Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy

Summary: Dilated cardiomyopathy (DCM) is a poorly understood cause of systolic heart failure and is the most common indication for heart transplantation worldwide. Despite advances in medical and device therapy, the 5-year mortality of patients with DCM remains high.~Patients diagnosed of dilated cardiomyopathy with a NYHA functional class of II to IV and left ventricular ejection fraction(LVEF) <35% were selected for randomized controlled study of the efficacy and safety of high dose Renin-angiotensin system (RAS) inhibitor (benazepril or valsartan), in comparison with low dose RAS inhibitor(benazepril or valsartan) and standard beta-adrenergic blocker therapy (metoprolol). The primary endpoint was all cause death or admission for heart failure. Additional prespecified outcomes included all-cause death, cardiovascular death, all-cause admission, heart failure admission. Secondary cardiovascular outcomes included the changes from baseline to the last available observation after treatment in NYHA functional class, quality-of-life scores, LVEF, LVEDD, mitral regurgitation and wall-motion score index assessed by ECG. Adverse events were reported during in-hospital observation and follow-ups.
Inclusion criteria: inclusion criteria:

 Diagnosis of dilated cardiomyopathy

 Left ventricular ejection fraction < 35%

 NYHA Functional classes of II-IV

 Symptomatic but not rapidly deteriorating 1 month before enrollment

 Signed informed consent

Exclusion criteria: :

 Contradictions and intolerance of the studied drugs:

 supine systolic arterial blood pressure < 90 mmHg,

 renal artery stenosis >50%,

 pregnancy or lactation,

 impaired renal function (estimated glomerular filtration rate < 60 ml/min/1.73m2,

 impaired liver function (total bilirubin >2 times upper limit of normal,

 serum aspartate AST or alanine ALT >3 times the upper limit of normal),

 hemoglobin less than 8 mg/dl, hyperkalaemia (serum potassium >5.5mmol/l),

 obstructive lung disease,

 advanced atrioventricular block,

 any co-morbidity with impact on survival, and

 known intolerance to benazepril, valsartan and metoprolol succinate;

 HF secondary to a known cause:

 coronary artery disease based on coronary angiography (≥50% stenosis in ≥1 of the major coronary arteries) and/or a history of myocardial infarction or angina pectoris,

 acute or subacute stage of myocarditis,

 primary valve disease,

 diabetes mellitus,

 excessive use of alcohol or illicit drugs;

 Expected or performed cardiac resynchronization therapy and heart transplantation.


Amlodipine/Atorvastatin (Caduet®) Drug Use Investigation (Regulatory Post Marketing Commitment Plan)

Summary: In this survey, to collect the safety and efficacy information of Amlodipine /Atorvastatin (Caduet® Combination Tablets) in daily medical practice will be examined. In addition, the necessity of special Investigation and post-marketing clinical studies will be examined, while investigating unexpected adverse drug reactions during the survey period and understanding of the status of frequency of adverse drug reactions in daily medical practice.
Inclusion criteria: inclusion criteria:

 Male or Female subjects intend to treat their cardiovascular disease who are prescribed Amlodipine /Atorvastatin (Caduet®) Combination Tablets by their Physicians

Exclusion criteria: :

 Subjects who have been prescribed Amlodipine /Atorvastatin (Caduet®) Combination Tablets before.

['Hypertension', 'Angina Pectoris', 'Hypercholesterolemia', 'Familial Hypercholesterolemia']

Hypertension
Angina Pectoris
Hypercholesterolemia
Familial Hypercholesterolemia


Transanal Endoscopic Microsurgery Versus Endoscopic Submucosal Dissection For Large Rectal Adenomas

Summary: Objective: Recent non-randomized studies suggest that extended endoscopic submucosal dissection (ESD) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, ESD might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, ESD appears to be associated with fewer complications. In a randomized trial we will compare the cost-effectiveness and cost-utility of TEM and ESD for the resection of large rectal adenomas.~Study design: 15 centers will participate in this multicenter randomized trial comparing TEM versus ESD.~Study population: Patients with a large rectal adenoma (≥2cm), located between 2 and 15 cm from the anal verge. Invasive cancer is excluded by histopathology and endoscopic ultrasonography. Patients must be in a health condition that permits general anesthesia.~Interventions: Patients will be randomized between~a. TEM: under general anesthesia b. ESD under sedation~a TEM tube will be inserted in the rectum. With specialized instruments the adenoma will be dissected en bloc by a full thickness excision, after which the patient will be admitted to the hospital.~an endoscope will be inserted into the rectum and the submucosa underneath the lesion will be injected with saline to lift the adenoma. With an endoscopic knife (Insulated Tip Knife, Olympus or Water Jet, Erbe) the lesion will be resected through the submucosal plane in an eb-bloc fashion, after which the patient will be observed for at least 24h in-hospital.~Primary Endpoint: incidence of recurrence at 12 months~Secondary Endpoints:~morbidity, subdivided into major (requiring surgery) and minor (requiring endoscopic or medical intervention) anorectal function. disease specific and general quality of life; number of days not spent in hospital from initial treatment until 2 years afterwards; adenoma~Sample size: Assuming a comparable baseline recurrence rate for TEM and ESD of 6% and considering an upper limit of 10% for ESD to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 60 patients are needed per group. These numbers provide sufficient power to reveal relevant differences in expected morbidity and in number of days not spent in hospital.~Economic evaluation: A cost-effectiveness and cost-utility analysis of ESD against TEM for large rectal adenomas from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as primary outcome measures.
Inclusion criteria: inclusion criteria:

 Diagnosed with a large non-pedunculated rectal adenoma (sessile or flat) with a largest diameter of ≥2 cm (estimated by an opened resection snare of 20 or 30 mm).

 The lower and upper borders of the adenoma are located at ≥2 cm and ≤15 cm from the anal verge, respectively.

 Biopsies of the lesion did not show malignant neoplastic tissue on histopathological evaluation; only lesions with low or high grade dysplasia are suitable for inclusion.

 During flexible video endoscopy there are no signs of endoscopic suspicion for submucosal invasive cancer (Kudo pit pattern type V; excavated/depressed type morphology; fold convergence; or large smooth nodule >1 cm in a flat lesion) (33). In case of doubt, patients will undergo EUS as described at (2).

 In case doubt remains after flexible video endoscopy, endoscopic ultrasonography (EUS) of the rectal adenoma should exclude invasion into the submucosal layer and exclude pathological lymphadenopathy (lymph nodes >1 cm). When pathological lymph nodes are present, fine needle aspiration will be performed to exclude lymph node metastasis (N+ disease).

 If not performed already, total colonoscopy will be done to detect and remove all synchronous colonic adenomas or cancers first. Cecal intubation must be confirmed by identification of the appendiceal orifice and ileocecal valve.

 The general health condition of the patient permits general anesthesia (ASA- classification I-III).

 Absence of non-correctable coagulopathy (international normalized ratio >1,5, or platelet count <90 × 109/l).

 Patient age of 18 years or older.

Exclusion criteria: :

 Preoperative histologically detected malignancy

 Previous anorectal surgery

 Contraindications to general anaesthesia

['TEM - Transanal Endoscopic Microsurgery', 'ESD - Endoscopic Submucosal Dissection']

TEM - Transanal Endoscopic Microsurgery
ESD - Endoscopic Submucosal Dissection


Impact of Antibiotic Treatment of Group A Streptococcal Blistering Distal Dactylitis in Children

Summary: Single-center prospective study to assess the clinical course of group A streptococcal blistering distal dactylitis in children after antibiotic treatment.
Inclusion criteria: inclusion criteria:

 Children 0-18 years

 Distal blistering dactylitis collected or not collected

 Positive rapid Group A Streptococcus test

 Informed consent signed by the parents

Exclusion criteria: :

 Subungual or pulp Whitlow

 Children not affiliated to the social security scheme

 Refusal by the parents to participate in the study

['Positive rapid GAS test', 'Negative rapid GAS test']

Positive rapid GAS test
Negative rapid GAS test


Diet and Prevention of Ischemic Heart Disease: a Translational Approach

Summary: The objective of this study is to test the effect of substitution dietary guidelines that are specifically aimed at the prevention of ischemic heart disease (IHD) on the dietary intake in the general Danish population.
Inclusion criteria: inclusion criteria:

 healthy men and women aged 30 to 65 years who has one or more self-assessed ischemic heart disease risk factors at screening: physical inactivity, overweight or obese (BMI ≥ 25/m2 ), waist circumference (≥ 80 cm for women, ≥ 94 cm for men). In addition, the participants should have the motivation and willingness to be randomized to any of the three groups, and to do their best to follow the given protocol .

Exclusion criteria: :

 no internet access or no access to a computer, smoking, pregnancy, or breast-feeding or planning to become pregnant within the next 12 months, a history of cardiovascular disease, type 2 diabetes, chronic disease / disorders that may affect the results of the study, substance abuse within the past 12 months, regular alcohol consumption > 21 units / week for men or > 14 units/ week for women, allergy or intolerance to food groups in the dietary guidelines, supplements with mega doses of nutrients that can have potential impact on ischemic heart disease risk markers (eg . fish oils).


Secondary Lactose Intolerance Due to Chronic Norovirus Infection

Summary: The objective of this study is to determine the prevalence of secondary lactose intolerance in renal transplant recipients (RTR) with chronic norovirus infection.~In the investigators cohort of 1000 renal transplant recipients (RTRs) in the University Hospital of Zurich, the investigators are currently aware of 10 patients with chronic norovirus infection, which was proven by positive polymerase chain reaction (PCR) analysis of recent stool samples, whereas chronic virus shedding is defined as more than two PCR positive samples in an interval of at least one month. Concomitant viral (other than norovirus), bacterial or parasitic (particularly Gardia lamblia) intestinal infections are excluded by negative stool cultures and PCR analyses, respectively. Main exclusion criterion for the present case series is a concomitant intestinal infection (other than norovirus) and primary lactose intolerance, which is previously excluded by absence of the CC genotype of the DNA variant -13910 T/C upstream in the LCT gene. After obtaining written and oral informed consent, the investigators perform a lactose hydrogen breath (LH2BT) test and a lactose tolerance test (LTT) in all eligible RTRs with proven chronic norovirus infection irrespective of current abdominal symptoms.~The study population (N=10) is divided into two groups according to the gastrointestinal symptoms (asymptomatic versus symptomatic, such as chronic diarrhoea or diffuse abdominal discomfort). The investigators chose the cut-off three or more stools per day as indicative of diarrhoea for the purpose of this study. RTRs with otherwise unexplainable chronic diarrhoea but absent norovirus infection serve as control group (N=10).
Inclusion criteria: inclusion criteria:

 - Renal transplant recipient (RTR) with proven diagnosis of chronic norovirus infection, whereas chronic virus shedding is defined as more than two polymerase chain reaction (PCR) positive samples in an interval of at least one month (case group) or chronic diarrhoea defined as more than three bowel movements per day since more than four weeks (control group).

