Datasets:

pat-jj

/

ClinicalTrialSummary

like 0

Background:~Cardiac surgery is associated with pain in the post-operative period. Recently the ability to infuse local anesthetic drugs into the area of the sternal wound has become available. The studies that have been done thus far have shown efficacy in controlling pain but have been too small to show clinically significant patient outcome differences.~Specific Aim:~We plan to conduct a phase II/III study of local anesthetic infusion into the sternal wound in adult patients undergoing cardiac surgery.~In the Phase II study, 40 patients will be enrolled in a prospective observational open label, dose escalation study of safety and efficacy of local anesthetic infusion into the sternal wound. Outcome measures for efficacy will be visual analog pain (VAP) scores and opioid consumption. Outcome measures for safety will be plasma ropivacaine concentrations and adverse events.~The dose determined in the phase II study will be used in the Phase III study. In this study, 200 patients will be enrolled in a double blind prospective, randomized, double blind; placebo controlled trial of local anesthetic infusion into the sternal wound. Outcome measures for efficacy will be visual analog pain (VAP) scores, opioid consumption, time to extubation, pulmonary function tests, duration of ICU and hospital stay, all cause morbidity and mortality. Outcome measure for safety will be adverse events.~Hypothesis:~Local anesthetic infusion into the sternal wound will be safe and result in improved pain control and reduced time to extubation, duration of ICU and hospital stay.~Significance:~This will be the first large randomized controlled clinical trial assessing outcomes with the use of local anesthetic infusion into the sternal wound in patients undergoing open-heart surgery.

Cardiac surgery is associated with pain in the post-operative period. We plan to conduct a study of local anesthetic, ropivacaine, infusion into the sternal wound in adult patients undergoing cardiac surgery to see if it will be safe and result in improved pain control and reduced time to extubation, duration of ICU and hospital stay.

Tranexamic acid is administered intravenously to prevent bleeding associated with cardiac surgery and cardiopulmonary bypass. The current dosing regimen for tranexamic acid was empirically derived based upon pharmacokinetics in normal patients receiving the drug. We have developed an assay for tranexamic acid and found that the plasma concentration of tranexamic acid varies greatly between patients and also over time within each patient, especially in patients with renal insufficiency. We have developed an alternative dosing schedule for tranexamic acid that incorporates the effects of renal function on tranexamic acid concentrations. The objective of this preliminary study is to determine if this new dosing schedule can achieve the desired plasma concentration of tranexamic acid and reduce intra and inter patient variability in tranexamic acid plasma concentrations relative to the current dosing schedule. The results of this study will be used in a larger subsequent study of what level of plasma tranexamic acid concentration is needed to prevent bleeding and transfusion of blood products in patients undergoing cardiac surgery.

Tranexamic acid is administered intravenously to prevent bleeding associated with cardiac surgery and cardiopulmonary bypass. We have developed an assay for tranexamic acid. We have developed an alternative dosing schedule for tranexamic acid. The objective of this preliminary study is to determine if this new dosing schedule can achieve the desired plasma concentration of tranexamic acid and reduce intra and inter patient variability in tranexamic acid plasma concentrations relative to the current dosing schedule.

The growing success of interventions and requirement for day case or outpatient procedures has led to a concomitant rise in the use of arteriotomy closure devices (ACD) to achieve hemostasis and allow early mobilization following arterial punctures. ACD have emerged as an alternative to traditional mechanical compression after percutaneous coronary intervention (PCI). When compared to manual compression, several studies have confirmed patient comfort, reduced time to achieve hemostasis, reduced time to ambulation, and early discharge.~Recently, CLIP Trial was conducted to evaluated the safety and efficacy of the StarClose device in subjects undergoing diagnostic and interventional catheterization procedures. A total of 17 U.S. sites enrolled 596 subjects, with 483 subjects randomized at a 2:1 ratio to receive StarClose or standard compression of the arteriotomy after the percutaneous procedure. The study included roll-in (n=113), diagnostic (n=208), and interventional (n=275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. This trial demonstrated that the StarClose Vascular Closure System is noninferior to manual compression with respect to the primary safety endpoint of major vascular events in subjects who undergo percutaneous interventional procedures. StarClose significantly reduced time to hemostasis, ambulation, and dischargeability when compared with compression.~However, there are no studies randomly comparing these two closure devices. Therefore, this study was designed to evaluate the efficacy and safety of Starclose (Abbott Vascular Devices) for femoral access site closure in patients undergoing PCI compared to Angio-Seal STS Plus (St. Jude Medical).

This study was designed to evaluate the efficacy and safety of Starclose (Abbott Vascular Devices) for femoral access site closure in patients undergoing PCI compared to Angio-Seal STS Plus (St. Jude Medical).

Healthy volunteers will be enrolled in a dietary sodium intervention to examine impact on vascular function.

The purpose of this study is to look at the effects of high- and low-salt diets on blood vessel function in healthy subjects.

Introduction & background In emergency surgery, although surgical and resuscitation techniques were improved, the postoperative complications and mortality rates are still high and however higher than for those patients that underwent to elective surgery (1-3). Using a Metallic prosthesis stent in an obstructed colon allows to transform an emergency surgical case into an elective surgery case. This allows to restore the bowel transit and to operate in elective condition reducing morbidity, mortality and the need of an enterostomy (4-10).~Although there are recent outcomes on literature about use of a decompressive stent before surgery in obstructed patients from malignant colic tumours, there are no prospective and randomised studies were stent positioning followed by elective surgery is compared with emergency surgery.~Study design Prospective, randomized multicentric clinical trial where samples are patients with emergency room diagnosis of obstructing colonic neoplasm.~Once informed and obtained consent, patients will be included in the study and randomized in one of the two branches of the study: A.- enteral stent positioning followed by second time resection in the same hospital stay. B.- emergency surgical treatment consisting in Hartmann operation or resection with same time anastomosis. Results from transit reconstruction in patients underwent Hartmann operation will be considered in the study.~Short term clinical evolution control in order to determine postoperative morbility and mortality, hospital stay.~Follow-up will be performed to evaluate survival rate and disease free survival.~Endpoints To evaluate and compare the results obtained using enteral stent followed by elective surgery versus common emergency surgical techniques.~Primary endpoint will be 60 days postoperative morbidity. Others endpoints will be: postoperative mortality, length of hospital stay, need for analgesia. Long term follow up with specific instrumental controls (CT scan, US, colonoscopy or RX clysma) to identify disease recurrences or metastases as cost analysis and patient's quality of life will also be evaluated.~Statistics & randomization In prospective series analysed in different centres, the incidence of postoperative complications in patients underwent to emergency colonic surgery was 35%. The positioning of the stent associated to second time surgical elective treatment is characterized by 15% of morbidity (stent: 5%, surgery: 10%). The number of patients needed to carry on the study making statistically significant this difference (35% vs 15%) with an error alpha = 0.05 and beta = 0.2 and estimating a loss of 5% of the samples, is 72 patients in each group.~Randomization will be stratified for local extension of tumour (T4 vs others) and for presence or not of liver metastases.~Main selection criteria Inclusion of patients with malignant colonic obstruction localized between promontorium and splenic flexure and diagnosed by CTScan. Those patients with peritonitis, pneumoperitoneum, synchronic colonic tumour, pregnant or haemodynamic instability will be excluded.~Follow-up Same follow-up as patients diagnosed and treated for Colon Cancer following the protocol of each center, never less than 3 years. During follow-up required complementary studies will be performed in each case in order to evaluate local recurrence or distant metastases. Also quality of life and costs will be evaluated.~Expected results: reduction of postoperative complications and hospital stay in patients submitted to stent positioning without worsening of evolution of the neoplastic illness.

The purpose of this study is to verify whether stent positioning for malignant obstruction of the colon and rectum followed by elective surgery allows reduction of postoperative complications and hospital stay without worsening of evolution of the neoplastic illness, compared to emergency surgery.~Primary endpoint will be 60 days postoperative morbidity. Others endpoints will be postoperative mortality, length of hospital stay, need for analgesia.

The purpose of this study is to take a population of lung transplant recipients who meet UCLA criteria for induction chemotherapy with thymoglobulin and prospectively study weather giving the first dose intraoperatively versus postoperatively makes a difference with how patients do during and after lung transplantation. In addition, these cohorts will be compared to patients who do not qualify for thymoglobulin and receive either an alternative agent or no agent. The primary endpoint is primary graft dysfunction. We will also evaluate several other early and late end points such as ventilator days, ICU/hospital days, acute/chronic rejection, infection, CT chest abnormalities, and survival.~We will also collect donor lung tissue and lavage fluid for measurement of various proteins and receptor expression at two time points: (1) prior to implementation and dosing of induction chemotherapy and (2) after transplantation (following a course of induction chemotherapy). This will allow us to possibly make a connection between the profiles of the various proteins and receptors and the clinical outcomes, depending on weather the patient has received induction chemotherapy, starting intraoperatively or postoperatively.

The purpose of this study is to take a population of lung transplant recipients who meet UCLA criteria for induction chemotherapy with thymoglobulin and prospectively study weather giving the first dose intraoperatively versus postoperatively makes a difference with how patients do during and after lung transplantation.

