria are met - provided the patient does not have optic neuropathy)

 Hepatic dysfunction (Alb, AST, ALT and Alkaline phosphates levels must be within normal range for eligibility)

 Renal impairment (Urea and Creatinine levels must be within normal range)

 Abnormal blood count (outside normal range)

 Others

 Fertile females considering becoming pregnant during the course of the study and those not willing to take precautions to avoid pregnancy

 Both female and male planning to start a family during the trial period or within 6 months of stopping the drugs

 History of seizure

 History of mental / psychiatric disorder

 Patients with clinical features of optic nerve disc pallor at primary presentation will be excluded

['Intravenous Methylprednisolone + Oral Methotrexate vs Intravenous Methylprednisolone + Placebo']


Rule Out Myocardial Infarction by Computer Assisted Tomography

Summary: The goal of this research is to determine noninvasively whether detection of coronary stenosis and plaque by multidetector computed tomography (MDCT) in patients with acute chest pain suspected of acute coronary syndrome (ACS) enhances triage, reduces cost and is cost effective. Among the 5.6 million patients with ACP presenting annually in emergency departments (ED) in the United States, a subgroup of two million patients is hospitalized despite normal initial cardiac biomarker tests and electrocardiogram (ECG). This subgroup is at low (20%) risk for ACS during the index hospitalization. Most (80-94%) patients with a diagnosis of ACS have a significant epicardial coronary artery stenosis ( >50% luminal narrowing). However, in -10% of patients non-stenotic coronary plaque triggers events, i.e. vasospasms, leading to myocardial ischemia. Since the absence of plaque excludes a coronary cause of chest pain, these patients could in theory be discharged earlier reducing unnecessary hospital admissions. Recent publications demonstrate high sensitivity and specificity of MDCT for the detection of significant coronary stenosis compared with coronary angiography and the detection of coronary plaque as validated with intravascular ultrasound. Using 64- slice MDCT we propose to study 400 patients with ACP, negative initial cardiac biomarkers and non-diagnostic ECG. We will analyze MDCT images for the presence of significant coronary artery stenosis and plaque and correlate the data with the clinical diagnosis of ACS (AHA guidelines) during the index hospitalization to determine the sensitivity and specificity. MDCT data, risk factors, and the results of standard diagnostic tests available at the time of MDCT will be used to generate a multivariate prediction function and derive a clinical decision rule. Based on this decision rule we will compare the diagnostic accuracies and cost effectiveness of competing strategies. We hypothesize that an MDCT- based diagnostic strategy will reduce the time to diagnosis of ACS, number of hospitalizations, and absolute cost of management of patients with acute chest pain compared to standard clinical care and is cost effective.
Inclusion criteria: inclusion criteria:

 Patients with any episode > five minutes of chest pain being admitted to rule out acute coronary syndrome

Exclusion criteria: :

 Positive initial troponin or CK-MB tests

 Diagnostic ECG changes (ST- segment elevation or horizontal ST- segment depression in more than two contiguous leads)

 Unstable clinical condition (hemodynamically unstable, ventricular tachycardia, persistent chest pain despite adequate therapy)

 Creatinine Clearance <50 mL/min

 Known allergy to iodinated contrast agents

 Patients on metformin therapy unable or unwilling to discontinue therapy for 48 hours after CT scan procedure

 Known asthma, reactive airway disease

 Patients currently in atrial fibrillation

 Previous intolerance to beta blocker

 Patients that are referred for coronary angiography/PCI by their PCP or cardiologist.

['Acute Coronary Syndrome', 'Myocardial Infarction', 'Unstable Angina Pectoris']

Acute Coronary Syndrome
Myocardial Infarction
Unstable Angina Pectoris


Pediatric Asthma Alert Intervention for Minority Children With Asthma

Summary: Young inner-city children with asthma have the highest emergency department (ED) visit rates. Relying on the emergency department for asthma care can be a dangerous sign of poorly controlled asthma. This research will focus on whether having a specialized asthma nurse join the family at a child's doctor visit after an ED visit for asthma to make sure the child and parent keep the follow-up appointment and have the nurse remind the child's doctor to prescribe preventive asthma medicines and an asthma action plan for home (PAAL intervention) will result in young children with asthma having fewer days with wheezing and cough.~The investigators hypothesize that:~Significantly more children receiving the PAAL intervention will attend greater than 2 non-urgent visits and greater than 6 refills for the child's anti-inflammatory medications over 12 months when compared to children in the control or standard asthma education group.~Children in the PAAL intervention group will experience less morbidity and caregivers will experience increased quality of life compared to children in the control of standard asthma education group.
Inclusion criteria: inclusion criteria:

 All 6 criteria must be met:

 Physician-diagnosed asthma (based on caregiver report with validation from the child's physician)

 > 2 ED visits or > 1 hospitalization for asthma within past 12 months

 Mild persistent to severe persistent asthma based on NHLBI guidelines criteria (7-9) having any 1 of the following:

 An average of > 2 days per week of asthma symptoms

 > 2 days per week with rescue medication use (albuterol, xopenex) OR

 > 2 days per month of nighttime symptoms

 Age > 3 and < 10 years

 Reside in Baltimore Metropolitan area

 Not currently participating in another asthma study or sibling enrolled in PAAL study

Exclusion criteria: :

 Inability to speak and understand English

 No access to a working phone or alternate phone for follow-up surveys

 Co-morbid respiratory condition including cystic fibrosis, chronic lung disease (BPD), lung cancer, tracheostomy that could interfere with the assessment of asthma-related outcome measures.