Exclusion criteria: :

 Missing informed consent.

 Primary lactose intolerance.

 Concomitant intestinal infection (other than norovirus).

 Subjects with galactosemia or patients requiring a low galactose diet.

 Age < 18 years.


Intramuscular Diclofenac in the Prevention of Post-ERCP Pancreatitis

Summary: Pancreatitis is one of the major complications of ERCP. It has been shown that NSAIDs are potent inhibitors of phospholipase A2, activity which is increased in pancreatitis. The only one study with IM diclofenac showed reduction of post-ERCP pancreatitis without SOD (sphincter of Oddi dysfunction) by subgroup analysis in small study population. Therefore the investigators must need large scaled randomized control study including of SOD.
Inclusion criteria: inclusion criteria:

 Consecutive patients were recruited for the study who presented to the Yonsei University Medical Center with variable symptom or cause for ERCP older than 20 years.

Exclusion criteria: :

 Patients were excluded from study participation if:

 they had a contraindication for diclofenac,

 including patients with recently diagnosed peptic ulcer disease or active/recent gastrointestinal hemorrhage within 4 weeks,

 renal failure (Cr > 1.4),

 those who had taken an NSAID during the preceding week (ASA 325 mg daily or less acceptable),

 those who developed acute pancreatitis during the 2 weeks before ERCP,

 those with a history of chronic calcific pancreatitis or allergy to aspirin or NSAID, and

 those who did not agree intramuscular injection. Additionally, if state of patients was intrauterine pregnancy or breast feeding mother, they were excluded. Finally, patients were excluded for study if they had bleeding tendency and contraindication for intramuscular injection.


Comparison Between Open and Laparoscopic Splenic Aneurysms Repair

Summary: The purpose of this study is compare two different surgical treatments of splenic artery aneurysms: open and laparoscopic approach.
Inclusion criteria: inclusion criteria:

 Splenic artery aneurysm with diameter greater than 2 cm

 Splenic artery aneurysm with diameter smaller than 2 cm if risk factors for rupture are associated (child bearing age, pregnancy, blister or saccular shape, increasing diameter)

Exclusion criteria: :

 Complex aneurysm involving the celiac trunk

 American Society of Anesthesiologists (ASA) Score > 3

['Laparoscopic splenic aneurysm repair, eventual splenectomy', 'Laparotomic splenic artery aneurysm repair, eventual artery reconstruction or splenectomy']


Oxidative Stress and Hemodialysis Access Failure

Summary: Complications of hemodialysis access are the most frequent single reason for hospitalization among patients with End Stage Renal Disease (ESRD). Uremia, and particularly uremia in patients with diabetes, is a state of increased oxidative stress. The central hypothesis to be tested by this project is that oxidative stress is a major (and modifiable) trigger for vascular access complications. We hope to slow or reduce rates of stenosis, thrombosis and access complications by giving Vitamin E supplementation to patients being treated by hemodialysis.
Inclusion criteria: inclusion criteria:

 Adults, end stage renal disease treated by hemodialysis, patent hemodialysis vascular access (graft or fistula)

Exclusion criteria: :

 Temporary catheter dialysis access, inability to be compliant with study medication

['End Stage Renal Disease', 'Hemodialysis']


Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression

Summary: Hormonal treatment of perimenopausal women has frequently utilized oral contraceptive pills (OCPs). Because of their ability to suppress ovulation and establish cycle control, OCPs have become a popular option, and one that is FDA approved for use until menopause. However, use of OCPs in women in their 40's and 50's carries significant cardiovascular risks. Venous thromboembolism risk is 3-6 fold greater in OCP users, and the risk of myocardial infarction (MI) is approximately doubled in OCP users over the age of 40. This occurs at an age where the background population risk of MI begins to increase, such that the absolute number of cases rises substantially. Women with additional risk factors for cardiovascular disease have a much greater risk for MI (6-40-fold) in association with OCPs. There are also large subgroups of midlife women who are not candidates for OCP use, such a smokers and migraineurs. Moreover, the trend towards lower estrogen dosing with OCPs containing 20 micrograms of ethinyl estradiol has not led to a detectable decrease in thromboembolic risk.~Because of their increased potential risks, it is appropriate to seek alternatives to OCPs and to explore lower doses of hormones to relieve perimenopausal symptoms that occur prior to a woman's final menses. Recent evidence indicates that the hypothalamic-pituitary axis of reproductively aging women is more susceptible to suppression by sex steroids that previously believed. It is possible that hormone doses as low as 50 micrograms of transdermal estradiol (TDE) can suppress the hypothalamic-pituitary axis of midlife women. It is also tempting to speculate that the low but measurable circulating doses of levonorgestrel that are present when a woman uses the Mirena intrauterine system (IUS) can contribute to or even independently suppress the hypothalamic-pituitary axis, and reduce the hormonal fluctuations that result in worsening of perimenopausal symptoms. The combination of low dose TDE plus Mirena may therefore confer superior symptom control as well as contraceptive effectiveness, at far less risk.
Inclusion criteria: inclusion criteria:

 Age 40-52

 History of regular menstrual cycles every 20-35 days in mid-reproductive life (20-35 years of age)

 At least 1 period within the past 3 months

 BMI less than 35 kg/m2

 Presence of at least one of the following perimenopausal symptoms:

 Hot flashes (vasomotor symptoms)

 Cyclical headache, bloating or adverse mood

 Self-reported poor quality of sleep

Exclusion criteria: :

 Age < 40 years

 Hysterectomy or bilateral oophorectomy

 Cigarette smoking

 Signs or symptoms of restless leg syndrome or sleep apnea

 Any chronic renal or hepatic disease that might interfere with excretion of gonadotropins or sex steroids

 Moderate/vigorous aerobic exercise > 4 hours per week

 Inability to read/write English

 Pregnant Women

 Prisoners

 Decisionally challenged subjects

 Any medical condition that makes use of Topical estradiol or Mirena contraindicated.

 Sex hormone use within the past 30 days

 History of cancer, blood clots or blood clotting disorder

['Menopausal and Other Perimenopausal Disorders']


Validation of a Delirium Monitor

Summary: Delirium is a common disorder in hospitalized patients, nevertheless it is poorly recognized by physicians and nurses, even when screening instruments are used. Electroencephalography (EEG) appears to be a sensitive tool for the diagnosis of delirium. However, standard EEG recording with 25 electrodes is labor intensive. We have previously showed that a brief EEG registration with three electrodes and automatic processing can distinguish patients with delirium from patients without delirium very well. However, these findings need to be validated in an unselected population.~The primary objective of this validation study is to investigate the sensitivity, specificity, and predictive values of the EEG-based delirium monitor (including three electrodes and a reference electrode) compared to delirium quantification in frail elderly patients after surgery.~In an international multicenter study, 154 frail elderly patients will be included who will undergo elective surgery and are expected to remain admitted for at least two postoperative days. Patients are excluded if communication is not possible or admitted for neurological surgery.~A five minute EEG registration with the delirium monitor with four electrodes will be performed prior surgery and three consecutive days after surgery or until discharge. Within one hour of the EEG recording, the delirium assessment will be performed and recorded on video, which will be evaluated by delirium experts. The relative delta power (calculated from one minute of artifact-free EEG segment) will be compared with the conclusion of the delirium experts.
Inclusion criteria: inclusion criteria:

 60 years and older

 Frail

 Undergoing elective surgery

 Expected to remain admitted for at least 2 postoperative days

Exclusion criteria: :

 No communication possible due to a language barrier or deafness

 Admission for neurological surgery

 Participation in this study during a previous hospital admission

 Practical or logistical reasons hampering the use of the delirium monitor, such as technical failure of the monitor

 Isolation because of known carrier ship of a resistant bacterium


A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

Summary: This is a study to determine the safety and efficacy of the drug, mebendazole, when used in combination with standard chemotherapy drugs for the treatment of pediatric brain tumors. Mebendazole is a drug used to treat infections with intestinal parasites and has a long track record of safety in humans. Recently, it was discovered that mebendazole may be effective in treating cancer as well, in particular brain tumors. Studies using both cell cultures and mouse models demonstrated that mebendazole was effective in decreasing the growth of brain tumor cells.~This study focuses on the treatment of a category of brain tumors called gliomas. Low-grade gliomas are tumors arising from the glial cells of the central nervous system and are characterized by slower, less aggressive growth than that of high-grade gliomas. Some low-grade gliomas have a more aggressive biology and an increased likelihood of resistance or recurrence.~Low-grade gliomas are often able to be treated by observation alone if they receive a total surgical resection. However, tumors which are only partially resected and continue to grow or cause symptoms, or those which recur following total resection require additional treatment, such as chemotherapy. Due to their more aggressive nature, pilomyxoid astrocytomas, even when totally resected, will often be treated with chemotherapy. The current first-line treatment at our institution for these low-grade gliomas involves a three-drug chemotherapy regimen of vincristine, carboplatin, and temozolomide. However, based on our data from our own historical controls, over 50% of patients with pilomyxoid astrocytomas will continue to have disease progression while on this treatment. We believe that mebendazole in combination with vincristine, carboplatin, and temozolomide may provide an additional therapeutic benefit with increased progression-free and overall survival for low-grade glioma patients, particularly for those with pilomyxoid astrocytomas.~High grade gliomas are more aggressive tumors with poor prognoses. The standard therapy is radiation therapy. A variety of adjuvant chemotherapeutic combinations have been used, but with disappointing results. For high-grade gliomas this study will add mebendazole to the established combination of bevacizumab and irinotecan to determine this combinations safety and efficacy
Inclusion criteria: inclusion criteria:

 Age > 1 year of age and ≤ 21 years of age

 Diagnosis

 2.1. Group A - Low-grade Glioma Group:

 Histology: Biopsy-proven:

 Pilocytic Astrocytoma

 Fibrillary Astrocytoma

 Pilomyxoid Astrocytoma

 Pleomorphic Xanthoastrocytoma

 Other low grade astrocytomas

 Children with optic pathway tumors must have evidence of progressive disease on MRI and/or symptoms of deteriorating vision or, progressive hypothalamic/pituitary dysfunction or, diencephalic syndrome or precocious puberty.