Phosphoglycerate kinase (PGK) deficiency is a rare x-linked disorder characterized by hemolytic anemia, seizures, muscle fatigue, and progressive neurological dysfunction. The disease is caused by the deficiency of PGK, an enzyme required for ATP formation through the glycolytic pathway. PGK is an enzyme that is ubiquitous to all cells of the human body, but red blood cells, muscles, and nerve cells are most severely affected by the absence of PGK due to their reliance upon the glycolytic pathway. Mutations of the PGK gene are highly variable and result in diverse phenotypes, ranging from mild hemolytic anemia only1 to severe mental retardation and early death in childhood.2-5 The more severe phenotypes show progressive neurologic deterioration between infancy and adolescence.2,3,5 PGK-Amiens refers to a particular mutation that is an A to T transversion, which predicts an amino acid change of aspartate (Asp: GAT) to valine (Val: GTT) at the 164th position from the NH2-terminal methionine residue. This D164V mutation has been identified previously as PGK-Amiens or PGK-New York in a French and in a Chinese family respectively.3,6 This particular mutation results in the most severe phenotype. All 6 of the boys described in the literature with this mutation have had progressive neurologic decline, seizures, episodes of hemiplegia, aphasia, emotional lability, and severe hemolytic crises. Two of the boys died in childhood, 2 are institutionalized with no ability to communicate or provide self-care, and 2 are moderately mentally retarded with seizures and hemolytic anemia. The two brothers cared for at this institution have the Amiens variant of PGK deficiency.~Allogeneic bone marrow transplantation (BMT) became feasible in the 1960s after elucidation of the Human Leukocyte Antigen (HLA) complex. Since then, the therapy has evolved into an effective therapy for many hematologic disorders(7). Otherwise incurable malignancies are frequently cured by this approach, with the likelihood of cure ranging from 10% to 85%, depending on the disease and disease-status. The treatment strategy incorporates very large doses of chemotherapy and often radiation to eliminate malignant cells and to immunosuppress the recipient enough to allow engraftment of donor cells. Donor cells give rise to hematopoiesis within two to three weeks, rescuing the patient from the effects of high dose therapy. In the ideal circumstance, immune recovery and recipient-specific tolerance occurs over the following 6-18 months, and the patient is cured of his or her underlying hematologic disorder, off of immunosuppression, with a functionally intact donor-derived immune system. However, complications of the process are common and include potentially permanent or fatal organ damage from the effects of high dose chemotherapy, infection, hemorrhage, and, in particular, graft-versus-host-disease. A realistic estimate of transplant-related mortality, including deaths due to acute and chronic graft-versus-host diseases, in the standard HLA-matched sibling setting is as high as 25%. The risk of treatment related mortality thus limits the success of the approach even in younger patients and certainly precludes its use in older patients. Thus, particularly for older patients, new strategies in transplantation are needed.~Stem cells for allogeneic transplant are traditionally obtained from one of three sources: bone marrow (1), peripheral blood stem cells mobilized by provision of the growth factor GCSF (2), or umbilical cord blood (3). Each source has specific advantages and disadvantages. The desired source of stem cells for allogeneic transplant is a matched sibling donor. However, if that is not feasible, a matched unrelated donor can be sought through the National Marrow Donor Program (NMDP). The National Marrow Donor Program (NMDP) in Minneapolis, Minnesota, was established in 1986 to facilitate the search for, and procurement of, HLA-matched marrow from volunteer, unrelated marrow donors for patients with life-threatening diseases curable by SCT (7). The NMDP network consists of 99 donor centers, 108 collection centers, 150 transplant centers and a Coordinating Center in Minneapolis. As of June 29, 2003, the NMDP had a registry of 5,032,382 volunteer marrow donors and 28,574 cord blood units stored, and had facilitated 13,213 unrelated marrow transplants (marrow, PBSC and cord blood) worldwide. Over 600,000 donors in the NMDP Registry are contributed by European registries, which are affiliated with the NMDP. In addition, approximately 1 million donors are available by searching NMDP International Cooperative Registries in Europe, South America, and Asia. On average, searching patients have a 75% chance of finding a match within the NMDP, with a median time from search to transplant of less than 6 months. Vanderbilt University Medical Center is a NMDP approved aphaeresis center, collection center and transplant center and adheres to the policies and procedures of the NMDP as outlined in The 18th Edition of the NMDP Standards (effective since September 13th, 2002, implemented February 10th, 2003).~Stem cell transplantation (SCT) has been performed in children with various metabolic diseases, including mucopolysaccharide disorders (MPS), leukodystrophies, and glycoprotein metabolic disorders.8 The prototypical metabolic disorder for SCT is Hurler syndrome, or MPS IH. Hurler syndrome results from the lack of a lysosomal enzyme needed to degrade glycosaminoglycans, which then build up and cause progressive intellectual decline, hepatosplenomegaly, cardiac valvular disease, airway abnormalities, and skeletal abnormalities. SCT performed early in the disease process leads to enzyme replacement and stops progression of disease.9 SCT has helped other MPS disorders including severe Maroteaux-Lamy syndrome and Sly syndrome, but unfortunately, and for reasons not well understood, SCT has not helped in several other MPS disorders, such as Hunter, Sanfilippo, and Morquio syndromes.8 X-linked adrenoleukodystrophy is a disease that affects boys with variable degrees of severity. When boys show early MRI changes and undergo SCT, outcome is very good, with preservation of neurological and neurocognitive function.10,11 Other leukodystrophies that respond to early SCT include Krabbe disease and metachromatic leukodystrophy.8,12 Glycoprotein metabolic disorders are exceedingly rare and thus there is limited experience with SCT in patients with these disorders. There have been successful outcomes in preservation of cognitive function in α-mannosidosis,13 fucosidosis,14 Batten disease,15 and Gaucher disease Type I.16 SCT has not been able to salvage children with Fabry disease, Tay Sachs disease, Pompe disease, and Sandhoff disease.8 Again, it is poorly understood why SCT is able to stop neurologic decline in some metabolic disorders and not others.~Definitive therapy for PGK deficiency necessarily involves production of the PGK enzyme. The hemolytic anemia that is part of this disease could be cured by allogeneic stem cell transplant, as replacing the hematopoietic system would ensure production of the enzyme in the red blood cells. However, the neurologic complications of the disease would require that the enzyme can find its way into the neurons themselves. Because of the rarity of PGK deficiency, there has been as yet no controlled study to define the most efficacious approach. In fact, there is no mention of any therapy in the literature. There is currently no enzyme replacement therapy and no major research effort underway to do so. To our knowledge, stem cell transplant in this disease has not been performed except for in one 7 month old child with PGK-Amiens in Australia, who is currently being prepared for SCT. The stem cell source will be determined by the donor availability. The donor registry allows the donor the option of donating either peripheral blood or bone marrow.~(Please note all reference numbers refer to the Reference list of the study protocol, pages 9 and 10.)

Phosphoglycerate kinase (PGK) deficiency is a rare x-linked disorder characterized by hemolytic anemia, seizures, muscle fatigue, and progressive neurological dysfunction. The disease is caused by the deficiency of PGK, an enzyme required for ATP formation through the glycolytic pathway. PGK is an enzyme that is ubiquitous to all cells of the human body, but red blood cells, muscles, and nerve cells are most severely affected by the absence of PGK due to their reliance upon the glycolytic pathway. Mutations of the PGK gene are highly variable and result in diverse phenotypes, ranging from mild hemolytic anemia only to severe mental retardation and early death in childhood. The more severe phenotypes show progressive neurologic deterioration between infancy and adolescence.~This is a 2 patient study aimed at studying the role of stem cell transplant in PGK deficiency. Because the disease is so rare, the study will be limited to the 2 sibling patients followed by our group, though it would be open to other participants who would meet inclusion/exclusion criteria if such presented to us. The objective of this study is to evaluate the feasibility and efficacy of stem cell transplants to treat patients with PGK deficiency, Amiens subtype.

Modafinil produces a unique spectrum of pharmacological effects including enhanced vigilance, arousal, and wakefulness in human subjects (Bastuji and Jouvet 1988). The drug is widely used to treat narcolepsy (Banerjee, Vitiello et al. 2004), but is also effective in Attention Deficit Hyperactivity Disorder (ADHD) (Biederman, Swanson et al. 2005). Notwithstanding the expanding clinical indications for modafinil, the neurochemical mechanisms that produce therapeutic improvement remain unresolved. Pre-clinically, modafinil is a weak inhibitor of the DAT, and displays no affinity for dopamine receptor subtypes (Mignot, Nishino et al. 1994). Further evidence supporting low dopaminergic activity is the low abuse potential of modafinil (Jasinski 2000). Various theories have been proposed as alternative modes of action including enhancement of glutamate release and inhibition of Gamma-aminobutyric acid (GABA) release in various brain regions (Ferraro, Antonelli et al. 1997; Ferraro, Antonelli et al. 1997; Ferraro, Antonelli et al. 1999). However, the exact mechanisms of action of modafinil and the principle active metabolite, armodafinil, are unknown. Understanding these mechanisms of action is important in assessing the potential therapeutic role of armodafinil. We will test to see if there are differences in the degree of DAT occupancy and D2 binding of armodafinil compared with that of traditional stimulants.~The main target of typical stimulants in the brain is the dopamine transporter (DAT) (Volkow, Wang et al. 1998). We have an exquisitely sensitive methodology to measure DAT occupancy using C-11 altropane and Positron Emission Tomography (PET) (Fischman, Bonab et al. 2001). Our group has previously documented the central nervous system pharmacokinetics of several psychiatric drugs (including methylphenidate) using similar techniques. (Christian, Livni et al. 1996; Fischman, Bonab et al. 1996; Fischman, Alpert et al. 1997; Salazar and Fischman 1999; Fischman, Alpert et al. 2002; Spencer, Biederman et al. 2006).~Increases in intrasynaptic (extracellular) dopamine concentrations associated with medications are routinely measured by changes in C-11 raclopride binding in PET scans. C-11 raclopride binds to postsynaptic D-2 receptors. If the intrasynaptic concentration of dopamine increases, it competes with raclopride leading to a weaker signal (i.e. decreased raclopride binding to D-2 receptors). After administration of a stimulant, associated increases in intrasynaptic dopamine compete with C-11 raclopride binding in this manner (Volkow, Wang et al. 2002). By using this technology we can document the change in D-2 binding in the intrasynaptic space achieved by armodafinil, and compare it to that achieved by a typical stimulant.~To this end, using two PET ligands (C-11 altropane and C-11 raclopride), this protocol seeks to compare the DAT receptor occupancy and the increased intrasynaptic dopamine produced by armodafinil to previous studies of methylphenidate. This research will provide novel and unique information toward better understanding the mechanisms of action of armodafinil in comparison to those of typical stimulants.