 Children residing in foster care or where consent cannot be obtained from a legal guardian.

['Pediatric Asthma Alert (PAAL)', 'Standard asthma education']

Pediatric Asthma Alert (PAAL)
Standard asthma education


RhEumatiC Heart diseAse Genetics

Summary: Rheumatic fever (RF) is an autoimmune disease that is mediated by the cellular and humoral immune response that follows an untreated pharyngeal Streptococcus pyogenes infection. The most serious complication is rheumatic heart disease (RHD), one of the most common problems facing children and young adults worldwide, which leads to chronic valvular lesions. It is estimated that 60% of all acute rheumatic fever cases will develop RHD.~The pathogenesis of RHD is complex with both environmental and genetic factors contributing to its etiology. The investigators know little about the genetic etiology, cellular events and modifiers of progression of RHD, and there exists a wide range of disease severity and progression to severe valve pathology.~Thus, the investigators will study the genetics of RHD in Rwanda, a country with a very high incidence of RHD, using a combination of next-generation targeted exome capture, transcriptomics, and expressed quantitative trait loci (eQTL) analysis.
Inclusion criteria: inclusion criteria:

 Clinical and echocardiographic signs of RHD using WHF criteria

Exclusion criteria: :

 Congenital heart disease


Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM Preserved)

Summary: A study to evaluate the effect of Atacand on patients with heart failure with preserved left ventricular function
Inclusion criteria: inclusion criteria:

 Male or female aged 18 or above

 Congestive Heart Failure with symptoms for more than 4 weeks before starting study

 Provision of informed consent

Exclusion criteria: :

 Current low blood pressure with symptoms

 Liver disease considered significant by the study doctor

 Pregnant or lactating females


Weekly Dosing of Malarone ® for Prevention of Malaria

Summary: The purpose of this study is to determine whether Malarone ®, which is a drug approved to prevent malaria when taken daily, will still effectively prevent malaria if taken weekly.
Inclusion criteria: inclusion criteria:

 A male or non-pregnant, non-lactating female 18 to 50 years of age (inclusive) at the time of screening

 Free of clinically significant health problems

 Baseline ECG before entering into the study

 Available to participate for duration of study (approximately 4 months, not including screening period)

 If the participant is female, not pregnant or lactating and willing to use contraception to prevent pregnancy

 BMI between 19 and 30

Exclusion criteria: :

 History of malaria or travel to a malarious country within the previous 12 months

 History of participation in a study in which potential exposure to malaria or vaccination against malaria occurred.

 Planned travel to malarious areas during the study period.

 History of malaria chemoprophylaxis within 60 days prior to time of study entry.

 Chronic use of antibiotics with anti-malarial effects

 Chronic use (defined as more than 14 days)of immunosuppressants or other immune-modifying drugs within six months of study entry.

 Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection

 Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination, ECG or laboratory screening tests

 Significant unexplained anemia

 History of sickle cell disease or sickle cell trait

 Seropositive for hepatitis B or hepatitis C

 History of splenectomy

 Pregnant or lactating female, or female who intends to become pregnant during the study

 Suspected or known current alcohol abuse as defined by the American Psychiatric Association in DSM IV

 History of a neuropsychiatric disorder (anxiety, depression, psychosis, schizophrenia)

 Chronic or active illicit and/or intravenous drug use

 History of allergy to atovaquone, proguanil or chloroquine

 History of psoriasis

 Concurrent participation in other research studies

['Atovaquone Proguanil', 'Procedure - malaria challenge']

Atovaquone Proguanil
Procedure - malaria challenge


Study With Migraid Device in Acute, Early Treatment of Migraine With Typical Aura

Summary: The purpose of the study was to assess the efficacy of Migraid in terms of preventing headaches in patients with migraine with typical aura. The secondary objectives were to assess whether Migraid is able to achieve pain relief and/or relief of migraine associated symptoms and to evaluate the safety and tolerability of the study treatment.
Inclusion criteria: inclusion criteria:

 Patients must have a current history of migraine with typical aura where the aura is usually followed by headache according to the International Headache Society (IHS) criteria.

 Patients are male or female. N.B. When female patients are treated for migraine attacks with triptans then the required precautions and safety measures should be taken in order to prevent pregnancy.

 Patients with an age between 18 and 65 years.

 Patients must have experienced 1-4 moderate (grade 2) or severe (grade 3) migraine attacks per month for at least two months prior to entry into the study.

 Patients must be willing to keep their prophylactic drug treatment for migraine unchanged.

 Patients must be able to distinguish migraine headaches from other headache types (e.g. tension-type headaches) at the onset of a migraine attack.

 Patients must be able to understand and complete the diary card

 Patients must be willing and able to give written informed consent prior to entry into the study.

 Patients must be willing and able to carry the Migraid and, if necessary, apply it in a public place.

Exclusion criteria: :

 Migraine patients with a typical aura but without any migraine headache thereafter.

 Patients with a history suggestive of ischaemic heart disease (IHD) or any present evidence of ischaemic heart disease (like angina pectoris, previous myocardial infarction, documented silent ischaemia, Prinzmetal's angina), or symptoms consistent with IHD.

 Patients suffering from coronary vasospasm or any atherosclerotic disease (cerebrovascular disease [CVD], peripheral vascular disease [PVD] or Raynaud's disease) which places them at increased risk of coronary ischaemia.

 Patients with a history of cerebrovascular accident (CVA) or transient ischaemic attacks (TIA).