 Patients with relapsed low-grade gliomas who have been previously treated with chemotherapy will be eligible for the study provided they have not previously failed therapy with any of the chemotherapeutic agents used in this study.

 2.2 Group B - High-grade Glioma/Pontine Glioma Group:

 Histology: Biopsy-proven

 Anaplastic astrocytoma

 Glioblastoma multiforme

 Gliosarcoma.

 Patients with primary spinal cord malignant gliomas are eligible.

 For primary brainstem tumors, histologic verification is not required. Patients are eligible when diagnosed with clinical and radiographic (MRI) evidence of tumors which diffusely involve the brainstem. Patients with tumors which intrinsically (greater than 50% intra-axial) involve the pons or pons and medulla or pons and midbrain or entire brainstem are eligible. Tumors may contiguously involve the thalamus or upper cervical cord.

 Timing of therapy:

 Patients must be enrolled before treatment begins. Treatment must start within 14 days of study enrollment.

 All clinical and laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated in the eligibility section.

 Adequate hematologic, renal, liver function as demonstrated by laboratory values.

 Negative pregnancy test in women of childbearing potential within 7 days of initiating investigational therapy

 Life expectancy ≥ 3 months

 Concurrent medications: It is recommended that patients are weaned off or are on a tapering dose of corticosteroids before starting therapy on study.

 Patient or legal guardian must give written, informed consent or assent (when applicable)

 Recent mothers must agree not to breast feed while receiving medications on study.

Exclusion criteria: :

 Age < 1 year or > 21 years

 Patients who have known allergy to mebendazole or benzimidazole class drugs.

 Patients who have previously had a severe side effect, such as agranulocytosis and neutropenia, in conjunction with previous mebendazole or benzimidazole class drug for a parasitic infection .

 Patients who are taking metronidazole and cannot be safely moved to a different antibiotic greater than 7 days prior to starting mebendazole therapy.

 Pregnant female patients are not eligible for this study. Pregnancy tests with a negative result must be obtained in all post-menarchal females.

 Lactating females must agree they will not breastfeed a child while on this study.

 Males and females of reproductive potential may not participate unless they agree to use an effective contraceptive method and continue to do so for at least 6 months after the completion of therapy.

 Patients who are unable to take oral medications because of significant vomiting will be excluded.

 Group A - Low-grade Glioma Group ONLY:

 Patients who have failed prior chemotherapy with vincristine, carboplatin, or temozolomide for this tumor are excluded.

 Patients with Neurofibromatosis Type 1

 Group B - High-grade Glioma/Pontine Glioma Group ONLY:

 Patients who failed prior chemotherapy with bevacizumab or irinotecan for this tumor are excluded.

 Patients who progressed on or within 12 weeks after completion of radiotherapy are excluded.

 Patients with a history or current condition that would preclude the use of bevacizumab

['Mebendazole', 'Vincristine', 'Carboplatin', 'Temozolomide', 'Bevacizumab', 'Irinotecan']

Mebendazole Vincristine Carboplatin Temozolomide Bevacizumab Irinotecan

['DIPG', 'Pilomyxoid Astrocytoma', 'Pilocytic Astrocytoma', 'Glioma, Astrocytic', 'Optic Nerve Glioma', 'Pleomorphic Xanthoastrocytoma', 'Glioblastoma Multiforme', 'Anaplastic Astrocytoma', 'Diffuse Intrinsic Pontine Glioma', 'Low-grade Glioma', 'Brainstem Glioma', 'Gliosarcoma']

DIPG
Pilomyxoid Astrocytoma
Pilocytic Astrocytoma
Glioma
Astrocytic
Optic Nerve Glioma
Pleomorphic Xanthoastrocytoma
Glioblastoma Multiforme
Anaplastic Astrocytoma
Diffuse Intrinsic Pontine Glioma
Low-grade Glioma
Brainstem Glioma
Gliosarcoma


APACC Study:Prospective Study on Aspirin Efficacy in Reducing Colorectal Adenoma Recurrence

Summary: Experimental and epidemiologic studies have suggested that aspirin intake reduces the risk for colorectal cancer. In the APACC study we randomly assigned 291 patients to daily Aspirin or Placebo for 4 years. However, the available data are not sufficient to serve as the basis for firm recommendations
Inclusion criteria: inclusion criteria:

 Patients are aged between 18 and 75 years At least 3 adenomas irrespective size or at least one measuring 6mm or more All subjects had a clean colon at the study entry

Exclusion criteria: :

 No personal history of colon cancer, no inflammatory bowel disease, no familial adenomatous polyposis, no regular use of aspirin


OPUS School Meal Study - Cross Sectional Analyses From Baseline Investigations

Summary: The present study is based on cross-sectional data from the baseline investigations carried out in OPUS School Meal Study - a randomized crossover study carried out in 9 primary schools in Denmark 2011-2012. Approximately 800 Danish school children from 3rd and 4th grades (8-12 year olds) took part in these baseline investigations of socioeconomic status, pubertal status, growth status, learning abilities, well-being, sleep, physical activity and risk markers of Cardiovascular Disease (CVD), type II diabetes and osteoporosis.
Inclusion criteria: inclusion criteria:

 Pupils in 3rd and 4th grades

 Primary Schools in the Zealand Region and Capital Region of Denmark Schools with an available school kitchen, that can be approved by the food authorities

 Schools where at least 60 % of the pupils in three or more classes signs up to participate in the Study

Exclusion criteria: :

 The children should not participate in a scientific study or have participated in a scientific study within the last 4 weeks. This, however depends on the character of the other study.

 The children must not suffer from serious food allergies or food intolerance.

 The children must not suffer from diseases or conditions that makes them ill-suited for participation in the study, eg. malabsorptive conditions or serious mental disorders

 The schools must not offer an well-established common meal plan, that provides most of the pupils with healthy food on a daily basis


MISSION COPD - Modern Innovative SolutionS in Improving Outcomes iN COPD

Summary: MISSION is a new and novel way of delivering highly specialised Chronic Obstructive Pulmonary Disease (COPD) care and has the potential to change the way COPD care across the UK is delivered as well as services for other long term health conditions. The MISSION model has been piloted in asthma which is the subject of an ongoing research study. This is the first model of this type in COPD and the current research study aims to evaluate the outcomes of the project. This will be done in several different ways. The study is a mixed methods evaluation of the new service comparing outcomes before and after the clinic using retrospective data analysis and prospective qualitative interview. The study will be conducted at Portsmouth Hospitals NHS Trust and will recruit patients who attend MISSION COPD clinics as well as staff who attended MISSION clinics in a professional capacity.
Inclusion criteria: inclusion criteria - Patients:

 Male of Female, aged 18 years or above.

 Attended the MISSION clinic as a patient.

 Participant is willing and able to give informed consent for participation in the study.

Exclusion criteria:  - Patients:

 - The patient is unable or unwilling to give consent

 inclusion criteria - Health Care Professionals

 Male or Female, aged 18 or above.

 Attended the MISSION clinic as a health care professional

 Participant is willing and able to give informed consent for participation in the study.

['Pulmonary Disease, Chronic Obstructive']


Study Comparing Rifaximin With Xifaxan 200 mg in Traveler's Diarrhea

Summary: The primary objective is to demonstrate rifaximin 200 milligrams (mg) tablets (test) and Xifaxan® 200 mg tablets (reference) are clinically bioequivalent with respect to the clinical cure rates when administered 3 times a day (TID) for 3 days in participants with travelers' diarrhea.
Inclusion criteria: inclusion criteria:

 Adult male or nonpregnant female aged ≥18 years non-indigenous travelers (for example; visiting students/faculty or international tourists) affected by naturally acquired acute diarrhea. Diarrhea is defined as the passage of at least 3 unformed stools in a 24-hour period. Stools are classified as formed (retains shape), soft (assumes shape of container), or watery (can be poured). When using this classification, both soft and watery stools are unformed and abnormal.

 At least 3 unformed stools recorded within the 24 hours immediately preceding randomization.

 At least 1 of the following signs and symptoms of enteric infection:

 abdominal pain or cramps

 nausea

 vomiting

 fecal urgency

 excessive gas/flatulence

 tenesmus

 Women of child-bearing potential have a negative pregnancy test prior to beginning therapy and agree to use effective contraceptive methods during the study.

Exclusion criteria: :

 Pregnant, breast feeding, or planning a pregnancy.

 Immediately prior to randomization, acute diarrhea for >72 hours.

 Presence of:

 fever (≥100 degrees fahrenheit [°F] or ≥37.8 degrees celsius [°C]), or

 hematochezia (blood in stool), or

 clinical findings suggesting moderate or severe dehydration.

 Active, uncontrolled, or clinically significant diseases or disorders of the heart, lung, kidney, gastrointestinal (GI) tract (other than infectious diarrhea in travelers), or central nervous system.

 Administration of any of the following:

 any antimicrobial agents with an expected activity against enteric bacterial pathogens within 7 days preceding randomization

 more than 2 doses of a symptomatic antidiarrheal compound such as antimotility agents, absorbent agents, and antisecretory agents within 8 hours preceding randomization

 Use of any drug such as aspirin or ibuprofen (Advil), which can cause GI bleeding. Acetaminophen (Tylenol) or paracetamol is acceptable.

['Rifaximin', 'Xifaxan®', 'Placebo Tablet']


Opioids Withdrawal Syndrome in Critically Ill Patients: a Multicenter Prospective Cohort Study

Summary: Critically ill patients who are mechanically ventilated may require prolonged administration of sedatives and analgesics. Their prolonged use has been associated with withdrawal symptoms upon rapid weaning in critically ill patients. These withdrawal symptoms may be associated with adverse clinical outcomes. Although well studied in the paediatric population, little is known about the epidemiology, risk factors and optimal screening methods in adults. Studying this problem is essential as we strive to develop proper weaning strategies.~Methods: Prospective observational two-center study in critically ill adult patients Objectives: 1) Describe the incidence of iatrogenic withdrawal of sedatives and analgesics in critically ill adult patients and 2) Evaluate the performance of screening tools assessing withdrawal that were developed for the paediatric patient in the adult population.
Inclusion criteria: inclusion criteria:

 intermittent use or continuous infusion opioids for at least 96 hours

Exclusion criteria: :

 Patient and/or relatives unable to communicate in French or English

 Patients unable to communicate (consent form and evaluation)

 Patient deaf without appropriate hearing aid

 Patients unable to communicate (consent form and evaluation)

 Imminent and predictable death according to medical team

 Severe brain injury, defined as Glasgow Coma Scale (GCS) score of 8 or less at ICU admission

 Moderate brain injury, defined as GCS between 9 and 12, with elevated intracranial pressure (ICP > 20 mm Hg) who requires ICP monitoring and osmotherapy

 Major confounding factors for withdrawal syndrome by causing shivering, sympathetic drive and autonomic disorders

 Underlying active neurological condition (status epilepticus, encephalopathy, hypoxia)

 Neurological problems are covariates, which would make the assessment of sedation or IWS difficult Patient previously included in the study at any of the two hospitals (readmission to the ICU at a later date during the period of recruitment for the study, limiting to 1 weaning episode per patient)

 Thoracic and cervical spinal cord injury

 Adrenergic response to pain will be difficult to assess

 Unable to assess validated tool: DSM-V, RASS, CAM-ICU

 Narcotic

 If the underlying neurological condition resolves within the 96 hours, the patient may be included in the study

 Substance abuse prior to ICU admission (28)

 Chronic alcohol use defined as alcohol consumption of more than 2 drinks per day and/or more than 14 drinks per week for men and 9 drinks per week for woman as reported by family or as per patient's medical record


The Analgesic Effect of Combined Nerve Block and Systemic High Dose Glucocorticoid After Total Knee Arthroplasty.