The specific aims of this study are 1) to document the Dopamine Transporter (DAT) receptor occupancy of armodafinil using positron emission tomography (PET) scanning with C-11 altropane as the ligand and 2) to document the increased intrasynaptic dopamine produced by armodafinil using PET scanning with C-11 raclopride as the ligand. We hypothesize that DAT occupancy will be low with armodafinil; less than the DAT occupancy produced by therapeutic doses of methylphenidate. We also hypothesize that increases in intrasynaptic dopamine will be relatively low with armodafinil.

The purpose of the study will be to demonstrate whether Mohs micrographic surgery can be performed with a lower total dose of local anesthesia (and greater patient safety) when using 0.5% lidocaine with 1:200,000 epinephrine versus 1% lidocaine with 1:100,000 epinephrine. Mohs micrographic surgery is a multi-staged, same-day procedure used to remove skin cancers under local anesthesia. Reconstruction of the surgical wound is also performed under local anesthesia, usually immediately after achieving tumor clearance.~This randomized, double-blind study will systematically compare the total dose of 1.0% lidocaine with 1:100,000 epinephrine versus 0.5% of lidocaine with 1:200,000 epinephrine needed to achieve local anesthesia during Mohs micrographic surgery (MMS). All healthy adult volunteers (18 years or older) undergoing Mohs micrographic surgery at the Hospital of the University of Pennsylvania's Department of Dermatology and Dermatologic Surgery between June 1, 2007 and August 31, 2007 will be eligible to participate in the study. Our primary intervention will be to record the total dose of lidocaine administered throughout all of the MMS stages and reconstructions using either of the two lidocaine concentrations. A secondary intervention will be to record each patient's level of pain control in order to demonstrate that patient comfort is effectively achieved with a lower total dose of local anesthesia. Pregnant or breast-feeding subjects, those with a history of allergic or other adverse reaction to lidocaine or epinephrine, and those who are cognitively impaired will be excluded. In addition, if the surgeon believes that a patient has a tumor which, due to size or anatomic site, may put him at risk for requiring a dose of lidocaine that approaches the threshold of toxicity, this patient will be excluded from the study.

The purpose of the study will be to demonstrate whether Mohs micrographic surgery can be performed with a lower total dose of local anesthesia (and greater patient safety) when using 0.5% lidocaine with 1:200,000 epinephrine versus 1% lidocaine with 1:100,000 epinephrine.

Child maltreatment is the general term used to characterize all forms of child abuse, including neglect and physical, sexual, and emotional abuse. These forms of maltreatment can lead to a large number of child developmental, emotional, and behavioral difficulties. As adults, children who are maltreated are more prone to unhealthy behaviors and conditions, such as drug and alcohol abuse, smoking, eating disorders, and depression. A previous study found that Project SafeCare, a treatment program that provides parent training to families with children who were at risk for or victims of maltreatment, resulted in fewer child welfare reports. Participants in Project SafeCare reported improvements in child healthcare, home safety, and parent-child relations. However, the study suggested that the SafeCare program may not be equally effective in decreasing the occurrence of all forms of child maltreatment, particularly child physical abuse. This study will determine the effectiveness of a complex evidence-based practice program, extending upon the SafeCare program, in reducing the occurrence of physical abuse and other forms of child maltreatment.~Participants in this study will receive services from Oklahoma Comprehensive Home-Based Services (CHBS), a program provided to families with issues of child abuse and neglect. Upon entry into the CHBS program, participants will undergo a computerized interview, lasting between 1 and 2 hours. The interview will include questions about family strengths and weaknesses, personal beliefs, substance abuse history, and opinion on CHBS. This computerized interview will be repeated at the end of treatment, approximately 6 to 12 months later. During the first few weeks of CHBS, an agent will make five visits to the homes of participants to observe pretreatment family life. Treatment services will concentrate on improving healthcare skills, parent-child interactions, and safety in homes and will specifically address ways to reduce physical abuse and other identified family issues. Study participation will continue for 12 months after completion of CHBS. Study researchers will obtain child welfare reports from the Department of Human Services (DHS) for up to 10 years after completion of CHBS.

This study will determine the effectiveness of a complex parent training program, based on the SafeCare model, in reducing the occurrence of child maltreatment.

Current assessment of organ tissue viability by surgeons in the operating room is limited to crude estimates such as overt physical examination, measurement of laboratory values and physical measurements of vascular flow and resistance. The ability to non-invasively measure tissue perfusion and oxygenation would provide the surgeon an improved means to assess if an injured organ will survive. The recent development of real time infrared (IR) and Near Infrared Imaging Spectroscopy (NIRIS) digital cameras has allowed for the determination of tissue perfusion and oxygenation in a non-invasive fashion. Although in the early stages of development, the application of infrared and NIRS technology holds great promise to permit the surgeon to better assess the viability of tissues in ways that have not been possible. We propose to evaluate infrared and NIRS technology in the assessment of kidney allografts using data previously collected during recipient operations at the NIH.

Current assessment of organ tissue viability by surgeons in the operating room is limited to crude estimates such as overt physical examination, measurement of laboratory values and physical measurements of vascular flow and resistance. The ability to non-invasively measure tissue perfusion and oxygenation would provide the surgeon an improved means to assess if an injured organ will survive. The recent development of real time infrared (IR) and Near Infrared Imaging Spectroscopy (NIRIS) digital cameras has allowed for the determination of tissue perfusion and oxygenation in a non-invasive fashion. Although in the early stages of development, the application of infrared and NIRS technology holds great promise to permit the surgeon to better assess the viability of tissues in ways that have not been possible. We propose to evaluate infrared and NIRS technology in the assessment of kidney allografts using data previously collected during recipient operations at the NIH.

Project Proposal~Sterimar vs Saline Sprays in nasal surgical aftercare - a blinded, randomised trial.~Gundula Thiel, Andy Evans, Kim Ah-See~Background~Patients undergoing nasal surgery commonly experience a variety of symptoms in the post-operative period including blockage, running, pain, bleeding and reduction in sense of smell. A variety of preparations are currently recommended for symptomatic relief in the post operative period. These include saline irrigations and sniffs, steam inhalations, decongestants and steroid drops. These are intended to reduce swelling and crusting and their resultant symptoms.~There is currently no level 1 evidence in literature to support the use of any particular preparation over others in nasal surgical aftercare.~A recent randomised controlled trial carried out in this department, comparing use of xylometazoline based decongestants vs Sterimar seawater nasal spray, showed a lower pain scoring in the Sterimar group but no other significant differences. This study is as yet unpublished.~Sterimar spray is a spray made from seawater which is diluted to make the solution isotonic.~Traditionally, other forms of Saline sniffs and rinses are also used for the above mentioned applications.~It is easy to make up an isotonic saline solution, using 5 grams of salt (1 teaspoon) for every ½ litre of boiled water. This can then, after cooling off, be applied to the nasal cavities with the help of a standard 10 ml syringe which is provided to the patient at discharge.~As Sterimar is not yet on the hospital formulary, the cost for the treatment is currently borne by the patient. For the duration of the study, patients randomized into the Sterimar group will be provided with the medication free of charge.~We consider it unlikely that patients randomised into the saline spray group will supplement this treatment by buying further saline sprays from the chemist at their own expense.~To establish this and to follow up patients after the trial period, we will establish a research clinic. Patients will be reviewed in a clinic dedicated to patients taking part in this trial approximately 2 weeks after surgery, after completion of the trial period.~The trial will help to establish efficacy and symptom control and advantages of one solution and delivery device over the other.~If home-made saline sprays could be used to similar effect as Sterimar, the cost for this form of surgical aftercare could be lowered significantly, both for the patient and the NHS.~We propose to conduct a single blinded, randomised trial comparing saline sprays vs Sterimar, a commercially available aerosolised isotone saline solution, comparing patients' symptom scores following septal surgery.~The MHRA confirmed that neither the Sterimar nor the home made saline spray are considered Investigational Medicinal Products.~Methodology~Setting~ENT unit, Aberdeen Royal Infirmary, teaching hospital~Inclusions / exclusions~Patients undergoing septoplasty and septoplasty in conjunction with turbinate surgery will be recruited. Those undergoing additional procedures including polypectomy will be excluded, as will all patients whose post-operative recommendations are for steroids or other take home medications that may bias results.~Recruitment~Patients fitting the inclusion criteria will be approached in the Outpatients clinic. The decision for septoplasty +/- turbinate surgery will be made there and consent for the operation will be taken. A patient information sheet will be administered by the lead investigator or other medical staff on the same day, allowing the patient ample time to discuss the matter with relatives and medical staff. Patients will be left to read the information sheet and then re-approached to assess willingness to be included in the trial. The procedure of the trial will be further explained and informed consent to take part will be obtained. Patients will retain the patient information sheet as well as receive a scoring sheet containing visual analogue scales to assess symptoms - pain, running, sense of smell, bleeding, blockage. A questionnaire assessing use of post-operative analgesia for 7 days on a daily basis will also be included.~All these forms will be on appropriately headed paper. A clear explanation of how to complete the assessment sheet will be given. The patient will be approached again on the pre-operative morning and Patients will be randomised using a randomisation schedule generated by NHS Grampian Research & Development Dept.~can withdraw his/her consent to the trial at any time. Randomisation~Patients will be randomised using a randomisation schedule generated by NHS Grampian Research & Development Dept.~Treatment~Based on the randomisation, patients will be given one of either saline sprays or Sterimar Physiological Sea Water Microspray. Instructions regarding use will be given including frequency and technique.~Outcome measures~On the 3rd and 7th postoperative day, patients will complete the symptom assessment sheet judging their symptoms on that day.~The patient should record painkillers needed on the Analgesia Requirement Sheet on a daily basis for 7 days.~The patients will also be provided with an EQ-5D health questionnaire, which is well validated and has referent look up values for populations of ill and healthy patients.~These will be returned in a pre-paid envelope and will be identifiable only by the patients' study number retained in the randomisation program.~Analysis~Visual analogue scales will be analyzed by investigators blinded to which treatment has been administered.~Results will be further analysed comparing scores achieved for those taking saline sniffs and those taking Sterimar. Tests of statistical significance will be performed to establish if either preparation is superior in symptom control. Analgesia use will be taken into consideration.~To select a difference in symptom scores on a visual analogue scale of 10mm or more at the level of significance with 80% power, a sample size of 60 patients is required in each arm of the trial. This is assuming a standard deviation of 19mm, which was demonstrated in the study previously conducted in this department.