 Patients with a supine diastolic blood pressure of > 95 mm Hg and/or systolic blood pressure > 160 mm Hg (treated or untreated) at Visit 1.

 Patients with a history of epilepsy or structural brain lesions which lower their convulsion threshold.

 Patients with tension-type headaches > 15 days/month in either of the two months prior to the study.

 Current abuse of opioid analgesics or other psychotropic drugs. History (within the past year) or current abuse of ergotamine (abuse as defined as > 10 mg/week). Current abuse of alcohol (according to local recommendations) or other drugs.

 Patients suffering from any severe concurrent medical condition which may affect the interpretation of efficacy and safety data or which otherwise contraindicates participation in a clinical study.

 Patients with a history of ophthalmoplegic, basilar or hemiplegic migraine.

 Patients with a history of impaired hepatic or renal function.

 Patients who have participated in a clinical trial within the previous 3 months or are planning to participate in another clinical research study at any time during this study.

 Patients with any concurrent medical or psychiatric condition that, in the investigator's opinion, may affect the interpretation of efficacy or safety data or which otherwise contraindicates participation in a clinical trial.

 Patients cannot be participating investigators, study co-ordinators, employees of investigators, or family members of any of the aforementioned.


The ACS Ethnicity Platelet Function Study

Summary: This study is being done to assess the effects of the CTP inhibitor on the function of your platelets (cells within your blood that are involved in the formation of blood clots) and to assess whether you have responded to the ticagrelor well enough to prevent the formation of blood clots within the stent or site in which angioplasty was performed.~Recent studies have looked at how racial differences can affect platelet reactivity, the way blood clots. But these studies have not looked at the way different racial backgrounds can affect the way the blood forms clots. Minorities, such as African-Americans are underrepresented. Therefore, we are conducting this platelet reactivity study to better understand if there are differences in how this drug affects African-Americans from how they affect Caucasian patients undergoing percutaneous coronary intervention and receiving ticagrelor. These data will be compared to a historical control of Caucasian patients who underwent similar platelet function testing.
Inclusion criteria: inclusion criteria:

 Female (post menopausal or surgically sterile) and/or male aged 18 years or older

 Presenting with ACS fulfilling the following:

 Symptoms or new ECG changes (ST segment elevation or depression of at least 1 mm in 2 or more contiguous leads on EKG)

 Elevation of biomarkers (CK-MB ≥2 ULN or troponin ≥ ULN)

 Self-identified as African-American

 Treatment with 75-100mg ASA daily

Exclusion criteria: :

 Any indication (atrial fibrillation, mitral stenosis or prosthetic heart valve, PE, DVT) for antithrombotic treatment during study period.

 Fibrinolytic therapy within 48 hours before randomization

 Concomitant therapy with a drug having possible interaction with ticagrelor. (concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer)

 Increased bleeding risk including: recent (<30 days) GI bleeding, any history of intracranial, intraocular, retroperitoneal, or spinal bleeding, recent (<30 days of dosing) major trauma, sustained uncontrolled hypertension (systolic blood pressure [SBP]>180mmHg or diastolic blood pressure [DBP]>100mmHg), history of hemorrhagic disorders that can increase the risk of bleeding, platelet count less than 100,000 mm3 or hemoglobin <10 g/dL.

 Any history of hemorrhagic stroke.

 Contraindication or other reason that ASA or ticagrelor should not be administered (e.g., hypersensitivity, active bleeding, major surgery within 30 days of dosing).

 Severe renal failure (creatinine clearance <30mL/min or patient requires dialysis)

 History of moderate or severe hepatic impairment with aspartate amino transferace, alanine amino transferase or total bilirubin > 1.5 x upper limit of the reference range.

 Pregnant or lactating women.

 Patients receiving any glycoprotein IIb/IIIa inhibitors <8 hours before platelet reactivity testing.


Plasma and Abscess Fluid Pharmacokinetics of Cefpirome and Moxifloxacin After Single and Multiple Dose Administration

Summary: Penetration of cefpirome and moxifloaxacin into abscess fluid of humans will be tested. Patients with an abscess scheduled for drainage will receive study drugs (single or multiple dose), pus samples and plasma samples will be collected and analyzed by High pressure liquid chromatography (HPLC). Pharmacokinetics of the study drugs in pus and plasma will be determined using a pharmacokinetic model.
Inclusion criteria: inclusion criteria:

 Female or male, aged between 18 and 90 years.

 Written informed consent.

 Abscess formation or abdominal cyst scheduled to drainage.

 Plasma creatinine <1.5 mg/dL

Exclusion criteria: :

 Pregnancy or lactation.

 Hemodialysis or hemofiltration

 Allergy or hypersensitivity against study drugs

 Massive edemata or hypernatremia

 Reduced liver function (Child-Pugh A, B, C)

 Relevant prolongation of QT-interval

 CNS-diseases which predispose for cramps

['cefpirome and moxifloxacin administration']


Safety and Effectiveness of Drug up Titration by Nurses Specialized in Heart Failure (HF) Patients