Summary: Purpose:~The purpose of this study is to evaluate the postoperative analgesic effect of a combined Saphenous nerve block and Obturator nerve block with local infiltration analgesia in the tissue around the knee after total kneearthroplasty. In the combined nerve blocks we use a mixture of Ropivacaine and Adrenaline combined with high dose systemic dexamethasone and Ketorolac and the mixture for local infiltration consist of Ropivacaine, Adrenaline and Ketoroloc. The investigators hypothesis is that the combined nerve blocks reduces pain and reduces the opioid consumption and thus reduce side effects such as nausea, vomiting and lethargy compared to the current treatment with local infiltration analgesia.~Background:~Nerve blocks as analgesic treatment after orthopedic surgery is a recognized and proven procedure. The nerve blocks have the disadvantage that not only do they anesthetize the sensory nerve fibers but also the nerve fibers to the muscles of the leg. The Saphenous nerve block causes only stunning of sensory nerves to the knee region. The Obturator nerve block causes both stunning of the sensory nerves to the knee region and the thighs inward leading muscles, and does not affect the patient's mobilization capacity.~Both blocks are known to be a good addition to the analgesic treatment. Ropivacaine is a well-known local anesthetic. Adrenaline have also been used in other studies, in addition to the local anesthetic agent, and has been shown to prolong the effect of the nerve block. Saphenous and Obturator nerve block with all four drugs Ropivacaine and Adrenaline combined with high dose systemic Dexamethasone has not been systematically investigated in knee replacement surgery, and it is not known whether this method will provide better pain treatment.~Method~The patient can receive one of two treatments, determined randomly:~A. Saphenous and Obturator nerve block with active anesthetics (Ropivacaine, Adrenaline) combined with systemic ketoroloc and high dose Dexamethasone and local infiltration around the knee joint with placebo medicine (normal saline).~B. Both blocks with placebo medicine (normal saline) and local infiltration around the knee joint with activ local anesthetic.~Neither patient, investigator or staff around the patient will have knowledge of which treatment the patient has received.~The blocks will be placed before the operation and local infiltration around the knee joint will be given by the surgeon during the operation.
Inclusion criteria: inclusion criteria:

 Age> 50 years

 Patients set to cemented Total knee arthroplasty in spinal block

 ASA 1-3

Exclusion criteria: :

 Patients who can not cooperate with the investigation

 Patients who have given written informed consent to participate in the study after having understood the contents of the protocol and limitations fully

 Patients who do not understand or speak Danish

 Patients receiving immunosuppressive therapy

 Patients receiving glucocorticoid daily

 Patients with a treatment-dependent diabetes mellitus

 Patients with known neuropathy in the lower limbs

 Allergy to those used in the study drugs

 Alcohol and / or drug abuse - the investigator's opinion

 Patients who can not tolerate NSAIDs

 Fixed several times daily consumption of strong opioids (morphine, ketogan, Oxynorm, methadone, fentanyl)


Efficacy of Suvorexant to Treat Insomnia Related to Bipolar Disorder

Summary: The purpose of this study is to evaluate the efficacy of suvorexant, added to existing medications, for treatment-resistant insomnia in individuals with bipolar disorder. The investigators hypothesize that participants receiving suvorexant for one week will experience significantly greater improvement in sleep duration compared to participants receiving placebo.
Inclusion criteria: inclusion criteria:

 Adult outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder (296.70), bipolar II disorder (296.89), or bipolar disorder not otherwise specified (296.80), with concurrent insomnia related to bipolar disorder (307.42).

 Currently taking ≥ 1 prescription psychotropic medication (hypnotic agents, anxiolytics, atypical antipsychotics, mood stabilizers, and/or antidepressants) for management of bipolar disorder.

 Subjective total sleep time (sTST) < 6 hours on ≥ 1 night during the prior week.

Exclusion criteria: :

 Current hypo/manic symptoms, as evidenced by the Young Mania Rating Scale (YMRS) total score ≥ 12.

 Current (past 6 months) alcohol or substance use disorder.

 Current psychosis.

 Patients who are actively suicidal or evaluated as being a high suicide risk.

 Women who are currently pregnant or breastfeeding.

 Clinically significant abnormalities on baseline laboratory tests (comprehensive metabolic panel, fasting lipid panel, Complete Blood Count (CBC) with differential, thyroid stimulating hormone).

 Presence of any unstable and/or potentially confounding neurological and/or medical disorder.


Prevention of Bacterial Infections in Newborn

Summary: The last decade has witnessed an important reduction of the mortality in children under 5 years but such reduction has not impacted in neonates. Mortality in neonates contributes 40% of all deaths occurring in children below 5 years of age.~Severe bacterial disease is among the leading causes of neonatal deaths. Bacterial disease follows bacterial infection. Individuals can be infected without developing disease (carriage stage) but infection is needed to subsequently develop disease. In sub-Saharan Africa, bacterial carriage (i.e. in the birth canal and/or nasopharyngeal tract) is very common in all age groups, with the consequence that occurrence of bacterial disease is one of the highest in the world.~Newborns can be infected during labour - when passing through the birth canal - and during the first days/weeks of life, as a consequence of the close physical contact with the mother, if the latter carries bacteria in the nasopharyngeal tract.~If the mother is an important source of bacterial infection to the newborn, treating mothers with a powerful antibiotic during labour should decrease bacterial carriage and therefore diminish the risk of bacterial transmission to the newborn during the first days/weeks of life, which should in turn result in the lower occurrence of severe bacterial disease and hence lower mortality.~The purpose of this trial is to evaluate the impact of a single oral dose of azithromycin given to women in labour on bacterial carriage of the newborn as well as the women during the first month after delivery.~The investigators have selected an antibiotic (azithromycin) that in sub-Saharan Africa has already shown both a strong impact on bacterial nasopharyngeal carriage and on all-cause mortality when administered to everybody in a community (mass drug administration). This specific antibiotic has several advantages for being deployable as a simple intervention in rural Africa, i.e. it requires a single oral administration, it has no special storage requirements and it has the potential to eliminate many of the bacteria commonly causing severe disease in newborn.~This clinical trial will be conducted in a peri-urban health facility in Western Gambia. If an impact is shown, the next step would be to conduct a larger study aiming at establishing if the intervention, implemented at a lower level of care (most African women deliver at home assisted by traditional birth assistants), decreases the occurrence of neonatal bacterial disease
Inclusion criteria: inclusion criteria:

 Pregnant women (aged 18 to 45 years)

 in labour

 attending a health centre in western Gambia for delivery

Exclusion criteria: :

 Known HIV infection.

 Any chronic or acute conditions of the women that might interfere with the study as judged by the research clinician.

 Planned travelling out of the catchment area during the following 2 months (follow-up period)

 Planned caesarean section

 Known required referral

 Known multiple pregnancy

 Known severe congenital malformation

 Intrauterine death confirmed before randomization

 Known allergy to macrolides

 Consumption of antibiotic within the week before randomisation


LigaSure Small Jaw® Versus Conventional Neck Dissection in Head and Neck Cancer Patients

Summary: The aim of this prospective randomized study was to investigate if the LigaSure vessel sealing system can reduce the operation duration and the postoperative drainage amount in patients undergoing neck dissection.
Inclusion criteria: inclusion criteria:

 Patients aged 20 to 80 years scheduled to receive neck dissection due to head and neck cancer

Exclusion criteria: :

 history of coagulation disorders

 prior radiation to the neck

 prior neck dissection

 declined to participate


Are There Protective Effects of Antioxidants, Calcium Channel Blocker and Angiotensin Receptor Blocker Against Extracorporeal Shockwaves Lithotripsy Induced Renal Injury?

Summary: This study will be conducted to evaluate the protective effects and mechanisms of antioxidants (vitamins A, C, E and Selenium), calcium channel blocker (Verapamil) and angiotensin receptor blocker (Lozartan) against shock wave induced renal injuries.
Inclusion criteria: inclusion criteria:

 Well functioning kidney (serum creatinine <1.2 mg/dl).

 Solitary renal stone.

 Size: 25 mm or less in the largest diameter.

Exclusion criteria: :

 Contraindications to ESWL

 Previous surgical treatment of renal stones.

 Congenital renal anomalies.

 Pediatric patients (age <18 years).

 Patients with Diabetes or hypertension

['Antioxidant group', 'Calcium Channel Blockers', 'Angiotensin receptor blocker group', 'Placebo']

Antioxidant group
Calcium Channel Blockers
Angiotensin receptor blocker group
Placebo


Geographic Influences on Appendicectomy Outcomes

Summary: Introduction~Appendicitis is a common condition which represents a significant resource burden for the Scottish National Health Service (NHS). It is unknown whether there are significant differences in outcomes following appendicectomy which may be explained by geographic factors.~Aims~The aim of this study is to describe appendicectomy outcomes in Scotland as they vary by the urban-rural nature of the patient's home location and travel time from hospital.~Methods~This research study is a retrospective observational enquiry which will utilise administrative data from the Information Services Division (ISD) of NHS National Services Scotland. Patient episodes will be identified by a procedure code for appendicectomy, and the urban-rural classification of patients will be derived from postcode data. Travel time from hospital will also be estimated through postcode data. The investigators will study a 10 year period from January 2001 to December 2010.~Primary outcome measures will be risk-adjusted 30 day/inpatient mortality, 30 day readmission rate, 30 day re-operation rate, length of stay and negative appendicectomy rates.
Inclusion criteria: inclusion criteria:

 All patients, of all ages, undergoing appendicectomy (OPCS code H01) during the time period January 2001 - December 2010.