Patients undergoing nasal surgery commonly experience a variety of symptoms in the post-operative period including blockage, running, pain, bleeding and reduction in sense of smell. A variety of preparations are currently recommended for symptomatic relief in the post operative period. These include saline irrigations and sniffs, steam inhalations, decongestants and steroid drops.~There is currently no level 1 evidence in literature to support the use of any particular preparation over others in nasal surgical aftercare.~We propose to conduct a single blinded, randomised trial comparing saline sprays vs Sterimar, a commercially available aerosolised isotone saline solution, comparing patients' symptom scores following septal surgery.~The trial will help to establish efficacy and symptom control and advantages of one solution and delivery device over the other.

There are multiple retrospective studies detailing the use of etomidate in pediatric procedural sedation but few to no prospective clinical trials. None have compared etomidate to ketamine, currently the most commonly used sedative in the emergency department for pediatric procedural sedation. The investigators propose a randomized, controlled trial comparing etomidate versus ketamine for procedural sedation for fracture reduction for children presenting with extremity fracture requiring sedation for reduction. The investigators hypothesize that etomidate in combination with fentanyl will have similar reduction of distress and procedural recall as ketamine in combination with midazolam.

There are multiple retrospective studies detailing the use of etomidate in pediatric procedural sedation but few to no prospective clinical trials. None have compared etomidate to ketamine, currently the most commonly used sedative in the emergency department for pediatric procedural sedation. The investigators propose a randomized, controlled trial comparing etomidate versus ketamine for procedural sedation for fracture reduction for children presenting with extremity fracture requiring sedation for reduction. The investigators hypothesize that etomidate in combination with fentanyl will have similar reduction of distress and procedural recall as ketamine in combination with midazolam.

A comparative evaluation of the pharmacokinetics and pharmacodynamics of two recombinant regular human insulin injections administered subcutaneously in healthy volunteers. It is a crossover study. The subjects shall be administered single doses of each insulin during two separate visits under the conditions of euglycemic clamp.

The purpose of this study is the comparative evaluation of the pharmacokinetics and pharmacodynamics of two recombinant regular human insulin injections administered subcutaneously in healthy volunteers under the conditions of euglycemic clamp.

The ongoing studies in rats indicate that a sympathetically-derived neuropeptide, neuropeptide Y (NPY), potently inhibits the activity of the capsaicin-sensative class of nociceptors (i.e., pain neurons). It is not know whether these results, generated from rodent studies, occur in human tissues under normal or inflamed conditions. We plan to test the hypothesis that NPY inhibits the initiation of neurogenic inflammation, as measured by reduced release of substance P, from capsaicin-sensitive class of petidergic neurons innervating normal and inflamed dental pulp. Such actions would be physiologically and clinically significant, since inhibition of exocytosis from peripheral terminals of nociceptive primary afferent fibers would likely alter neurogenic inflammation, local vasodilation and , possibly pain. Our research strategy takes advantage of a uniquely innervated tissue: dental pulp. Application of any physiologic stimulus to human dental pulp, including thermal, osmotic, chemical or mechanical, produces only pain. Thus, virtually all sensory neurons that innervate pulp appear to be nociceptors. Accordingly, application of drugs to pulpal sensory neurons targets a population of sensory neurons consisting predominantly of nociceptors.~The research questions are as follows:~Determine the capsaicin concentration-response curve from evoking the release of immunioreactive substance P (iSP) from normal and inflamed dental pulp.~Determine the effect of NPY on altering basal and capsaisin-evoked release of iSP from normal and inflamed dental pulp.~We will evaluate the hypothesis that NPY inhibits capsaicin-sensitive neurons in humans using microdialysis probes implanted into anesthetized dental pulp, with release of immunoreactive substance P (iSP) as our dependent measure. This study will include patients who have elected to have a root canal procedure performed or to have a tooth extracted.

Neuropeptide Y (NPY) potently inhibits pain neurons in rats, but does this occur in human pain neurons? This hypothesis will be tested using microdialysis probes in patients who elect to have root canal treatment or extraction of thier tooth.

This is an open-label, parallel group, single-center study. The study design consists of a screening and a treatment period. A total of 42 (approximately 21 of each sex) non-smoking healthy volunteers aged 18 - 35, will be selected for treatment. Potential subjects will be assessed for exposure to ionizing radiation or working with cytotoxic chemicals, or who have cell cycle times that fall outside the range of 13 ± 1.5 hours or subjects with stable chromosomal rearrangements and/or abnormally high background chromosomal aberration frequencies. Approximately 30 subjects (10 per arm) are estimated to be needed for analysis.

This is an open-label, parallel group, single-center study. The study design consists of a screening and a treatment period. A total of 42 (approximately 21 of each sex) non-smoking healthy volunteers aged 18 - 35.

In Emergency Departments (ED) across the nation there is renewed interest in finding ways to alleviate the pain and discomfort associated with many of the procedures that children must undergo. Children's memory and reaction to negative experiences in the care of medical professionals has led to many changes in procedural pain management (4). One noxious procedure that continues to be performed in the ED without the use of anesthetic agents is urethral catheterization (11). In a policy by the American Academy of Pediatrics, a nationally recognized advocate for children, physicians are urged to advocate for child-specific research in pain management and the effective use of pain medication to ensure compassionate and competent management of pain. (AAP Statement, 2001)~Pediatric urethral catheterizations are one such procedure in which children experience significant pain. (11) The Children's Healthcare of Atlanta (CHOA) ED at Egleston performs an average of greater than 150 pediatric urethral catheterizations per month. This procedure is performed in most cases where children under 6 months of age present with unexplained fever. Also, divisional guidelines call for urethral catheterization for urinanalysis and urine culture on all uncircumcised boys under the age of 1 and all girls under the age of 2 who present with unexplained temperature above 39.5 degrees. In a previous Friends funded clinical trial, ED investigators studied sucrose use in children under 2 months of age which was shown to decrease urethral catheterization discomfort. As such, this has become routine care in the ED. (REF; for a review of sucrose for pediatric pain, see 6) In present care, children over 2 months of age do not routinely receive intervention for urethral catheterization related anxiety and pain, and, anecdotal reports suggest that most require physical restraint to complete the procedure.~Lidocaine is an anesthetic agent that provides relief from pain during many commonly performed ED procedures. Examples of present Lidocaine use in the ED are laceration repair, abscess drainage, and lumbar puncture. Given the anxiety, discomfort, and pain associated with urethral catheterizations (1, 2, 3, 4), Lidocaine has begun to be used clinically in this arena. Intraurethral Lidocaine has been shown to decrease pain associated with urethral catheter placement in cystograms, however, Lidocaine is not routinely used for catheter placement to obtain urine in the CHOA ED.~Recently, two specific studies were performed investigating the use of Lidocaine to decrease discomfort associated with urethral catheterization. The first published study supports the use of intraurethral Lidocaine for catheterization.(5) In this investigation, Lidocaine was repeatedly instilled into the urethra of ten 4- to 11-year-old patients for approximately 10 minutes prior to a scheduled cystogram. Patients in this study indicated significantly less pain with Lidocaine as a lubricant when compared to those who received sterile lubricant jelly. However, the placement of a catheter for cystogram requires the catheter to be in place for the duration of the procedure (10 to 15 minutes); whereas catheterization in the ED for urinalysis and urine culture requires catheter placement for a much shorter period of time. The second study, which compared Lidocaine to lubricant jelly used as a topical anesthetic prior to catheterization, found that preverbal patients experienced the same discomfort with or without Lidocaine when evaluated using Face-Legs-Activity-Cry-Consolability (FLACC) scoring.(11) Authors attempted to investigate Lidocaine topically placed at the urethral meatus to provide relief. Although the investigators did not achieve their goal of pain reduction using Lidocaine topically, they did find that the incidence of positive urine culture was similar in both the Lidocaine and placebo groups. Using the strengths of both previously published studies, our study will use Lidocaine both topically and instilled into the urethra.~Medical care professionals are increasing their attention to pain and comfort measures for children undergoing painful procedures in the ED. Pediatric urethral catheterization is one such area that remains unaddressed. The use of Lidocaine as an anesthetic in common ED procedures is well known. Investigation of Lidocaine use as an anesthetic lubricant has been reported twice previously in pediatric literature with contradicting results. After critical appraisal of these studies, our investigators conclude that additional investigation is warranted with the following characteristics: Lidocaine should be placed both topically and instilled into the urethra; Lidocaine should be compared to both routine care and placebo; methodology should include blinded observations; methodology should evaluate pain response utilizing numerous validated tools; and urine should be monitored to evaluate the biological effects of Lidocaine on urine culture results. Investigators aim to demonstrate that Lidocaine used as a lubricant anesthetic for urethral catheterization will provide a safe, time-efficient, and relatively easy way to decrease pediatric pain in the emergency department setting.~Specific Aims & Hypotheses~SA1: To study the potential use of Lidocaine as an anesthetic agent during urethral catheterization of children presenting to Pediatric Emergency Department.~H1: The use of Lidocaine jelly as a lubricant in urethral catheterizations in pediatric ED patients significantly decreases distress associated with this procedure.~SA2: To determine the average Lidocaine concentration present in urine obtained with Lidocaine jelly used as lubricant during urinary catheterization.~H2: Urine Lidocaine concentrations associated with routine urethral catheterization utilizing intraurethral Lidocaine installation will not approach known bacterial growth-limiting levels.