Summary: Introduction: Heart Failure (HF) generates multiple hospital admissions and mortality, which are reduced with the administration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) drugs (Level of Evidence A). The effect is dose-dependent. Nevertheless, dosages are suboptimal. European Guidelines 2012 recommend close monitoring and up-titration of drugs by HF nurses. Trials are needed to evaluate their effectiveness and safety. Objective: To compare doses achieved by patients of BB, ACEI, ARB II and MRA in 4 months ( % relative to target doses) in the intervention group (HF nurse) and in the control group ( cardiologist), adverse events, Left Ventricular Ejection Fraction (LVEF), New York Heart Association (NYHA), 6 min. walking test, quality of life, Nt-proBNP, readmissions and mortality. Hypothesis: Non-inferiority. Design: Multicenter randomized controlled trial. New (de novo) HF patients with LVEF ≤ 40%, NYHA II-III, without contraindications to BB of 17 Spanish hospitals will be included. Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration. In the control group doses are decided by the cardiologist clinical support and education being provided by nurses. Variables: age, sex, education, psycho-social level, Cardio Vascular Risk Factors (CVRF), NYHA, LVEF, ischemic cardiopathy., N-terminal pro B-type natriuretic peptide (Nt-proBNP), 6min. walking test, Creatinine/Glomerular Filtration Rate (GFR), Potassium (K), haemoglobin, Blood Pressure (BP), Heart Rate (HR), mg./drug, European Heart Failure Self-Care Behaviour Scale (EHFScBS), Minnesota Living with Heart Failure questionnaire (MLHFQ), European Quality of life Scale (EQ-5D). Expected Results: If our hypothesis were confirmed, evidence would be provided on the effectiveness of this healthcare management, that could be economically evaluated in future studies. A qualitative study also will be undertaken to explore barriers and facilitators to implementation
Inclusion criteria: inclusion criteria:

 Patient with de novo heart Failure and LVEF <= 40% admitted in hospital, without contraindications for BB prescription with cardiologist up-titration prescription and without having achieved BB target dose previous discharge and signing informed consent.

Exclusion criteria: :

 Contraindications for BB.

 Living in a nursing home.

 Life expectancy < 6 months.

 Unable to self-care or mental disease without caregiver.

 Unable to weight

 Without phone

 Unable to go to clinic visit.

['Heart Failure (HF) nurse up-titration', 'Heart Failure (HF) cardiologist up-titration']


Open-label Vitamin D Trial for Patients With Cystic Fibrosis and Allergic Bronchopulmonary Aspergillosis

Summary: The purpose of this study is to see if giving people with CF and ABPA enough vitamin D to make their blood levels of the vitamin higher, will reduce the allergic response in their body and make the symptoms caused by ABPA better.
Inclusion criteria: inclusion criteria:

 Male or female ≥ 12 years of age at enrollment

 Confirmed diagnosis of CF based on the following criteria:

 One or more clinical features consistent with the CF phenotype AND (b or c)

 Positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis)

 two identifiable mutations consistent with CF

 Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

 Clinically stable at enrollment as assessed by the site investigator

 Past or present respiratory culture positive for Aspergillus fumigatus

 IgE ≥ 250 and/or presence of class II or higher aspergillus specific IgE on enrollment

 Ability to comply with medication use, study visits and study procedures as judged by the site investigator -

Exclusion criteria: :

 1. Systemic corticosteroids (1 mg/kg if < 20 kg or > 20 mg of prednisone per day),.

 2. Investigational drug use within 30 days of screening 3. Laboratory abnormalities at screening

 a. Serum Calcium > 11 mg/dl b. 25(OH) D > 50 ng/ml at screening. c. Creatinine ≥ 1.5, or estimated GFR <60 by Cockcroft-Gault or MDRD equation. d. LFT≥ 3xULN

 4. History of transplantation or currently on lung transplant list 5. Positive serum pregnancy test at screening (to be performed on all post-menarche females) 6. Pregnant, breastfeeding, or if post-menarche female, unwilling to practice birth control during participation in the study 7. Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data 8. Diagnosis of HIV and a CD4+ T cell count below 500 cells/ml or active hepatitis B or C infection.

 9. Undergoing therapy for non-tuberculous mycobacterial infection

['Cystic Fibrosis', 'Allergic Bronchopulmonary Aspergillosis']

Cystic Fibrosis
Allergic Bronchopulmonary Aspergillosis


Difference Between Central and Peripheral Arterial Blood Oxygen Saturation With Different CPB Strategy

Summary: Femoro-femoral cardiopulmonary bypass with retrograde perfusion is needed for totally thoracoscopic cardiac surgery. one of the major complication of retrograde perfusion is organ hypoperfusion.~Arterial blood gas analysis can help to detect hypoperfusion or hypoxia during retrograde perfusion. However,whether the arterial oxygenation status from different parts of the body are the same in the condition of retrograde perfusion have not been studied.~The present study is aimed to determine if there is difference in the arterial oxygenation between peripheral arterial and aortic root during the period of retrograde perfusion.In addition, the impact of artificial ventilation on the difference of arterial oxygenation will also be investigated.
Inclusion criteria: inclusion criteria:

 age > 18 years old

 undergoing totally thoracoscopic cardiac surgery with cardiopulmonary bypass

Exclusion criteria: :

 without informed consent

 pregnancy

['Bypass Complications', 'Disorder of Blood Gas']

Bypass Complications
Disorder of Blood Gas

:

 without informed consent

 pregnancy


Evaluation of a Novel Electronic Urine Output Monitor (eUOM)

Summary: Urine output and urine drain line pressure were monitored while urine was drained into either:~Accuryn Urine Output Monitor (Potrero Medical) OR~Criticore Monitor (Bard Medical)
Inclusion criteria: inclusion criteria:

 Patient must ≥ 18 years of age

 Patient has a Foley catheter and urine collection system is in place per standard clinical decision

 Estimated length of placement of the Foley is 48 hours minimum

 Burn injury ≥ 20% and ≤ 80% total body surface area (TBSA)

 Subject or subject's legally authorized representative is able to give informed consent before entering the study