Exclusion criteria: :

 Patients undergoing appendicectomy for whom this is incidental to a more major abdominal procedure.

 Patients non-resident in Scotland.


Jump Step - A Participatory Approach to Physical Activity & Mental Wellness

Summary: The WHO, the Pan American Health Organization, the EU Council of Ministers, the World Federation of Mental Health, and the UK Royal College of Psychiatrists all agree -there can be no health without mental health. Within Canada, 6.7M people live with a mental illness and when family and caregivers are included almost everyone is affected.~A systematic review (2014) concluded that physical activity has a significant potential for reducing depressive symptoms in people with a mental illness. Globally, physical inactivity is pandemic. Current guidelines recommend a minimum of only a 150 minutes a week of moderately vigorous exercise but 85% of Canadians do not meet the national recommendations. How then can people with depression be motivated to become physically more active?~Group Medical Visits (GMVs) can be used to provide health services and they have proven effective in some settings, including mood disorders. As well as providing economic and resource efficiencies, the GMV model has the potential to add a 'support group/accountability' element for behavioural interventions such as physical activity promotion; such influence is not present in an individual patient-physician consultation.~Jump Step is a 14-week program within a GMV setting designed to motivate and support people with depression to engage in regular physical activity. The investigators seek to design, implement, and evaluate the effectiveness of the Group Medical Visits focused on promoting physical activity for patients with depression.
Inclusion criteria: We will recruit up to 80 participants who

 inclusion criteria:

 are adults (≥18yrs)

 have a confirmed psychiatric assessment of Major Depressive Disorder (MDD) and/or Bipolar II, depressive

 are of moderate or higher severity (PHQ-9 >14)

 are community-dwelling and able to attend Group Medical Visits in the Lower Mainland

 are able to comply with scheduled visits, treatment plan, and other procedures;

 read, write, and speak English with acceptable auditory and visual acuity

 provide signed/dated informed consent; and

 able to walk independently.

Exclusion criteria: :

 Active psychotic symptoms

 a primary active diagnosis of substance abuse.

 Participants will need to have a working proficiency in English as group discussions, accompanying texts, and instructions will all be in English. To provide adequate translation services for these elements in one or more other languages is beyond our budget and may also influence the dynamics of the GMV. It could be considered in a future iteration of this research program.

['Major Depressive Disorder', 'Bipolar, Depression']

Major Depressive Disorder
Bipolar
Depression


Rifampicin Explorative PK Study for Tuberculous Meningitis Comparing Oral and Intravenous Preparation

Summary: Tuberculous (TB) meningitis is the most severe manifestation of TB infection, leaving up to 50% of patients dead or neurologically disabled. Current treatment is similar to treatment of lung TB, although penetration of some antibiotics into the brain is poor and the immune-pathology of TB meningitis is very different from pulmonary TB. In a recent phase II clinical trial from the investigators group, the first of its kind globally, intensified antibiotic treatment, with moxifloxacin and high dose rifampicin, strongly reduced mortality of TB meningitis.~The investigators aim to examine the effect of intensified antibiotic treatment on mortality and morbidity of TB meningitis in a phase 3 clinical trial, preceded with an explorative pharmacokinetic (PK) study to examine if higher oral doses rifampicin result in exposures similar to the i.v. dose used in our phase 2 trial, since oral rifampicin could be implemented much easier in low-resource settings.
Inclusion criteria: inclusion criteria:

 Age 18 years or older

 Probable/possible tuberculosis meningitis using uniform case definition

 Agree to participate in the study

Exclusion criteria: :

 Patient with antituberculosis treatment within last 2 weeks.

 Increase liver function >5x upper limit of normal

 Pregnancy

['Rifampicin intravenous', 'Oral rifampicin']


Lateral Cord Stimulation as a New Treatment for Refractory Spastic Cerebral Palsy

Summary: The aim of our work is to investigate whether electrical Lateral Cord Stimulation (LCS) causes an inhibitory and modulatory action by indirect cerebellar activation, so releasing spasticity and the spastic syndrome in selected cases of patients with cerebral palsy
Inclusion criteria: inclusion criteria:

 Aged sixteen or older

 Spastic Cerebral Palsy with stable condition

 Motor disability unilateral or predominantly unilateral.

 Troubles of speech clinically evident.

 Normal or Slightly sub-normal I.Q

 No psychiatric disorders.

Exclusion criteria: :

 Severe cardiac or respiratory troubles

 Fixed abnormal postures (except if previously corrected by orthopedic surgery)

 Chronic recurrent bronchial or pulmonary infections

 Chronic recurrent urinary infections

 Severe osteoporosis on affected limbs

 Chronic skin ulcerations.

['Lateral spinal cord surgical implant of electrodes']


Efficacy and Safety of 5 mg Sublingual Zolpidem vs 10mg Oral Zolpidem in the Induction and Maintenance of Sleep in Patients With Primary Insomnia

Summary: The purpose of this study is to evaluate the efficacy and safety of sublingual zolpidem presentation 5 mg in the induction of sleep in patients with primary insomnia.
Inclusion criteria: inclusion criteria:

 Men or women aged between 20 and 64 years;

 Diagnosis of primary insomnia according to criteria defined by DSM-IV;

 Difficulty in maintaining sleep and waking up until 3 am;

 Not having used any psychoactive drug in the last 30 days prior to their inclusion in the study;

 Signature of IC.

Exclusion criteria: :

 Previous history of serious medical illness, neurological or psychiatric disorder;

 Allergy or hypersensitivity to zolpidem;

 Obstructive Sleep Apnea syndrome;

 Polysomnography with apnea and hypopnea index >10/hour or PLM >15/h;

 Other secondary sleep disorders;

 History of substance abuse or dependence;

 History of daily consumption of alcoholic beverages;

 Pregnancy, lactation or refusal to use safe contraceptive methods during the study.


Randomized, Placebo-controlled Multicenter Trial of Lithium Plus Treatment as Usual (TAU) for Acute Suicidal Ideation and Behavior in Patients With Suicidal Major Depressive Episode

Summary: The primary hypothesis of this confirmatory study is that lithium therapy will acutely decrease suicidal ideation and/or suicidal behaviour in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behaviour over 5 weeks in inpatients with MDE.
Inclusion criteria: inclusion criteria:

 Major depressive episode; inpatient at screening visit; suicidal ideation/behaviour present defined by a clinical rating of 8 on the Sheehan Suicidality Tracking Scale (S-STS) and a rating of ≥20 on the Montgomery Asberg Depression Scale (MADRS) at both screening and baseline visits; both gender, age 18 years.

Exclusion criteria: :

 Contraindication for and history of lithium treatment within the past 6 months; patient unable to tolerate lithium treatment in the past; comorbid borderline/antisocial personality disorder, currently active substance dependency; patients with acute or unstable severe medical conditions, patients unable to understand the informed consent or involuntary inpatients, positive toxicology screen (illegal drugs), pregnancy and lactation


TBE Antibody Persistence and Booster Vaccination Study in Adults (Follow-up to Study 223)

Summary: The purpose of this study is to assess:~TBE antibody persistence 24, 34, 46 and 58 months (as applicable) after the first booster TBE vaccination with FSME-IMMUN 0.5ml given in Study 223, by means of ELISA (IMMUNOZYM FSME IgG) and Neutralization test (NT),~TBE antibody response to a second booster vaccination with FSME-IMMUN 0.5ml in the present study, by means of ELISA and NT,~Safety of FSME-IMMUN 0.5ml after the second booster vaccination.
Inclusion criteria: inclusion criteria:

 Subjects who participated in Study 223 will be eligible for participation in this study if:

 they understand the nature of the study, agree to its provisions and provide written informed consent

 they received the first booster vaccination with FSME-IMMUN 0.5ml during the course of study 223

 blood was drawn after their first booster vaccination in Study 223.

Exclusion criteria: :

 Subjects will be excluded from participation in this study if they:

 received any TBE vaccination since their first booster vaccination with FSME-IMMUN 0.5ml

 have a history of infection with or vaccination against other flaviviruses (e.g. dengue fever, yellow fever, Japanese B-encephalitis) since their first booster vaccination with FSME-IMMUN 0.5ml

 are known to be HIV positive (a special HIV test is not required for the purpose of the study) since their first booster vaccination with FSME-IMMUN 0.5ml

 have a known or suspected problem with drug or alcohol abuse (> 4 liters wine / week or equivalent level of other alcoholic beverages).

 Subjects will not be eligible for booster vaccination if they:

 are not clinically healthy, (i. e. the physician would have reservations vaccinating with FSME-IMMUN 0.5ml outside the scope of a clinical trial)

 suffer from a disease (e.g. autoimmune disease) or are undergoing a form of treatment (e.g. systemic corticosteroids) that can be expected to influence immunological functions

 are females of childbearing potential and are pregnant or breastfeeding before the booster vaccination (positive pregnancy test result at the medical examination before the booster vaccination)

 have shown an allergic reaction to one of the components of the vaccine since their first booster vaccination in Study 223

 are simultaneously participating in another clinical trial including administration of an investigational product within six weeks prior to the booster vaccination until the end of the study

 do not agree to keep a Subject Diary.

 Subjects who meet the eligibility criteria, but have a febrile illness (body temperature >= 38.0°C, measured orally) at the scheduled time of vaccination, will not be vaccinated until their body temperature returns to normal.

 Subjects who have been administered any vaccination within 2 weeks prior to the booster vaccination will not be vaccinated until an interval of two weeks has passed.

 If subjects have received antipyretics within 4 hours prior to the scheduled time of vaccination, the vaccination should be performed at a later time.

 If a subject had a tick-bite within 4 weeks of the scheduled booster vaccination, the vaccination shall be delayed such that an interval of 4 weeks has passed since the tick-bite in order to avoid any interference with diagnostic assays in the event of a TBE infection.

 If a subject has donated blood or plasma or has received a blood transfusion or immunoglobulins within 4 weeks of the scheduled booster vaccination, the vaccination shall be delayed until an interval of 4 weeks has passed.