In Emergency Departments (ED) across the nation there is renewed interest in finding ways to alleviate the pain and discomfort associated with many of the procedures that children must undergo. In a policy by the American Academy of Pediatrics, a nationally recognized advocate for children, physicians are urged to advocate for child-specific research in pain management and the effective use of pain medication to ensure compassionate and competent management of pain. (AAP Statement, 2001) Pediatric urethral catheterizations are one such procedure in which children experience significant pain.(11) In present care, children over 2 months of age do not routinely receive intervention for urethral catheterization related anxiety and pain, and, anecdotal reports suggest that most require physical restraint to complete the procedure. Lidocaine is an anesthetic agent that provides relief from pain during many commonly performed ED procedures. Intraurethral Lidocaine has been shown to decrease pain associated with urethral catheter placement in cystograms, however, Lidocaine is not routinely used for urethral catheterizations in the CHOA ED.~This study aims to investigate the potential use of Lidocaine as an anesthetic agent during urethral catheterization of children. Recently, two specific studies were performed investigating the use of Lidocaine to decrease discomfort associated with urethral catheterization. Using the strengths of both previously published studies, our study will use Lidocaine both topically and instilled into the urethra. Investigators plan to perform a prospective three-arm double-blinded randomized clinical trial investigating the effectiveness of Lidocaine jelly as a analgesic when used as a lubricant for urinary catheterization. Investigators aim to demonstrate that Lidocaine used as a lubricant anesthetic for urethral catheterization will provide a safe, time-efficient, and relatively easy way to decrease pediatric pain in the emergency department setting.

Everolimus is a new proliferation signal inhibitor with immunosuppressive and antiproliferative activity.~The mechanism of action of Everolimus is distinct from that of calcineurin inhibitors.~Cardiac allograft vasculopathy is the major cause of late death in cardiac transplant patients.~The different mechanisms of action of Everolimus and cyclosporine suppress immune function in synergistic manner. Thus it is postulated that the use of Everolimus in combination with cyclosporine permits a significant cyclosporine dose reduction without loss of immunosuppressive activity in the clinical setting.~The aim of the present study is to evaluate the evolution of renal function after initiation of Everolimus and minimalisation of CNI dose.

The different mechanisms of action of Everolimus and cyclosporine suppress immune function in synergistic manner. Thus it is postulated that the use of Everolimus in combination with cyclosporine permits a significant cyclosporine dose reduction without loss of immunosuppressive activity in the clinical setting.~The aim of the present study is to evaluate the evolution of renal function after initiation of Everolimus and minimalisation of CNI dose.

To demonstrate that the device is safe and potentially efficacious for use as a left ventricular cardiac assist device for postcardiotomy patients who require hemodynamic support post weaning from cardiopulmonary bypass. Postcardiotomy patients, weaned from a cardiopulmonary bypass system (CPB) in need for hemodynamic support due to ineffective standard medical therapy will be considered for enrollment. An attempt shall be made to reverse the hemodynamic situation with medications (e.g. inotropes, vasopressors). The IMPELLA RECOVER LP/LD 5.0 will be implanted by the surgeon when no improvement in hemodynamics is observed.

To demonstrate that that the device is safe and potentially efficacious for use as a left ventricular cardiac assist device for postcardiotomy patients who require hemodynamic support post weaning from cardiopulmonary bypass.

Despite available behavioral and pharmacological interventions to treat nicotine dependence, most smokers do not utilize these interventions. As such, the vast majority of smokers do not capitalize on potentially effective nicotine dependence treatments. The way in which health risk information is presented may influence interest in a smoking cessation program. In a series of preliminary studies, individuals provided with messages that primed the role of genetic variation in susceptibility to addiction to smoking exhibited positive consequences on intentions to quit (Cappella, Lerman, Romantan, & Baruh, 2005). The proposed study has been designed to examine the effect of a message that primes genetic susceptibility on actual enrollment in a smoking cessation program, actual response to smoking cessation treatment, and potential moderators and mediators of this effect. The results of this pilot study may provide preliminary data for a larger trial and have implications for designing interventions to promote utilization of effective treatments for nicotine dependence among smokers.

The proposed study has been designed to examine the effect of a message that primes genetic susceptibility on actual enrollment in a smoking cessation program, actual response to smoking cessation treatment, and potential moderators and mediators of this effect.

The objective of this trial is to assess the toxicity of thymus transplantation following unrelated umbilical cord blood transplantation. Emphasis will be placed on adverse events that are not typically associated with umbilical cord blood transplantation. Also, to determine whether engraftment of a third party thymus allograft is feasible in patients who have undergone unrelated umbilical cord blood transplantation. Thymic engraftment will be determined by biopsy of the thymus allograft and immunohistochemical evidence of thymopoiesis. In addition, we would like to assess thymic function by measuring the number of naive T cells and the number of T cell receptor rearrangement excision circles (TRECS), and by assessing the diversity of the T cell receptor beta chain. These data will be compared to age, stem-cell donor source and disease matched historical controls whose stem cell transplants were not followed by a thymus transplant. This will be done in descriptive fashion. Other immune parameters will be followed including T, B, and NK cell numbers, T cell responses to mitogens, antigens, and immunoglobulin production.

The objective of this trial is to assess the toxicity of thymus transplantation following unrelated umbilical cord blood transplantation. Emphasis will be placed on adverse events that are not typically associated with umbilical cord blood transplantation. Also, to determine whether engraftment of a third party thymus allograft is feasible in patients who have undergone unrelated umbilical cord blood transplantation.

Recombinant growth hormone (rhGH) treatment is widely used in France to normalize height during childhood and final height in children born small for gestational age (SGA). Because rhGH has been associated with increased insulin levels and insulin resistance, concern has been expressed regarding the late consequences of rhGH treatment on risk factors for diabetes mellitus type II and metabolic syndrome, especially in possibly predisposed subjects as SGA children.~Because rhGH use in this population will sharply increase in the coming years, our purpose is to identify and analyze factors that predispose these children born SGA to the metabolic consequences of rhGH therapy.~The main objective of this study is to identify and analyze factors implicated in the variability of the metabolic and growth responses to rhGH treatment in children born SGA. We want to:~Quantify the metabolic effects of rhGH treatment by analyzing insulin levels, insulin sensitivity and lipid profile (lipolysis and ketogenesis);~Evaluate the effects of two different rhGH regimens on the growth of children born SGA;~Determine if the metabolic effects of rhGH therapy correlate to the growth responses in the two groups;~Identify factors, especially genetic factors, responsible for the variations in individual metabolic and growth-promoting effects of rhGH in children born SGA.~This is a randomized, open-labeled, 2-year study, which will compare two regimens of rhGH therapy on the growth responses and metabolic effects in short children born SGA.~100 prepubertal, non GH deficient, short children (height < -3 SDS) born SGA (birth height < -2 SDS) will be randomized to receive either the recommended dose in the EU of rhGH (Norditropine SimpleXx®), or the dose to achieve a treat-to target value of IGF-1 levels within a +1.5 to +2.5 SDS interval (starting dose, 0.067 mg/kg/day) for 24 months.~Metabolic effects of rhGH treatment will be evaluated by body mass index (BMI), fasting insulin and glucose levels, HOMA index of insulin resistance, insulin and glucose levels during OGTT, HbA1C and fasting serum lipids (free fatty acids, 3-hydroxybutyrate, total cholesterol, LDL and HDL cholesterol, triglycerides). Height, growth velocity, IGF-1 and IGF-BP3 levels will evaluate growth response of rhGH treatment.~Polymorphisms of different genes of the signaling pathway of GH and insulin will be analyzed in order to search for those possibly responsible for the variability in metabolic and growth responses during rhGH treatment in SGA children.

Recombinant growth hormone (rhGH) treatment is widely used in France to normalize height during childhood and final height in children born small for gestational age (SGA). Because rhGH has been associated with increased insulin levels and insulin resistance, concern has been expressed regarding the late consequences of rhGH treatment on risk factors for diabetes mellitus type II and metabolic syndrome, especially in possibly predisposed subjects as SGA children.

Study Objectives and Design: Propofol is a short-acting sedative that is easily titratable, and is approved for use in ventilated patients. The clinical usefulness of continuous intravenous infusion of Propofol has been demonstrated in the management of ventilated ICU patients. In addition, its short duration of action permits repeated neurological assessments to be carried out in patients with neurotrauma.~Despite these benefits, Propofol is not without some drawbacks, including a lack of analgesic effects, dose dependent lowering of blood pressure, and significant expense. To address these issues, the PI developed an ICU Sedation Protocol that combines a titrated continuous infusion of intravenous morphine sulfate with the Propofol infusion to achieve the desired level of sedation. This ICU Sedation Protocol has been approved for use at Scottsdale Healthcare since 2004, and printed copies are available at all ICU nursing stations on the Osborn campus.~At the present time, the ICU Sedation Protocol is used regularly by only two of the five neurosurgeons that care for the neurotrauma patients at the Osborn campus. The remaining three neurosurgeons prefer to use a continuous Propofol infusion with intermittent doses of intravenous morphine sulfate.~The purpose of the study will be to compare the clinical utility of Propofol sedation with and without the use of the ICU Sedation Protocol. Patients will be treated according to the attending neurosurgeons preference. No attempt will be made to influence the patient's routine care and management. The study will compare the average hourly infusion rates for Propofol administration, as well as evaluating the difficulty of neurological assessment, and the ease of weaning to extubation.~This is a prospective, non-randomized, open treatment protocol open to ICU patients at Scottsdale Healthcare Osborn. Only patients with neurotrauma that require intubation will be eligible for enrollment. Patients will be treated according to the consulting neurosurgeons preference. No attempt will be made to influence the patient's routine care and management, as already stated. The choice of sedation type and use of the ICU Sedation Protocol will be at the consulting neurosurgeons discretion.~Involvement in the protocol will cease when continuous intravenous sedation is discontinued for more than 24 hours, the patient is extubated or undergoes tracheostomy, or is transferred from the ICU.