Exclusion criteria: :

 Currently pregnant or breastfeeding

 Clinical signs or symptoms of a urinary tract infection (UTI)

 Clinical signs or symptoms of a vaginal infection

 Currently has bladder or urethral trauma

 Use of investigational drug/device therapy within the past 4 weeks


Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation

Summary: The purpose of this study is to determine whether a body weight adjusted dose of thyroxin is superior to treatment guided by laboratory results of thyroxin hormones in patients with central hypothyroidism. Moreover beneficial effects of triiodthyronine supplementation are investigated.
Inclusion criteria: inclusion criteria:

 hypopituitarism of at least 3 axes (TSH plus gonadotropin, somatotropin, corticotropin or ADH deficiency)

 termination of surgical or radiation treatment of pituitary tumors at least six month before study entry

 BMI of 20 - 39.9 kg/m2

 non-smoking status.

Exclusion criteria: :

 history of cardiovascular or pulmonary diseases

 current thyroxin dosage > 1.6 µg/kg bw

 pregnancy

 epilepsy

 cerebrovascular diseases

 nodular goiter

['Secondary Hypothyroidism', 'Hypopituitarism', 'Hyperlipidemias']

Secondary Hypothyroidism
Hypopituitarism
Hyperlipidemias


Subcuticular Suture Versus Staples for Closure of the Skin After Caesarean Section.

Summary: The Purpose of this study is to compare two methods for closure of the skin after caesarean section on the same patient; staples and subcuticular sutures. The study is performed on two separate groups of patients: 1. Woman having cesarean section for the first time and have not previously had abdominal surgery through a lower abdominal transverse incision. 2. Woman, who have previously had a caesarean section done. The following parameters are registered:~An objective evaluation of the two ends of the scar 6 months postoperatively.~A patient evaluation of the two ends of the scar 6 months postoperatively.~The difference in pain in the two ends of the scar 1 day postoperatively (blinded).~The difference in pain in the two ends of the scar 7 days, 3 and 6 months postoperatively.~The rate of infection.
Inclusion criteria: inclusion criteria:

 Woman having elective or level III caesarean section. Level III caesarean section is defined as being ordered more than 30 minutes before surgery is started.

 Woman who speak and understand Danish

 Woman who can give informed consent.

Exclusion criteria: :

 Level I or II caesarean section (ordered less than 30 min. before surgery is started).

 Diabetics (this does not include gestational diabetes).

 Infection

 Regular treatment with immunosuppressives

 Alcohol or drug abuse

 Age under 18

 Chronic pain disease eg fibromyalgia, rheumatoid arthritis

 BMI over 35

 Previous abdominal surgery through lower transverse abdominal incision (only applicable to woman having caesarean section for the first time).

['Staples left, subcuticular suture right', 'Subcuticular suture left side and staples right']


Experimental Human Malaria Infection After Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis

Summary: Malaria is one of the major infectious diseases in the world with a tremendous impact on the quality of life significantly contributing to the ongoing poverty in endemic countries. It causes almost one million deaths per year, the majority of which are children under the age of five. The malaria parasite enters the human body through the skin, by the bite of an infected mosquito. Subsequently, it invades the liver and develops and multiplies inside the hepatocytes. After a week, the hepatocytes burst open and the parasites are released in the blood stream, causing the clinical phase of the disease.~As a unique opportunity to study malaria immunology and efficacy of immunisation strategies, a protocol has been developed in the past to conduct experimental human malaria infections (EHMIs). EHMIs generally involve small groups of malaria-naïve volunteers infected via the bites of P. falciparum infected laboratory-reared Anopheline mosquitoes. Although potentially serious or even lethal, Plasmodium falciparum (P.falciparum) malaria can be radically cured at the earliest stages of blood infection where risks of complications are virtually absent.~The investigators have shown previously, that healthy human volunteers can be protected from a malaria mosquito challenge by immunization with mosquito-bites under chloroquine prophylaxis (CPS immunization). However, it is unknown whether this protection is based on immunity directed towards the liver- or the blood stage of the disease. For future development of vaccines and understanding of protective immunity to malaria, it is important to investigate at which level protective immunity is generated by CPS immunization. Therefore, we aim to investigate whether CPS immunization confers protection to a blood-stage challenge.
Inclusion criteria: inclusion criteria:

 Age > 18 and < 35 years healthy volunteers (males or females)

 Good health based on history and clinical examination

 Negative pregnancy test

 Use of adequate contraception for females

 All volunteers must sign the informed consent form demonstrating their understanding of the meaning and procedures of the study

 Volunteer agrees to inform the general practitioner and agrees to sign a request to release medical information concerning contra-indications for participation in the study

 Willingness to undergo a Pf mosquito or blood stage challenge

 For volunteers not living in Nijmegen: agreement to stay in a hotel room close to the trial center during a part of the study (for groups 1 and 3 from challenge day till 3 days after treatment, for groups 2 and 4 from 5 days after challenge till 3 days after treatment)

 Reachable (24/7) by mobile phone during the whole study period

 Living with a third party that could contact the clinicians in case of alteration of consciousness or agreement to stay in a hotel room close to the trial center during a part of the study (for groups 1 and 3 from challenge day till 3 days after treatment, for groups 2 and 4 from 5 days after challenge till 3 days after treatment)

 Available to attend all study visits

 Agreement to refrain from blood donation to Sanquin or for other purposes, during the study period until 393

 Willingness to undergo HIV, hepatitis B and hepatitis C tests

 Negative urine toxicology screening test at screening visit and day before challenge