['Tick-Borne Encephalitis (TBE) Vaccine (Inactivated)']


Influence of Amlodipine on the Mortality of Patients With End-Stage Renal Failure

Summary: Patients with end-stage renal failure have a markedly higher mortality because of cardiovascular events in comparison with the normal population. Disorders in the calcium metabolism, such as calcification of the vessel walls, occur very frequently. There are indications that calcium channel blockers are capable of lowering the cardiovascular mortality in patients with end-stage renal failure.~It is intended to carry out a prospective, randomized, double-blind, placebo-controlled, multicenter study in order to find out if the calcium channel blocker amlodipine is able to reduce the mortality of patients with end-stage renal failure.~The investigation will be carried out after suitable explanation and written informed consent in 356 patients aged between 18 and 90 years with end-stage renal failure and chronic haemodialysis treatment. The patients will be randomized to either treatment with amlodipine 10 mg/day or placebo. The occurrence of events will be documented and evaluated prospectively over a period of 30 months.
Inclusion criteria: inclusion criteria:

 End-stage renal disease

 Hemodialysis

 Hypertension

 Written informed consent

Exclusion criteria: :

 Hypotension of less than 90 mmHg systolic

 High-grade aortic stenosis

 Heart failure of NYHA stage III and IV

 Acute myocardial infarction (within the last 4 weeks)

 Acute heart failure

 Known allergy to the medicament amlodipine or other constituents of the medicament

 Severe disorders of liver function

 Pregnancy and breast-feeding


The Affect of a Ventilated Helmet on Physiological Load

Summary: The use of infantry helmets under heavy heat stress conditions, during physical exertion, may hinder the body's ability to effectively dissipate heat from the head area, thereby damaging the soldier's function. Therefore head cooling may potentially enable a longer duration of activity until reaching fatigue. An improvement in function may also be possible.The purpose of this research is to determine the extent of the cognitive and physiological strain caused by wearing a helmet under exertional conditions while exposed to heavy heat stress and to evaluate the effect of a unique ventilation system connected to the helmet on strain reduction.
Inclusion criteria: inclusion criteria:

 healthy civilian volunteers

 aged 21-28

 without known medical illnesses or medication use

Exclusion criteria: :

 the existence of or suspicion of existing cardiac or respiratory disease

 hypertension

 diabetes

 any hormonal disease or any other chronic illness that may inhibit participation in the experiment

 infectious disease 3 days prior to the experiment.


Characterisation of Healthy Volunteers, Asthma and Chronic Obstructive Pulmonary Disease Patients for Inhalation Profile, Pharyngometry, Spirometric Indices and Lung Morphometry

Summary: This is a clinical study, with no investigational product, to characterise the inhalation profiles of healthy volunteers, volunteers with mild, moderate and severe Asthma and volunteers with mild, moderate and severe Chronic Obstructive Pulmonary Disease (COPD), through the novel dry powder inhaler.
Inclusion criteria: inclusion criteria:

 A subject will be eligible for inclusion in this study only if all of the following criteria apply.

 All volunteers must be aged between 21 to 70 years inclusive and be competent to understand and give informed consent.

 All female volunteers of child bearing potential must have provided a negative pregnancy test before inclusion and prior to any HRCT scan.

 Body weight < 120 kg and BMI within the range 18 - 35 kg/m2 (inclusive).

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

 Available to complete the study

 Subject will then be included only if they fulfil all criteria for the following relevant cohort Healthy: Cohort

 Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history and physical. A subject with a clinical abnormality or parameters outside the reference range for the population being studied may be included if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

 Non-smokers (never smoked or not smoking for >12 months with <1 pack year history) (Pack years = (cigarettes per day smoked/20) x number of years smoked))

 No history of a chronic respiratory disorder.

 No history of acute respiratory disease within four weeks prior to inclusion.

 No history of breathing problems such as a history of asthma, unless the asthma was in childhood and has now completely resolved, no longer requiring maintenance or intermittent therapy.

 No other significant medical disorder that may affect the respiratory system or that causes significant disability.

 Asthmatic: Cohort

 Clinically diagnosed with asthma, for at least 6 months, stratified as either: mild, moderate or severe, based on current treatment, using the British Thoracic Society - - Guidelines on Asthma [BTS, 2009]. For inhaled steroid equivalence to budesonide please refer to the GINA guidelines [GINA, 2008]

 Mild, defined Step 1 or 2 by BTS Asthma Guidelines

 Moderate, defined as step 3 by BTS Asthma Guidelines

 Severe, defined as step 4 or 5 by BTS Asthma Guidelines

 Non-smokers (never smoked or not smoking for >12 months with <1 pack year history (Pack years = (cigarettes per day smoked/20) x number of years smoked))

 Able to withhold from short acting bronchodilators for 6 hours and long acting bronchodilators for 12 hours before study assessments

 No history of acute respiratory disease within four weeks prior to inclusion.

 No history of any other inflammatory lung condition or carcinoma of the lung.

 No exacerbation of disease requiring hospitalisation within previous four weeks.

 COPD: Cohort

 - Clinically diagnosed COPD, for at least 6 months prior to screening, either: mild, moderate or severe/very severe (stage I, II, III/IV) COPD as defined by GOLD guidelines [GOLD 2008]. The following lung function criteria are post bronchodilator

 Stage I:

 Mild COPD. FEV1/FVC < 70%, FEV1 ≥ 80% predicted with or without chronic symptoms (cough, sputum production) Stage II

 Moderate COPD. FEV1/FVC < 70%. 50% ≤ FEV1 < 80% predicted with or without chronic symptoms (cough, sputum production) Stage III and IV

 Severe COPD. FEV1/FVC < 70%. 30% ≤ FEV1 < 50% predicted with or without chronic symptoms (cough, sputum production)

 Very Severe COPD.FEV1/FVC < 70%, FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure

 Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (Pack years = (cigarettes per day smoked/20) x number of years smoked)).

 No history of acute respiratory disease within four weeks prior to inclusion

 No history of any other inflammatory lung condition or carcinoma of the lung.

 No exacerbation of disease requiring hospitalisation within previous four weeks.

 Able to withhold from short acting bronchodilators for 6 hours and long acting bronchodilators for 12 hours before study assessments

Exclusion criteria: :

 A subject will not be eligible for inclusion in this study if any of the following criteria apply:

 As a result of the medical interview, physical examination or screening investigations, the physician responsible considers the volunteer unfit for the study.

 Any pregnant female

 Volunteers who have a past or present disease, which as judged by the Investigator, may affect subject safety or influence the outcome of the study.

 The subject has received an investigational drug or participated in any other research trial within 30 days or five half-lives, or twice the duration of the biological effect of any drug (whichever is longer).

 The subject that has both asthma and COPD.

 Previous inclusion in a research and/or medical protocol involving nuclear medicine,

 Any Radiological investigations with significant radiation burden (a significant radiation burden being defined as ICRP category IIb or above: No more than 10 mSv in addition to natural background radiation, in the previous 3 years including the dose from this study).

 The subject has a history of alcohol or drug abuse.

 The subject has had a respiratory tract infection within four weeks of the start of the study.

 The subject has a history of claustrophobia.

 The subject is unable to perform the Multi Channel Recorder and/or Pharyngometry assessments correctly.

 The subject has a known allergy or hypersensitivity to milk protein.

 Unwillingness or inability to follow any of the procedures outlined in the protocol.

 Subject is kept under regulatory of judicial order in an institution.

 Subject is mentally or legally incapacitated.


Evaluation of the Use of Levemir® in Insufficiently Controlled Patients With Type 1 or Type 2 Diabetes

Summary: This study conducted in Europe. The aim of this study is to evaluated the use of insulin detemir (Levemir®) in insufficiently controlled patients with type 1 or type 2 diabetes.
Inclusion criteria: inclusion criteria:

 Patients with insufficiently controlled type 1 or type 2 diabetes mellitus under their previous therapy
Exclusion criteria:

['Diabetes', 'Diabetes Mellitus, Type 1', 'Diabetes Mellitus, Type 2']

Diabetes
Diabetes Mellitus
Type 1
Diabetes Mellitus
Type 2


Canadian Outpatient VTE Management Registry

Summary: Primary Objective:~- To obtain prospective, clinical practice-based data on how symptomatic VTE is managed with low molecular weight heparin (LMWH) enoxaparin in Canadian outpatient settings.~Secondary Objective:~To describe the demographic and clinical characteristics of patients with symptomatic VTE including characteristics of VTE, VTE risk factors and bleeding risk factors.~To assess the frequency of patient characteristics that would necessitate adjustment in the dose or duration of enoxaparin therapy, e.g. high BMI, impaired creatinine clearance, advanced age, cancer-associated VTE.~To assess the degree of adherence in clinical practice to Consensus Guidelines (ACCP/American College of chest Physician 2008) for the management of acute VTE, vis a vis:~Appropriate dosing of enoxaparin~Recommended duration of initial LMWH therapy~Adequate overlap of LMWH with vitamin K antagonists (VKA)~Recommended duration of longterm VKA~Frequency of use of LMWH monotherapy to treat cancer-related VTE~To access safety outcomes (including bleeding and recurrent VTE)~To describe the utilization of resources due to bleeding and recurrent VTE during the treatment period.
Inclusion criteria: inclusion criteria:

 Objectively confirmed VTE

 Initiation of enoxaparin treatment within Day 0-10 after diagnosis of VTE:

 Outpatients who will be treated with enoxaparin + VKA in combination are permitted to receive initial treatment other than enoxaparin for a maximum of 48 hours or 2 treatment doses preceding entry into the study

 Outpatients on enoxaparin monotherapy are permitted to receive up to 10 days of treatment other than enoxaparin preceding entry into the study.

Exclusion criteria: :

 - Medical or psychiatric disorders associated with altered cognition or mentation that precludes understanding of the informed consent process.

 The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.


Children s Growth and Behavior Study

Summary: Background:~- Studies show that many factors affect children s eating behavior and health. These include sleep, mood, thinking skills, and genetics. Studying children over time may identify children at higher risk for eating-related health concerns.~Objective:~- To understand how genes and environment influence eating behavior and health over time.~Eligibility:~- Children ages 8 17 in good general health.~Design:~Screening visit 1: Medical history, physical exam, body measurements, and questions.~14 days: Participants will wear a wrist monitor and answer smartphone prompts about eating and mood. They may give a stool sample.~Screening visit 2:~Body measurements.~Saliva, urine, and blood samples.~Heart tests.~Meals provided (after fasting overnight).~Questionnaires and interview.~Behavior, thinking, and exercise tests.~X-ray of left wrist and full body.<TAB>~Some parents may have medical history, physical exam, and questions at screening visits. They may answer questions at the yearly visits.~Participants will have up to 6 yearly visits. They will give a urine sample and body measurements, and repeat the X-rays. They will have questions and behavior and thinking tasks. They may give stool samples. Visits will range from 3 to 8 hours.~Participants may choose to participate in other studies:~Stress and Hormones, 1 visit: While resting, participants will give saliva samples and have their heart monitored. Then they will do math. They will repeat the resting part, then do a computer task.~Brain Imaging, 2 visits: Twice, participants will perform tasks with a magnetic cone on their head then answer questions. Once, they will have an MRI, lying still in a scanner with a coil on their head.~Sleep, 2 visits: Participants will have food provided, answer questions and do tasks.~Participants will be compensated for the time and inconvenience involved with completing study procedures.~...
Inclusion criteria: inclusion criteria:

 Volunteers will qualify if they meet the following criteria.