Purpose of Protocol: The purpose of this study will be to compare the clinical utility of Propofol sedation with and without the use of the ICU Sedation Protocol. Patients will be treated according to the attending/consulting preference. No attempt will be made to influence the patient's routine care and management. The study will compare the average hourly infusion rates for the Propofol administration, as well as obtain the nursing staffs evaluation regarding the ease of neurological assessment during each 12 hour shift

The implantable cardioverter defibrillator (ICD) has been shown to be effective in preventing mortality in patients with ventricular tachyarrhythmia. However, the expanding indications of this therapy will have an impact on the follow-up policy. Currently, regular follow-up visits are scheduled every 3 months. In this context, the recently-introduced remote monitoring devices constitute a promising new technique, allowing to transmit information about the status of the device and ICD therapies, without direct contact between patients and physicians. This monitoring by tele-follow-up might reduce the cost of care by avoiding useless visits to the implantation centre.~The aim of our study is to assess the cost-benefit ratio of tele-follow-up assisted care as compared with the conventional ICD follow-up. Thanks to an open label, randomized, 2 arms study : one using a telephone follow up, the other a conventional follow-up.

The implantable cardioverter defibrillator (ICD) has been shown to be effective in preventing mortality in patients with ventricular tachyarrhythmia. However, the expanding indications of this therapy will have an impact on the follow-up policy. Currently, regular follow-up visits are scheduled every 3 months. In this context, the recently-introduced remote monitoring devices constitute a promising new technique, allowing to transmit information about the status of the device and ICD therapies, without direct contact between patients and physicians. This monitoring by tele-follow-up might reduce the cost of care by avoiding useless visits to the implantation centre.~The aim of our study is to assess the cost-benefit ratio of tele-follow-up assisted care as compared with the conventional ICD follow-up.

Prolonged grief disorder (PGD) is a severe psychiatric condition that occurs in about 10% of people who experience a recent loss. PGD does not just go away with time and is associated with considerable functional impairment, physical and mental health problems, lost productivity, lack of interest in previously enjoyed activities, suicide, and depression. Because the majority of people with PGD are elderly and less capable of pursuing outside care, making readily available treatments for PGD is very important. Current treatments for PGD include psychotherapy and antidepressant medications, but there is very little solid research on the effectiveness of these treatments. Previous studies have shown that Internet-based mental health treatments are an effective and cost-efficient way to provide self-help to people who otherwise would not seek care. Using strategies from the psychotherapy known as cognitive behavioral therapy (CBT), this study will evaluate the effectiveness of an Internet-based self-help program in treating people who are at risk for developing prolonged grief disorder following a recent loss.~This is a randomized, wait-list control design. Participants will be randomized to immediately begin the intervention or to wait for 6-weeks before beginning. The intervention will ask participants to log-on to the study's self-help website three times per week for the 6 weeks of treatment. During these sessions, participants will be offered optional information about grief and coping with grief and will be required to complete computer exercises that involve identifying self-care needs, support systems, and short- and long-term goals. Participants will also be asked to perform off-line activities that are designed to increase self-care and social activities and that may take anywhere from a few minutes to 30 minutes per day. For all participants, there will be four assessments, after randomization, before beginning treatment (these 2 are the same for the immediate group), upon completion of the intervention, at 6 weeks post-intervention, at 3 months post-intervention (for immediate group). Assessments will include questions about mental and physical health adjustment, beliefs about the loss, and coping status.

This study will evaluate the effectiveness of an Internet-based self-help program in treating people who are at risk for developing prolonged grief disorder following a recent loss.

This is a Phase 1, randomized, single-blind, placebo-controlled study of five escalating dose levels of SD-101 in healthy male volunteers. The objectives of the study are to assess the safety, tolerability, pharmacokinetic profile, and pharmacodynamics of SD-101. Approximately 40 subjects will participate.~Once subjects have been consented, screened, and assigned to one of the dose levels of SD-101, subjects will receive a single subcutaneous injection of either SD-101 or placebo (PBS) in a ratio of 6:2.~Safety and tolerability will be evaluated by occurrence of adverse events, blood and urine laboratory tests, physical examination findings, vital signs , and electrocardiogram findings. Pharmacodynamics will be evaluated by levels of blood biomarkers and serum cytokines, and flow cytometric cell counts. Pharmacokinetics will be evaluated by levels of study drug in serum.

The main purpose of this study is to assess the safety, tolerability, and biological activity of SD-101 compared with placebo in healthy male volunteers.

Fatty emulsions are an indispensable part of parenteral nutrition, because they deliver energy and essential fatty acids. Furthermore, lipids are involved in the structure and function of cell membranes and receptors, modifying gene expression, and modulating the inflammatory and immune response. In addition, fatty acids are precursors of prostaglandins and other eicosanoids and have therefore important metabolic functions.A promising substrate in the development of lipid emulsions can be seen in fish oils containing solutions. With regard to the current literature, fish oil have a potential benefical influence on the pathophysiological response to endotoxins and exert important modulations on eicosanoid and cytokine biology.~However, there are no studies avaibale comparing fish oil containing fatty emulsions to a lipid emulsion based on olive and soybean oil with regard to inflammatory response and hepatic function.~Therefore, the aim of this study was to evaluate the effects of a new lipid emulsion based ob soybean oil, medium-chain triglycerides, olive oil and fish oil compared to a lipid emulsion based on olive and soybean oil on the inflammatory response and hepatic function in postoperative intensive care unit (ICU) patients.

Lipid emulsions are an essential part of parenteral nutrition, both as a part of energy supply, and as a source of essential fatty acids. It has been shown that the fatty acid composition of cell membranes is influenced by the fatty acid profile of dietary lipids, and may therefore be responsible for modulation of immune response. The aim of this study was to assess the effects of a new lipid emulsion based ob soybean oil, medium-chain triglycerides, olive oil and fish oil compared with a lipid emulsion based on olive and soybean oil on the inflammatory response and hepatic function in postoperative intensive care unit (ICU) patients.

In this single-dose study conducted at a single center, the effect of food on the pharmacokinetics of levofloxacin was studied in 24 healthy men and women aged 18 to 55 years old. Subjects were assigned different treatments based on chance; both the researcher and the study participant knew the treatment being administered. The study consisted of 3 phases: a screening phase, an open-label treatment phase consisting of 2 treatment periods, and a post-treatment phase. Subjects who met the prestudy eligibility criteria were randomly assigned to 1 of 2 treatment sequence groups. In each treatment period, subjects were admitted to the study facility the evening before study drug administration and housed through 48 hours after dosing with study drug. Subjects received levofloxacin as a single oral dose of 500 mg under both fed (within 10 minutes after completion of a high-fat, high-caloric breakfast) and fasted (10-hour overnight fast) conditions according to their randomized treatment sequence. Each dosing day was separated by a washout period of at least 4 days. In each treatment period, pharmacokinetic blood samples were collected immediately prior to dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 10, 14, 24, 30, 36, and 48 hours after dosing for determination of plasma concentrations of levofloxacin. Safety evaluations, including adverse event monitoring, standard clinical laboratory evaluations (hematology, serum chemistry, and urinalysis), vital sign monitoring, and physical examinations were performed on Days 1 and 3 of each treatment period. The post-treatment phase consisted of safety evaluations performed after collection of the final pharmacokinetic blood sampling in the second treatment period. Adverse events were monitored from the time of the first study-related procedure through completion of post-treatment study procedures, or until the time of early withdrawal from the study. Levofloxacin solution administered as 2 single oral doses of 500 mg each, 1 in each treatment period, administered at least 4 days apart.

The main purpose of the study was to evaluate the effect of food on the single-dose pharmacokinetics of an oral solution of levofloxacin.

OBJECTIVES:~Primary~To compare the efficacy of daily administration of naproxen vs placebo in preventing or reducing the severity and duration of pegfilgrastim-induced bone pain (PIBP) in patients with non-hematologic malignancies undergoing chemotherapy.~Secondary~To identify potential risk factors for the development of PIBP.~To identify potential clinical predictors for the response or failure to respond to naproxen in preventing PIBP.~To assess the toxicity of naproxen when administered in the preventive setting.~OUTLINE: This is a multicenter study. Patients are stratified by Clinical Community Oncology Program (CCOP) site. Patients are randomized to 1 treatment arm vs placebo.~Arm I: Patients receive oral naproxen twice daily beginning on the day pegfilgrastim is administered (day 2, 3, or 4) and continuing for 5-8 days.~Arm II: Patients receive matching placebo twice daily beginning on the day pegfilgrastim is administered (day 2, 3, or 4) and continuing for 5-8 days.

RATIONALE: Naproxen may help prevent or lessen bone pain caused by pegfilgrastim. It is not yet known whether naproxen is more effective than a placebo in preventing bone pain caused by pegfilgrastim in patients with non-hematologic cancer undergoing chemotherapy.~PURPOSE: This randomized phase III trial is studying naproxen to see how well it works compared with a placebo in preventing bone pain caused by pegfilgrastim in patients with non-hematologic cancer undergoing chemotherapy.

The Phase 1 clinical study compared the abuse liabilities of Staccato Alprazolam, oral immediate-release alprazolam, and Staccato Placebo in 14 subjects with a history of sedative abuse. Subjects who met the inclusion/exclusion criteria received 2 mg of oral alprazolam and matching placebo over 2 sessions. Those who demonstrated greater liking for alprazolam versus placebo were eligible to participate in the study.

Compare the abuse liabilities of Staccato Alprazolam, oral immediate-release alprazolam, and Staccato Placebo.