 Willingness to take a prophylactic regime of chloroquine and curative regimen of Malarone®

Exclusion criteria: :

 History of malaria

 Plans to travel to malaria endemic areas during the study period

 Plans to travel outside of the Netherlands during the challenge period

 Previous participation in any malaria vaccine study and/or positive serology for Pf

 Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers

 History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)

 History of arrhythmias or prolonged QT-interval

 Positive family history in 1st and 2nd degree relatives for cardiac disease < 50 years old

 An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system

 Clinically significant abnormalities in electrocardiogram (ECG) at screening

 Body Mass Index (BMI) below 18 or above 30 kg/m2

 Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis

 Positive HIV, HBV or HCV tests

 Participation in any other clinical study within 30 days prior to the onset of the study

 Enrollment in any other clinical study during the study period

 Pregnant or lactating women

 Volunteers unable to give written informed consent

 Volunteers unable to be closely followed for social, geographic or psychological reasons

 Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study

 A history of psychiatric disease

 Known hypersensitivity to anti-malaria drugs

 The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period

 Contra-indications to Malarone® or chloroquine including treatment taken by the volunteer that interferes with Malarone® or chloroquine

 Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia

 Co-workers of the departments of Medical Microbiology or Internal Medicine of the RUNMC

 A history of sickle cell anemia, sickle cell trait, thalassemia, thalassemia trait or G6PD deficiency

['Chloroquine prophylaxis', 'Immunization', 'Plasmodium falciparum Bloodstage challenge', 'Plasmodium falciparum mosquito challenge', 'Malarone treatment']


Nurse-Led Heart Failure Care Transition Intervention for African Americans: The Navigator Program

Summary: Heart failure (HF) affects over 5 million Americans with HF morbidity reaching epidemic proportions. Annual rates of new and recurrent HF events including hospitalization and mortality are higher among African Americans. In this study, the investigators are testing an interdisciplinary model for heart failure care, with focus on enhancing self management and use of telehealth, which has significant potential to improve self management and outcomes.~The main purpose of this study is to learn how to help African Americans with heart failure care for themselves at home. We hope to find out if a team including a nurse and community health navigator using a computer telehealth device can help people with heart failure stay healthier. The team will help people with heart failure to manage their medication, monitor their symptoms and weigh themselves every day after they leave the hospital. The team will also help people with heart failure learn to solve problems that may keep them from following their treatment plan.
Inclusion criteria: inclusion criteria:

 hospitalized with admitting diagnosis of heart failure in prior 8 weeks

 self-identified as African American

 community-dwelling (i.e., not in a long-term care facility)

 residence within a predefined radius in Baltimore City

 working telephone in their home

 provide signed informed consent

Exclusion criteria: :

 cannot speak or understand English

 severe renal insufficiency requiring dialysis

 acute myocardial infarction within preceding 30 days

 receiving home care services for HF post discharge

 legally blind or have major hearing loss

 screen positive for cognitive impairment on the Mini-cog at baseline

 unable to stand independently on a weight scale (limited ability to participate in HAT system)

 weigh more than 325 pounds (exceed scale capacity)

 serious or terminal condition such as psychosis or cancer (actively receiving chemo or radiation)

 pregnant

['Heart Failure Self Care Support', 'Usual heart failure care']

Heart Failure Self Care Support
Usual heart failure care


TACTICS (Targeting Adherence to Cholesterol-lowering Therapy to Improve Control Study)

Summary: Background:~This is a randomized controlled trial (RCT) of two novel behavioral interventions to enhance treatment adherence and improve low-density lipoprotein cholesterol (LDL) in diabetes. Among adults with diabetes, high LDL greatly increases their risk for cardiovascular disease (CVD). Despite the proven efficacy of LDL control(<100 mg/dL) in preventing CVD, the control rate is low. Poor adherence to treatment(diet, exercise and medication) is the main reason for this poor control.~Aims: This study will test two telephone-delivered interventions, a Transtheoretical stage-matched intervention (SMI) and a Prospect theory-based framing effects intervention (FEI). The investigators hypothesize that both SMI and FEI will be more effective in improving LDL control than an attention placebo intervention (API) at 6 months. SMI and FEI will also be more effective in increasing adherence to medications, diet and exercise than API at 6 months.~Methods:~The investigators will recruit 246 adults with diabetes and high LDL despite being on medications. Key outcomes are adherence to diet, exercise and medication, and LDL control. The interventions will be standardized and fidelity of intervention maintained. Using a blinded RCT the investigators will test the effect of SMI and FEI compared to API on LDL control and adherence. All analyses will be intent to treat.~Significance:~This project will provide important information to improve diabetes-related behavior and lead to the implementation of novel interventions for lowering LDL in primary care settings among adults with diabetes. It may also provide the scientific rationale to use such approaches to control other risk factors in diabetes.
Inclusion criteria: inclusion criteria:

 Adults with diabetes

 LDL greater than or equal to 100

 Cholesterol-lowering drug therapy for > 6 months

 A working telephone

 At least 2 primary care visits in the past 1.5 years

Exclusion criteria: :

 Poor short-term survival (< 1 year)

 Inability to understand English

 Recent major surgery (< 3 months)

 Patients temporarily in the area

 Inability to provide consent

['stage-matched intervention', 'framing effects intervention', 'attention placebo intervention']

stage-matched intervention
framing effects intervention
attention placebo intervention


Safety & Immunogenicity of 13vPnC in HIV-Infected Subjects Aged 18 or Older Who Were Previously Immunized With 23vPS

Summary: The study will evaluate the safety, tolerability and immunogenicity of a 13-valent pneumococcal conjugate vaccine (13vPnC) in HIV-infected subjects 18 years of age or older who have been previously immunized with at least one dose of 23-valent pneumococcal polysaccharide vaccine (23vPS). All subjects will receive 3 doses of 13vPnC, with each study vaccine dose given approximately 6 months apart.
Inclusion criteria: inclusion criteria:

 Male or female subjects aged 18 years or older at the time of enrollment.