 Age 8 17 years.

 Weight, height and BMI greater than or equal to 5th percentile for age and sex according to Centers for Disease Control and Prevention 2000 US standard.

 Cognitively capable of completing study procedures (FSIQ greater than or equal to 70).

 Good general health based on a normal history and physical examination (with the exception of overweight and minor, well-controlled illnesses).

Exclusion criteria: :

 Individuals will be excluded (and provided treatment referrals as needed) for the following reasons:

 History of major cardiovascular disease or any other serious obesity-related complication as assessed during history and physical exam. Individuals with untreated or major illnesses relating to the endocrine and/or cardiovascular systems are excluded because these illnesses will likely influence outcomes. Such obesity-related comorbidities include hypertension (defined by age- sex- and height- specific standards, and fasting hyperglycemia consistent with diabetes (fasting glucose > 126 mg/dL).

 Presence of other major illnesses: renal, hepatic, gastrointestinal, most endocrinologic (e.g., Cushing syndrome, untreated hyper- or hypothyroidism), hematological problems or pulmonary disorders (other than asthma not requiring continuous medication). Non-serious medical illnesses, such as seasonal allergies, will be reviewed on a case-by-case basis.

 Regular use of any medication known to affect body weight or eating behavior (e.g., many medications prescribed for attention deficit hyperactivity disorder, or ADHD). Medication use for non-serious conditions (e.g., acne) will be considered on a case-by-case basis.

 Current pregnancy or a history of pregnancy. A negative pregnancy test before starting the study will be required for postmenarcheal girls.

 Current and regular use of tobacco products and/or alcohol.

 A significant reduction in weight during the past three months, for any reason, exceeding 5% of body weight.

 A history of significant or recent brain injury that may considerably influence performance on neurocognitive measures (i.e., any history of loss of consciousness greater than or equal to 30 minutes associated with a head injury, any history of memory loss or hospitalization associated with a head injury, or greater than or equal to 2 concussions within last year).

 Presence of any significant, full-threshold psychiatric disorder based on DSM criteria such as schizophrenia, bipolar disorder, alcohol or substance abuse, anorexia or bulimia nervosa, or any disorder that, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study. These individuals will not be permitted to enroll in the current study and will be referred for treatment. Individuals who present with other psychiatric disorders, including sub-threshold psychiatric disorders, will be permitted to enroll in the study. Sub-threshold psychiatric disorders include symptoms that do not meet diagnostic threshold based on the DSM criteria for mental disorders, but which are nevertheless significantly impairing or distressing. If, based on the opinion of the investigators, a participant requires treatment for his/her psychiatric symptoms,, the individual will be referred for treatment. Participants who develop any psychiatric disorder or significant psychiatric symptoms at any follow-up assessment during the study will not be excluded, but will be provided with treatment referrals.

 Any other condition in the child or parents/guardians that, in the opinion of the investigators, would impede compliance or possibly hinder completion of the study (e.g., significant Learning Disorder).

 Additional exclusions for (optional) stool sample collection include:

 Stool Sample only:

 Diagnosis or history of inflammatory bowel disease, including ulcerative colitis or Crohn's disease, celiac sprue, irritable bowel syndrome, or other inflammatory disorders of the intestine.

 Diarrhea within 1 week prior to sampling.

 Antibiotic use within 4 weeks prior to sampling.

 In addition, Experiments 1 and 2 have specific additional exclusions:

 Experiment 1 only:

 Regular use of medications that could influence autonomic or endocrine functioning, including alpha and beta blockers, oral contraceptives, or prescription pain medication.

 Scoring as highly active on the International Physical Activity Questionnaire (due to decreased cortisol reactivity).

 Experiment 2 only:

 Participants will be excluded if MRI and MEG is contraindicated (metal in body, braces, glasses required to correct vision, presence of non-organic [e.g., cochlear] implants or cerebral clips, permanent tattooed makeup or general tattoos in a dangerous location on the body or made with colors whose content in iron cannot be definitely ruled out.

 Youth will be excluded if they are left-handed.

 All participants will receive a written explanation of the purposes, procedures, and potential hazards of the study. Communication of this information and of the participant s assent as well as the consent of the parent or guardian will be documented in the medical record and copies of all signed documents given to each family. All participants will be informed of their right to withdraw from the study.

['Obesity', 'Eating Behaviors', 'Healthy Volunteers']

Obesity
Eating Behaviors
Healthy Volunteers


Double-blind, Multiple Dose Study of Tezepelumab (AMG 157) in Adults With Mild Atopic Asthma

Summary: The purpose of this study is to assess the late and early asthmatic response after an allergen inhalation challenge in adults with mild atopic asthma after receiving multiple doses of tezepelumab (AMG 157), as well as the safety, tolerability, immunogenicity, and pharmacokinetics of multiple doses of tezepelumab in adults with mild atopic asthma.
Inclusion criteria: inclusion criteria:

 Male or female subjects with history of mild atopic asthma between 18 and 60 years-of-age

 Body mass index (BMI) between 18 and 35 kg/m^2

 Normal or clinically acceptable physical examination (PE), clinical laboratory values, and electrocardiogram (ECG); clinically acceptable PE includes history of mild atopic asthma

 Used only inhaled short-acting β2-agonists infrequently to treat asthma

 No current exposure to allergens to which subject experiences asthmatic responses

 No other lung disease, exacerbations of asthma or lower respiratory tract infections for at least 6 weeks prior to screening

 Positive skin prick test to common aeroallergens at screening

 Additional inclusion criteria apply

Exclusion criteria: :

 History or evidence of a clinically significant disorder (including psychiatric), condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion;

 History or current medical conditions that are contraindicated for methacholine challenge, such as myocardial infarction or stroke within previous 3 months, known cardiac disease, uncontrolled hypertension and aortic or cerebral aneurysm

 Evidence of active or suspected bacterial, viral, fungal or parasitic infections within past 6 weeks

 Subject has know type I/II diabetes

 History of residential exposure to tuberculosis or has a positive purified protein derivative (PPD) or QuantiFERON test within 4 weeks before randomization

 Subject who has history of malignancy of any type within 5 years prior to enrollment

 Subjects tested positive for drugs/alcohol or nicotine use at screening

 Subjects tested positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C

 Additional


Rapid Diagnostic Tests and Clinical/Laboratory Predictors of Tropical Diseases In Patients With Persistent Fever in Cambodia, Nepal, Democratic Republic of the Congo and Sudan (NIDIAG-Fever)

Summary: Tropical fevers have been a diagnostic challenge from the antiquity. Nowadays, despite the availability of good diagnostic capacities, undifferentiated febrile illnesses continue to be a thorny problem for travel physicians. In developing countries, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers even more complex. Health care workers must often rely on syndrome-oriented empirical approaches to treatment and might overestimate or underestimate the likelihood of certain diseases. For instance Neglected Tropical Diseases (NTD) contribute substantially to the burden of persistent (more than 1 week) fevers in the Tropics, causing considerable mortality and major disability. These diseases are however rarely diagnosed at primary health care (PHC) level. The difficulty in establishing the cause of febrile illnesses has resulted in omission or delays in treatment, irrational prescriptions with polytherapy, increasing cost and development of drug resistance.~In resource-limited settings, clinical algorithms constitute a valuable aid to health workers, as they facilitate the therapeutic decision in the absence of good laboratory capacities. There is a critical lack of appropriate diagnostic tools to guide treatment of NTDs. While clinical algorithms have been developed for some NTDs, in most cases they remain empirical. Besides, they rarely take into account local prevalence data, do not adequately represent the spectrum of patients and differential diagnosis at the primary care level and often have not been properly validated. The purpose of the study is to develop evidence-based Rapid Diagnostic Test (RDT)-supported diagnostic guidelines for patients with persistent fever (≥ 1 week) in the Democratic Republic of the Congo (DRC), Sudan, Cambodia and Nepal.
Inclusion criteria: inclusion criteria:

 fever for ≥ 1 week

 ≥ 5 years old (18 years onward in Cambodia)

Exclusion criteria: :

 unwilling or unable to give written informed consent

 unable in the study physician's opinion to comply with the study requirements

 existing laboratory confirmed diagnosis

 need of immediate intensive care due to shock or respiratory distress

['rk28 ICT', 'IT LEISH (rK39)', 'Immunochromatographic HAT test', 'HAT Serostrip', 'Card Agglutination Trypanosoma Test (CATT)-10', 'Typhidot M', 'S. typhi IgM/IgG', 'Test-it Typhoid IgM', 'Test-it Leptospirosis IgM', 'Leptospira IgG/IgM']

['Visceral Leishmaniasis', 'Human African Trypanosomiasis', 'Enteric Fever', 'Melioidosis', 'Brucellosis', 'Leptospirosis', 'Relapsing Fever', 'Rickettsial Diseases', 'HIV', 'Tuberculosis', 'Malaria', 'Amoebic Liver Abscess']

Visceral Leishmaniasis
Human African Trypanosomiasis
Enteric Fever
Melioidosis
Brucellosis
Leptospirosis
Relapsing Fever
Rickettsial Diseases
HIV
Tuberculosis
Malaria
Amoebic Liver Abscess


Prednisolone +/- Addition of Anti-CD20 Antibody, Rituximab, in Patients With Immune Hemolytic Anemia

Summary: The conventional treatment in warm-antibody dependent autoimmune haemolytic anaemia (AIHA) is high-dose glucocorticoid, but in more than half of the patients, haemolytic activity will recur after end of treatment or during the gradual reduction in dose of the drug. As a result, many patients will finally be splenectomized or be treated with long-term glucocorticoids or other immunosuppressive drugs as azathioprine or cyclophosphamide. Recent studies have shown however, that some patients will respond to treatment with the chimeric anti-CD 20 antibody Rituximab and is some cases, the response is permanent. In most of the studies, Rituximab has been used in refractory disease or at least as second line treatment. In this study, patients with AIHA are randomized to receive either high-dose prednisolone with gradual reduction in dose over 2-3 months alone or in combination with Rituximab 375 mg/m2 once a week for 4 weeks. The efficacy of Rituximab will be evaluated by a comparison of the patients in the two treatment arms. The primary treatment goal is a reduction in the number of patients who obtain long-term complete or partial remission. The secondary treatment goal is a reduction in patients who will be splenectomised or receive other immunosuppressive drugs. Finally a comparison of side effects of the treatments will take place.
Inclusion criteria: inclusion criteria:

 Age 18 years or over

 Clinical and biochemical signs of haemolytic anaemia

 Positive Coombs test with anti-IgG on its own or with anti-CD3d

 Adequate contraceptive measures (intrauterine device, contraceptive pill or gestagen deposit) for women of childbearing potential

Exclusion criteria: :

 Performance status > 2

 Previous treatment with Rituximab

 Other immune suppressive or anti neoplastic treatment including prednisolone within 3 months

 Auto immune haemolytic anaemia within 6 months

 Other serious disease

 Pregnant women and nursing mothers. Adequate contraceptive measures must be taken for the duration of the study.