The amount of sleep people require depends on many factors, including age, but experts agree that most adults need 7 to 8 hours of sleep a night. People who sleep for shorter or longer amounts of time may be at risk of developing memory problems, heart disease, obesity, and diabetes. The duration and timing of sleep are regulated by an interaction between the circadian pacemaker, or biological clock, and the sleep homeostat, which is an internal account of the amount of sleep a person has received recently. It is unknown whether there is a biological or genetic basis for the amount of sleep a person needs. This inpatient study will examine two extreme sleep groups: short sleepers who sleep 6.5 or less hours a night and long sleepers who sleep 9 or more hours a night. Participants will be exposed to identical sleep opportunities and living conditions. Using hormone analysis to examine participants' circadian rhythms, researchers will evaluate the biological differences that people undergo during the sleep process. Results from this study may help researchers understand whether sleep duration and sleep needs differ among people because of biological and genetic variations.~Over a period of 4 to 6 weeks, potential study participants will attend 4 to 6 screening visits, which will include a medical history review, physical exam, blood and urine collection, electrocardiogram (EKG) to measure electrical activity of the heart, a psychological assessment, and an overnight stay in a sleep laboratory. For 3 weeks, potential participants will also wear an activity monitor, and they will record sleep habits electronically and in a daily diary.~Participants who are eligible for the study will spend 28 days in the Intensive Physiological Monitoring Unit of the Clinical and Translational Sciences Center at the Brigham and Women's Hospital. Participants will not have access to a clock, radio, television, or computer, and they will not be allowed any outside contact. Most days participants will remain in bed for 10 to 14 hours; however, at selected times during the study, participants will remain inactive for periods of 32 to 64 hours and will stay awake for 32 to 40 hours. Throughout the study, participants' sleep patterns will be monitored continuously by a wrist activity recorder. Heart rhythms, brain electrical activity, eye movements, and temperature will also be measured continuously. At different times throughout the study, participants will undergo urine, saliva, and blood collection; alertness, mood, and performance evaluations; and blood pressure measurements. Upon release from the research center, participants will maintain a sleep diary for 3 weeks.

Sleep is necessary for healthy functioning, and people who sleep too little or too much may have an increased risk of developing health problems. This study will examine people who regularly sleep for short or long amounts of time to understand the biological factors that determine how much sleep a person needs.

This pilot study will examine the effects of a norepinephrine reuptake blocker, atomoxetine, on physiological and subjective responses to physical and psychological models of stress and oral amphetamine in healthy volunteers. The physical stress model will be the cold pressor test (CPT) and the psychological stress will be the paced auditory serial addition task (PASAT).~Our overall hypothesis is that atomoxetine treatment, compared to placebo, will attenuate the physiological and subjective responses to stress and d-amphetamine.~2. Research Design: Double-blind, placebo-controlled, within-groups, outpatient study.~3. Methodology: A total of 18 healthy volunteers will participate in this four-week, within-groups, double-blind, placebo-controlled study. The study has two phases separated by a 4 to 15-day washout period. Subjects will be randomly assigned to receive either 40 mg atomoxetine or placebo. For Phase I, subjects will be assigned to atomoxetine or placebo for 4 days. After receiving medication or placebo for three days, subjects will have a 6-hour laboratory session, where responses to physical and psychological stress of a 20 mg/70 kg (20 mg maximum) dose of d-amphetamine will be measured. Several physiological, hormonal, and subjective outcome measures will be obtained during the experimental sessions. Subjects will then have a 4-15 day washout period and will be crossed over to the alternative treatment for Phase II.~4. Findings: Since our last renewal, a total of 16 subjects signed the consent form. Among those, 6 subjects did not return after signing the consent form. An additional 2 subjects were randomized but did not complete the study. One subjects started 3 times was randomized 3 times therefore counted three times in enrollment. Currently still enrolling subjects. (2/7/07)~Have completed this study with 10 subjects, study was published. This study has been entered twice.

A total of 18 healthy volunteers will participate in this four-week, within-groups, double-blind, placebo-controlled study. The study has two phases separated by a 4 to 15-day washout period. Subjects will be randomly assigned to receive either 40 mg atomoxetine or placebo. For Phase I, subjects will be assigned to atomoxetine or placebo for 4 days. After receiving medication or placebo for three days, subjects will have a 6-hour laboratory session, where responses to physical and psychological stress of a 20 mg/70 kg (20 mg maximum) dose of d-amphetamine will be measured. Several physiological, hormonal, and subjective outcome measures will be obtained during the experimental sessions. Subjects will then have a 4-15 day washout period and will be crossed over to the alternative treatment for Phase II.

The purpose of this study is to compare the effectiveness of Cognitive Processing Therapy (CPT) versus Present Centered Therapy (PCT) for male OEF/OIF Veterans with combat related PTSD.~CPT has been shown to be effective in treating trauma survivors in several treatment outcome studies, but utility with Veterans has only been examined with male Veterans in one small pilot study. In addition CPT has never been compared to a treatment as usual or supportive psychotherapy condition to control for the specific and nonspecific elements of treatment. Although Cognitive Processing Therapy is one of the main treatment modalities at several VA's, including Cincinnati, it has never been compared to PCT, nor has it been used in a large, randomized study of male OEF/OIF Veterans. It is hypothesized that individual receiving CPT will show a larger reduction in posttraumatic stress disorder and related symptoms than those individuals receiving PCT.~All male OEF/OIF Veterans will be screened for their appropriateness for the study by phone screen and then by an assessment technician. The Veteran will be assessed at pre, post, 3-month, and 1-year follow-up. The assessment technicians will be blind to the participant's condition. CPT is a 12 week long individual psychotherapy treatment shown to be effective at reducing PTSD and related symptoms for survivors of various types of traumas, including combat. PCT is a supportive counseling treatment that has been utilized as an alternative to waitlist control in VA cooperative studies of PTSD.

The purpose of this study is to compare the effectiveness of Cognitive Processing Therapy (CPT) versus Present Centered Therapy (PCT) for male OEF/OIF Veterans with combat related PTSD.

Obesity is an increasingly important health problem in the United States, particularly among adolescents. Previous studies among adults have shown that people who live in neighborhoods with good walkability and recreational environments have increased physical activity levels, and some studies have suggested that there is a relationship between the neighborhood food environment and eating patterns. While these concepts have been studied in adults, more research is needed on the effect of the neighborhood environment on adolescents. In this study, adolescents who live in select neighborhoods in Seattle-King County, WA and Baltimore-Washington, DC will be enrolled. Forty-eight neighborhoods in these areas will be studied, with researchers taking into account the neighborhoods' walkability levels (e.g., combination of street connectivity, residential density, land use mix, retail floor area ratio) and median income levels. Study researchers will examine and create formulas to measure walkability, pedestrian infrastructure, public recreation space, and nutrition environment quality. Researchers will also examine crime and weather patterns; psychosocial variables; parent support; and perceived neighborhood, school, and home environments. Overall, this study will evaluate the ability of a research model to explain the variation in physical activity levels, sedentary behavior, dietary patterns, and weight among adolescents, with an emphasis on neighborhood environment.~There will be no study visits for this study: participation will take place entirely through the mail, phone, or internet. Participants will include adolescents between the ages of 12 and 16 years old and their parents, all of whom live in the identified study neighborhoods. At the time of study entry, adolescents will complete a questionnaire on neighborhood and safety issues, diet, physical activity habits and places where activity occurs, grades, school policies and parental rules that affect physical activity and eating, and the support they get from people regarding healthy eating and physical activity. One parent of each adolescent will also complete a neighborhood information questionnaire. Adolescents will measure their height, weight, and waist circumference and send the measurements to study staff along with the questionnaire. Next, a 4-week period, study staff will call adolescents on three random days and collect information on their diet in the previous 24 hours. During this period, adolescents will wear an activity meter and a GPS monitor for 7 consecutive days and will mail the devices to study staff for analysis.

Many teenagers have unhealthy eating habits and do not get enough physical activity. This study will examine whether the neighborhood in which a teenager lives affects his/her quality of life, physical activity levels, and eating habits.

This is a randomized study in which two groups will be used to compare the effectiveness of a computerized psychological therapy compared to an information only control group (pamphlet) for reducing fear of dental injections. All patients (96 people with high fear of dental injections) will be tested to assess pre-existing dental fear levels prior to being assigned to study condition. Subsequently, patients in the active treatment group will complete computerized psychological therapy in 1 to 9 weekly 45-minute sessions. Subjects in the control condition will meet with a dental assistant once for approximately 15 minutes to go over a pamphlet. The pamphlet is based on written information developed by a commercial dental web site development company. Following the intervention or control procedures, patients will be reassessed for dental fear using computerized questionnaires. They will also be scheduled to receive a dental injection. Subjects' willingness to complete the dental injection and fear levels during the dental injection will be assessed.

This is a randomized study in which two groups will be used to compare the effectiveness of a computerized psychological therapy compared to an information only control group (pamphlet) for reducing fear of dental injections.