 All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control from the signing of the informed consent form (ICF) until 3 months after the last dose of investigational product.

 Documented vaccination with 1 or more doses of 23vPS at least 6 months before study enrollment.

 CD4+ T-cell count >= 200 cells/µ, obtained on the most recent 2 occasions within 6 months before the first investigational product vaccination.

 HIV-infected subjects with viral load <50,000 copies/mL, obtained on the most recent 2 occasions within 6 months before the first investigational product vaccination.

 Subject is receiving a stable dose of HAART for at least 6 weeks prior to the first investigational product vaccination, or not currently receiving antiretroviral therapy.

 Subject is expected to be available for the entire study period (approximately 18 months) and can be contacted by telephone.

 Subject must be able to complete an electronic diary (e-diary) and complete all relevant study procedures during study participation.

 Subject is deemed to be eligible for the study on the basis of medical history, physical examination, and clinical judgment. (Note: Subjects with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease 6 weeks before investigational product vaccination, are eligible.)

Exclusion criteria: :

 Subjects with active AIDS related illness, including opportunistic infections or malignancy.

 Evidence of current illicit substance and/or alcohol abuse, that in the investigator's opinion, precludes the subject from participating in the study or interferes with the evaluation of the study objectives..

 Receipt of any licensed or experimental pneumococcal conjugate vaccine prior to enrollment.

 Contraindication to vaccination with pneumococcal conjugate vaccine.

 Previous anaphylactic reaction to any vaccine or vaccine-related component.

 History of culture-proven invasive disease caused by Streptococcus pneumoniae within the last year.

 Current anticoagulant therapy or a history of bleeding diathesis or any condition associated with prolonged bleeding time that would contraindicate intramuscular injection. (Note: Use of antiplatelet drugs, such as aspirin and clopidogrel, is permitted.)

 Pregnant or breastfeeding women, as defined by history or positive human chorionic gonadotropin (hCG) urine test. All women of childbearing potential must have a urine pregnancy test.

 History of active hepatitis with elevation in pretreatment aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >5 times the upper limit of normal within the last 6 months.

 Serious chronic disorder or any other disorder that, in the investigator's opinion, precludes the subject from participating in the study or interferes with the evaluation of the study objectives. (Note: Serious chronic disorders include metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, and clinically unstable cardiac disease).

 Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of, the study, or could preclude the evaluation of the subject's response.

 History of splenectomy.

 Receipt of any blood products, including immunoglobulin, within 42 days before investigational product vaccination until the last blood draw for the study (approximately 13 months after the first investigational product vaccination).

 Evidence of dementia or other severe cognitive impairment.

 Subject who is, in the opinion of the investigator, unable to receive a vaccination in the deltoid muscle of either arm because of insufficient muscle mass.

 Participation in another study using investigational product from 28 days before study enrollment until the blood draw at visit 6. Between the blood draw at visit 6 and the 6 month follow-up telephone call (visit 7), use of investigational product must be discussed with the Medical Monitor. (Note: Participation in purely observational studies is acceptable.)

 Residence in a nursing home, long-term care facility, or other institution or requirement of semi-skilled nursing care. An ambulatory resident of a retirement home or village is eligible for the trial.

 Subject who is a direct relative (child, grandchild, parent, or grandparent) of study personnel, or who is study personnel.

 Temporary Delay Criteria:

 Current febrile illness (oral temperature of =38.0°C [100.4°F]) or other acute illness within 48 hours before study vaccine administration.

 Currently receiving antibiotic therapy, or has completed a course of antibiotic therapy within 10 days before study vaccine administration.

 Receipt of novel influenza A (H1N1) vaccine within 14 days before investigational product vaccination (seasonal influenza vaccine can be given at any time at the discretion of the investigator).

['13-valent pneumococcal conjugate vaccine', 'Blood draw']

['HIV Infections', 'Pneumococcal Infections']


Controlled Trial of ABELADRUG200 in Closed, Severe Head Injury

Summary: This is a randomized, controlled clinical trial at three sites to determine the safety and preliminary efficacy of the study drug to treat severe head trauma (GCS 4-8). It is hypothesized that the drug may lower pressure in the brain, reduce mortality and the patient may have improved neurological function following treatment.
Inclusion criteria: inclusion criteria:

 Diagnosis TBI

 GCS 4-8

 Age 16-70

Exclusion criteria: :

 Multiple trauma resulting in shock

 Bilateral absent pupil response

 Time from injury > 6 hours

 Brain tumor or mass effect secondary to hemorrhage or brain surgery

 Pregnancy

 Confounding condition or injury

 Spinal cord injury

 Sustained high blood pressure or arterial oxygen saturation


Minoxidil 1% for Eyebrow Enhancement

Summary: The purpose of the study is to compare efficacy and safety of minoxidil 1% versus placebo in enhancement of eyebrows.
Inclusion criteria: inclusion criteria:

 male or female aged 18-60 years

 hypotrichosis of eyebrows

 healthy

 informed consent obtained

Exclusion criteria: :

 underlying diseases

 alopecia areata or trichotillomania

 thyroid diseases

 pregnancy or breast feeding

 previous eyebrow tattoo, trauma or accident.

 history of eyebrow or hair medications in 6 months

 history of minoxidil or its ingredient allergy

 history of eyebrow surgery.