 Contraindication for treatment with Rituximab, i.e. patients that develop hypersensitivity/allergy to the contents of the drug or have antibodies against murine proteins.

 Active infection which requires antibiotic treatment

['prednisolone + mabthera', 'Prednisolone']


Dexamethasone and Wound Healing After Thyroid Surgery

Summary: Dexamethasone is a potent glucocorticoid with analgesic and anti-emetic effects [1-3]. Perioperative single-dose dexamethasone therapy has been used for several purposes: to reduce post-operative nausea and vomiting (PONV), pain and sore throat. There are also some reports on beneficial effects of less cardiac arrhythmia, improved appetite and less edema from glucocorticoids. Preoperative small dose of dexamethasone was reported to prevent reversal laryngeal nerve injury and improve voice quality after thyroid surgery. While accepted wildly in clinical anesthesia practice, the immune-press related potential risks of side effects associated with dexamethasone, such as delayed wound healing, infection, as well as effects on blood sugar, make the use of perioperative single dose of glucocorticoid controversial. The effect of perioperative dexamethasone on wound healing varied with different types of surgery. The present study will observe the effect of dexamethasone on the safety of thyroid surgery.
Inclusion criteria: inclusion criteria:

 Elective total thyroidectomy or hemithyroidectomy with lymphadenectomy for thyroid cancer

Exclusion criteria: :

 Age > 65 years, < 18 years

 Thyroid tumor with Grave's disease

 Thyroid tumor size over 5 cm

 Second or more than 2 times for thyroid surgery

 Non-traditional pathway for thyroid surgery

 ASA > II

 Pharyngitis

 Smoking, alcohol drinking history

 Contraindication or long term use of dexamethasone (allege, ulcer bleeding history, et al)


Induction of Mild Hypothermia in Resuscitated Cardiac Arrest Patients

Summary: The primary objectives of this study are to determine the safety and feasibility of inducing mild hypothermia using a non-invasive thermoregulatory device, the Medivance Arctic Sun Temperature Management System, in patients resuscitated after cardiac arrest.
Inclusion criteria: inclusion criteria:

 Male or female patients ≥ 18 years.

 Witnessed out-of-hospital cardiac arrest of presumed cardiac origin in which the initial rhythm is ventricular fibrillation, ventricular tachycardia, pulseless electrical activity (PEA) or asystole.

 First attempt at resuscitation (ACLS or CPR) by emergency medical personnel initiated within 15 minutes of collapse.

 Restoration of spontaneous circulation (ROSC) within 60 minutes of collapse.

 Time from restoration of spontaneous circulation to initiation of cooling is ≤ 6 hours.

 Informed consent provided by authorized representative/family member.

Exclusion criteria: :

 Temperature of less than 35C on admission.

 Comatose or vegetative state prior to cardiac arrest.

 Positive pregnancy test.

 Purposeful response to verbal commands after ROSC and prior to initiation of hypothermia.

 Evidence of hypotension (MAP<60) for more than 30 minutes after ROSC and prior to initiation of hypothermia.

 Evidence of hypoxia (oxygen saturation<85% despite supplemental oxygen) for more than 15 minutes after ROSC and prior to initiation of hypothermia.

 Terminal illness that preceded the arrest (life expenctancy < 1 year).

 Patients experiencing cardiogenic shock.

 Patients continuing to experience refractory ventricular arrhythmias at the time of enrollment.

 Patients receiving 2 or more high dose vasopressors.

 Active bleeding or known preexisting coagulapathy.

 Patient history of cold agglutinin disease.

 Patient history of Raynaud's Disease.

 Patient history of Sickle Cell disease.

 Evidence of compromised skin integrity or irregularities (such as urticaria, rash, lacerations, burns, abrasions.

 Patient weight > 114 kg (250 lbs) or < 50 kg (110 lbs)

 Enrollment in another therapeutic study.


A Pilot Study of Early Postpartum Intrauterine Contraception

Summary: This is a prospective clinical trial of ultrasound guided intrauterine contraception insertion 10 minutes - 48 hours after vaginal delivery of single infant. A six month follow-up will entail three follow-up visits; 4-6 weeks, 3 months, and 6 months.~The objective of this study is to measure intrauterine device (IUD) expulsion and the feasibility of conducting a future clinical trial to evaluate placement of the levonorgestrel-releasing intrauterine contraceptive 10 minutes - 48 hours postpartum.
Inclusion criteria: inclusion criteria:

 Currently pregnant with a single gestation of at least 27 completed weeks estimated gestational age, with no complications of pregnancy including, but not limited to, preeclampsia, non-gestational diabetes, anemia.

 Desires to use intrauterine contraception (IUD) after delivery

 Anticipates having a vaginal delivery

 No intention to leave the area 7 months after enrollment

 Able to consent to participate in the study in English

 Has no known uterine anomalies

 Has no allergies to any components of the intrauterine contraception

Exclusion criteria: :

 Prior cesarean delivery

 Having been treated for pelvic inflammatory disease within 3 months prior to the start of the pregnancy

 Allergic to betadine

 Allergy to lidocaine

 Medical or personal conditions which in the judgment of study staff contradict participation in the study

 Any contraindications to use of the levonorgestrel-releasing intrauterine contraceptive system which includes: known or suspected breast carcinoma, acute liver disease or liver tumor, history of ectopic pregnancy, cervical cancer or carcinoma in situ

 After enrollment, and after delivery of the infant but before IUD insertion subjects will be excluded by checking with the attending obstetric physician and/or obstetric medical chart for the following:

 Endometritis or chorioamnionitis during the intrapartum period

 Membranes ruptured for greater than 24 hours prior to delivery

 Fever greater than or equal to 38C

 The need to use additional medications other than pitocin and/or misoprostol to control postpartum bleeding

['Levonorgestrel-Releasing Intrauterine Contraceptive System (LNG-IUS), 52 Mg, 5 Year Duration']


Fast MR for Young Children With Traumatic Brain Injury

Summary: This proposal will test the diagnostic utility of fast magnetic resonance (MR) in young children with Traumatic brain Injury (TBI).~In children, TBI causes >2000 deaths, 35,000 hospitalizations and 470,000 emergency department visits in the US each year, making it a leading cause of pediatric disability and death. Currently 20-50% of these children undergo computed tomography (CT) scanning, exposing them to harmful radiation, and increasing their lifetime risk of cancer. Risks are especially increased in children because the neurologic exam is less reliable, because growing tissues are more vulnerable to radiation, and because children have more years to accumulate harmful mutations.~Fast MR is a short, motion-tolerant protocol that has been used in children with shunted hydrocephalus to eliminate radiation exposure without the need for sedation. However, fast MR has not been validated in children with TBI, a critical gap. The investigators will measure feasibility and diagnostic utility of fast MR in children < 6 years (72 months) old who undergo head CT for TBI.~The Investigator will recruit children in whom a head CT is ordered for TBI. Consenting subjects will undergo fast MR shortly after CT and results will be compared to determine: 1) whether fast MR identifies all traumatic injuries identified by CT and 2) whether fast MR without sedation can be performed quickly and successfully.
Inclusion criteria: inclusion criteria:

 Children <72 months old in whom a head CT is ordered/obtained with concerns for TBI

 Present to the Children's Hospital Colorado (CHCO) Emergency Department (ED) or inpatient wards

Exclusion criteria: :

 Contraindication to MR (e.g. pacemaker, implanted metallic object incompatible with MR)

 Prior diagnosis of TBI, structural brain lesion or prior brain surgery including shunted hydrocephalus

 Prior participation in this study

 Clinically unstable in the opinion of the patient's attending physician

 Wards of the State

 TBI not included in the differential diagnosis of the patient's attending physician (e.g. the indication for imaging is concern for infections, tumor, autoimmune or inflammatory disease) or if imaging has already identified a non-traumatic source for symptoms


To Scan or Not to Scan: The Role of Follow-up CT Scanning for Management of Chronic Subdural Hematoma After Neurosurgical Evacuation

Summary: Chronic subdural hematoma (CSH) is one of the most common bleedings of the head. These hematomas develop after minor head trauma and increase in size over weeks. Patients usually present with headaches, gait disturbances, language problems or confusion. The state of the art treatment of a symptomatic chronic subdural hematoma is to remove the hematoma by burr hole trepanation.~The optimal follow-up for operated patients remains controversial. Due to the known high rate of a second hematoma at the same place (usually within weeks), one strategy is to perform serial computer tomography scans in order to identify recurrent hematomas early. The radiologic evidence of a second hematoma often leads to reoperation, even if the patient has no, or just slight symptoms. Another strategy after surgical hematoma evacuation is to closely follow the patient with neurological examinations and perform neuroimaging only in case of new symptoms. Advocators of this strategy argue that a follow-up with routine CT scans may be harmful due to additional and maybe unnecessary surgeries and hospital days in a patient population marked by advanced age and fragility.~The aim of the current study is to evaluate the role of computer tomography scanning in the postoperative follow-up after removal of a chronic subdural hematoma. Participants of this study will be allocated by chance to one of two study groups: Patients allocated to group A will receive a computer tomography scan on day 2 and again on day 30 after surgery in addition to a clinical examination. Patients allocated to group B will be examined clinically on day 2 and day 30 without computer tomography. All patients will undergo a final clinical examination after 6 months. The study will recruit 400 patients.
Inclusion criteria: inclusion criteria:

 Newly diagnosed chronic subdural hematoma by CT scan or MRI, operated within the last 48 hours

 Age 18 years or older

 Written informed consent from the patient to participate in the study

Exclusion criteria:

 Moribund state of health prohibiting surgery

 Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)

 Recurrent hematoma if the first surgery was performed before study start

 CSH due to spontaneous spinal CSF fistula or meningeosis carcinomatosa

 Pregnancy

 Patient with Metastatic Disease and a high possibility to pass away in the next 6 month