['Eyebrow Hypotrichosis', 'Thin Eyebrow']


Safety and Immunogenicity of Formulations of Dengue Vaccines in Healthy Flavivirus-Naïve Adults

Summary: This is part of an ongoing effort to develop a satisfactory dengue vaccine:~Primary objective:~To describe the safety after each vaccination with bivalent and tetravalent formulations of dengue vaccine candidates.~To describe the immune response after each vaccination of dengue vaccine.
Inclusion criteria: inclusion criteria :

 Healthy as determined by medical history, clinical examination, and biological safety parameters

 Aged 18 to 45 years on the day of inclusion.

 Informed consent form signed.

 Able to attend all scheduled visits and to comply with all trial procedures

 For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination and at least 4 weeks after the last vaccination.

Exclusion criteria:  :

 History of thymic diseases or thymectomy.

 For a woman of child-bearing potential, known or suspected pregnancy or positive pregnancy test

 Breast-feeding

 Current abuse of alcohol or drug addiction that may interfere with the subject's ability to comply with trial procedures.

 Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.

 Human Immunodeficiency Virus (HIV), Hepatitis B (HBs Ag) or Hepatitis C (HC) seropositivity in blood sample taken at screening.

 Laboratory abnormalities considered clinically significant upon the Investigator's judgment or above the intensity thresholds (defined in the protocol) in blood sample taken at screening.

 Participation in another clinical trial in the 4 weeks preceding the first trial vaccination.

 Planned participation in another clinical trial during the present trial period.

 Previous residence in or travel of more than 2 weeks to areas with high dengue infection endemicity.

 Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or a vaccine containing the same substances (i.e. egg, egg products, proteins of rodent or neural origin, gelatin, and thimerosal.

 History of urticaria after hymenoptera envenomation.

 History of flavivirus infection as reported by the subject.

 Previous vaccination against flavivirus diseases (including Japanese encephalitis, tick-borne encephalitis, and yellow fever).

 Planned travel during the present trial period to areas with high dengue infection endemicity.

 Congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroid therapy (at a dose of a t least 10 mg).

 Chronic illness at a stage that could interfere with trial conduct or completion.

 Blood or blood-derived products received in the past 3 months.

 Any vaccination in the 4 weeks preceding the first trial vaccination.

 Vaccination planned in the 4 weeks following any trial vaccination.

 Flavivirus vaccination planned during the present trial period.

['Bivalent CYD-1,3 Dengue (Vero) + Bivalent CYD-2,4 Dengue (Vero)', 'Bivalent CYD-1,3 Dengue (Vero) + Bivalent CYD-2,4 Dengue (Vero)', 'Tetravalent blending VDV-2/CYD-1,3,4 Dengue (Vero)', 'Tetravalent CYD-1,2,3,4 Dengue (Vero)', 'JE-VAX®: Japanese encephalitis virus vaccine inactivated + Tetravalent CYD-1,2,3,4 Dengue (Vero)']

['Dengue Virus', 'Dengue Fever', 'Dengue Hemorrhagic Fever', 'Dengue Diseases']

Dengue Virus
Dengue Fever
Dengue Hemorrhagic Fever
Dengue Diseases


e-CHAMP: Enhancing Care for Hospitalized Older Adults With Memory Problems

Summary: The purpose of this study is to evaluate the effectiveness of a cognitive screening program coupled with a computerized decision support system in improving the quality of care for hospitalized older adults with cognitive impairment.
Inclusion criteria: inclusion criteria:

 65 years of age or older

 Hospitalized in a medical ward

 Able to speak English

 Cognitive impairment based on screening at time of hospital admission

Exclusion criteria: :

 Previously enrolled in the study during prior hospitalization (for multiple admissions; only data from the first admission will be used)

 Enrolled in another clinical trial

 Does not have cognitive impairment based on screening at time of hospital admission

['e-CHAMP (Enhancing Care for Hospitalized Older Adults with Cognitive Impairment)', 'Standard Care']


Cerebral Palsy Hip Health Related Quality of Life

Summary: Children with cerebral palsy are at an increased risk of having their hips move partially or completely out of joint. This can cause pain and restrict movement at the hip, making sitting in a wheelchair uncomfortable and make personal care difficult. This condition may be treated with surgery. Surgeons use x-rays taken before and after the surgery to determine whether or not the surgery has been successful. However, it is also important to know whether the surgery has improved life from the child or the caregiver's point of view. The investigators will also evaluate if waiting for surgery affects the child. This information will be added to results from a physical exam and an evaluation of the child's x-rays for a more complete picture of how this surgery impacts the lives of our patients. It is predicted that that the health-related quality of life of children with cerebral palsy will improve following surgery.
Inclusion criteria: inclusion criteria:

 Ages 4-18

 Undergoing surgical treatment for hip subluxation or dislocation

 Diagnosis of cerebral palsy or similar condition causing motor impairment

 Consent to participate

Exclusion criteria: :

 Diagnosis of neuromuscular disorders other than cerebral palsy

 younger than 4, older than 18

 Reimer's migration percentage <40%

['Cerebral Palsy', 'Patient Undergoing Hip Surgery', 'Quality of Life']

Cerebral Palsy
Patient Undergoing Hip Surgery
Quality of Life