HIV is a virus that can lead to acquired immunodeficiency syndrome (AIDS), a disease that breaks down the immune system and allows for entry of life-threatening secondary infections. HIV is transmitted through the exchange of bodily fluids, primarily through sexual intercourse. Antiretroviral therapy (ART) has proven to be an effective treatment for inhibiting the replication of HIV, allowing for improved quality of life and survival.~Despite the widespread availability and effectiveness of ART, a large number of people with advanced AIDS are not on the therapy, and a number of HIV-infected people die because they are unable to access ART. The Preparing Patients to Start Antiretroviral Therapy (PATH) program is designed to inform patients about HIV treatment and to provide motivation, information, and skills to enhance treatment decision-making. The PATH program may help increase ART use and adherence. This study will develop and test the effectiveness of PATH in helping people with HIV make informed decisions about their healthcare.~This study will be divided into two phases. Phase 1 will last a total of 60 to 90 minutes and will consist of an interview about participants' relationships with friends and family and a medical history. Participants will also provide a blood sample for CD4 count and viral load measurements, returning 1 week later for the lab results. Eligible participants will then be invited to partake in Phase II of the study, which will last 12 months.~Over the 12-month study, participants in Phase 2 will be randomly assigned to Group A or Group B. Group A will be asked to attend at least three individual sessions with a counselor and one group workshop meeting with HIV experts and other people with HIV who have previously been treated with ART. The individual sessions will last 60 minutes and will involve discussion about health care options and information on the latest advances in HIV treatment. The group workshop meeting will last 3 hours and will involve teaching participants about HIV treatment and what it is like to undergo treatment. Participants assigned to Group B will attend one individual counseling session and one group workshop, both of which will cover much of the same information as the Group A sessions. Treatment for Group B will not occur until the last month of the study. Any participants in either group who decide to start taking medications for HIV during the study will be visited monthly by a research assistant who will ask about medications and check medication adherence. Participants will also be expected to check in monthly with the research team.~All participants will complete four 90-minute interviews, occurring at baseline and Months 3, 6, and 12. Interviews will include questions about relationships with friends and family, healthcare and drug-using behaviors, mental state, personal background, and education. All participants will also provide blood samples to measure CD4 count and viral load at Months 6 and 12. Selected participants may be asked to complete an additional exit interview about their opinions surrounding participation in the study.

This study will develop and test the effectiveness of an educational and supportive counseling program called Preparing Patients to Start Antiretroviral Therapy in helping people with HIV make informed decisions about their health care.

Objective: This pilot study will examine the effects of a norepinephrine reuptake blocker, atomoxetine, on physiological and subjective responses to physical and psychological models of stress and oral amphetamine in healthy volunteers. The physical stress model will be the cold pressor test (CPT) and the psychological stress will be the paced auditory serial addition task (PASAT).~Our overall hypothesis is that atomoxetine treatment, compared to placebo, will attenuate the physiological and subjective responses to stress and d-amphetamine.~2. Research Design: Double-blind, placebo-controlled, within-groups, outpatient study.~3. Methodology: A total of 18 healthy volunteers will participate in this four-week, within-groups, double-blind, placebo-controlled study. The study has two phases separated by a 4 to 15-day washout period. Subjects will be randomly assigned to receive either 40 mg atomoxetine or placebo. For Phase I, subjects will be assigned to atomoxetine or placebo for 4 days. After receiving medication or placebo for three days, subjects will have a 6-hour laboratory session, where responses to physical and psychological stress of a 20 mg/70 kg (20 mg maximum) dose of d-amphetamine will be measured. Several physiological, hormonal, and subjective outcome measures will be obtained during the experimental sessions. Subjects will then have a 4-15 day washout period and will be crossed over to the alternative treatment for Phase II.~4. Findings: A total of 10 subjects have completed this study. This study has been published.

A total of 18 healthy volunteers will participate in this four-week, within-groups, double-blind, placebo-controlled study. The study has two phases separated by a 4 to 15-day washout period. Subjects will be randomly assigned to receive either 40 mg atomoxetine or placebo. For Phase I, subjects will be assigned to atomoxetine or placebo for 4 days. After receiving medication or placebo for three days, subjects will have a 6-hour laboratory session, where responses to physical and psychological stress of a 20 mg/70 kg (20 mg maximum) dose of d-amphetamine will be measured. Several physiological, hormonal, and subjective outcome measures will be obtained during the experimental sessions. Subjects will then have a 4-15 day washout period and will be crossed over to the alternative treatment for Phase II.

This study will be a randomized, controlled multicenter trial, conducted jointly by the Indian Council of Medical Research, New Delhi and Family Health International, which will compare three vasectomy occlusion techniques, all using the no-scalpel vasectomy (NSV) approach to isolation of the vas:~ligation and excision of about 1 cm of the vas, with fascial interposition;~intraluminal thermal cautery with excision of about 1 cm of the vas; and,~intraluminal thermal cautery with excision of about 1 cm of the vas combined with fascial interposition.~A total of 1500 healthy, sexually active men at least 21 years old who have chosen vasectomy as a means of contraception will be recruited at four to six study sites in India. The success of the vasectomy procedure will be determined based on semen analysis results. All men should have semen analyses at 8 and 12 weeks post-vasectomy. All men will be asked to attend a final visit at 12 months.

This study will be a randomized, controlled multicenter trial, conducted jointly by the Indian Council of Medical Research, New Delhi and Family Health International, which will compare three vasectomy occlusion techniques, all using the no-scalpel vasectomy (NSV) approach to isolation of the vas:~ligation and excision of about 1 cm of the vas, with fascial interposition;~intraluminal thermal cautery with excision of about 1 cm of the vas;~intraluminal thermal cautery with excision of about 1 cm of the vas combined with fascial interposition.~A total of 1500 healthy, sexually active men at least 21 years old who have chosen vasectomy as a means of contraception will be recruited at four to six study sites in India. The success of the vasectomy procedure will be determined based on semen analysis results. All men should have semen analyses at 8 and 12 weeks post-vasectomy. All men will be asked to attend a final visit at 12 months.

The objective of this observational study is to collect and evaluate data on bronchodilator efficacy and safety of Spiriva® (18 µg tiotropium inhalation capsules) delivered by HandiHaler®, in national sample of Russian patients with varying severities of chronic obstructive pulmonary disease (COPD) in the real life setting over the 8 weeks.~Study Hypothesis:~Primary interest is given to observe change from baseline in post-dose FEV1 after 8 weeks.~Comparison(s):~The objective of this observational study is to collect and evaluate data on bronchodilator efficacy and safety of Spiriva® (18 mcg tiotropium inhalation capsules) delivered by HandiHaler®, in national sample of Russian patients with varying severities of chronic obstructive pulmonary disease (COPD) in a real life setting over the 8 weeks.

At the moment, there is hardly any structured safety and efficacy data collection on Tiotropium in Russia. Therefore, the objective of this observational study is to collect and evaluate data on bronchodilator efficacy and safety of Spiriva® (18 µg tiotropium inhalation capsules) delivered by HandiHaler®, in a national sample of Russian patients with varying severities of chronic obstructive pulmonary disease (COPD) in a real life setting over the 8 weeks.

A Phase 1 study in healthy volunteers to assess the safety and pharmacokinetics of ST20 after oral administration of a single-dose. In addition, a comparison of the pharmacokinetics and exposure of a single dose of ST20 under fasting and non-fasting conditions will be assessed.

A safety and pharmacokinetic study of a single dose of ST20 in healthy volunteers

A single center, randomized, single-dose, open-label, partial-block, four-period, four-way crossover study in 54 healthy adult subjects to evaluate the pharmacokinetics and bioequivalence of sumatriptan delivered by the Intraject system compared to IMITREX STATdose at three injection sites (abdomen, thigh, and arm.)

A study to evaluate the pharmacokinetics and bioequivalence of sumatriptan delivered by the Intraject system.

This is a multi-center, Observational study consisting of a one time survey to assess pain management satisfaction for patients with non-cancer pain. The purpose of this study is to develop a large clinical database for the results of the pain management satisfaction questionnaire. All information collected from hospitals will be used to evaluate patient satisfaction of pain management and to improve the quality of life for patients with non-cancer pain Observational study - No study drug administered

The purpose of this study is to survey pain management satisfaction in patients with non-cancer pain.

This randomized, open-label, six-arm, three-period drug interaction study will recruit 48 healthy volunteers so as to obtain a minimum of 36 evaluable subjects at a single study center in the U.S. The study will have a screening visit, 3 treatment visits for pharmacokinetics (PK) sampling and a follow-up visit. The screening visit will be conducted within 30 days prior to receiving the first dose. Subjects will then be randomized into 1 of 6 treatment groups as shown below:~Cohort Size Period 1 Period 2 Period 3 Sample Days 1 to 7 Days 1-14 Days 1-14~A 8 RTG 400mg BID FPV 1400mg BID FPV 1400mg BID~RTG 400mg BID~B 8 RTG 400mg BID FPV 1400mg BID FPV 1400mg BID~RTG 400mg BID~C 8 RTG 400mg BID FPV 700mg BID FPV 700mg BID~RTV 100mg BID + RTV 100mg BID~RTG 400mg BID~D 8 RTG 400mg BID FPV 700mg BID FPV 700mg BID~RTV 100mg BID + RTV 100mg BID~RTG 400mg BID~E 8 RTG 400mg BID FPV 1400mg QD FPV 1400mg QD~RTV 100mg QD + RTV 100mg QD~RTG 400mg BID~F 8 RTG 400mg BID FPV 1400mg QD FPV 1400mg QD~RTV 100mg QD + RTV 100mg QD~RTG 400mg BID~Study subjects will enter the clinic in the morning prior to dosing and remain at the center for 12 hours following each dose. Fourteen to 21 days following completion of the third dosing period, study subjects will return to the clinic for follow-up assessment. The total duration of the study will be approximately 86 days from screening through follow up. Blood samples for drug concentration measurement of amprenavir (APV) and raltegravir (RTG) concentrations will be collected over 12 hours at the end of each dosing period (at 0 [baseline], 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose). Subjects will undergo a physical examination, CBC with differential, HIV test, hepatitis B/C test, liver function test, renal function analysis, and lipid panel at screening, and all of these tests except those for HIV and hepatitis B/C will be repeated at follow-up post-study. Adverse events and adherence (by pill count and medication diary) will be assessed by the investigator/study personnel at the end of each dosing period. Evaluable patients will be required to have adhered to at least 95% of their study drug doses. Plasma APV concentrations will be analyzed using a validated high-performance liquid chromatography method with tandem mass spectrometric detection (HPLC/MS/MS) and plasma RTG concentrations by triple quadruple mass spectrometry. Plasma APV and RTG pharmacokinetic parameters measured will include maximum concentration (Cmax), time to maximum concentration (Tmax), minimum concentration (Cmin), and area under the concentration-time curve (AUC). All these parameters, except Tmax, will be log-transformed before statistical analysis. Analysis of variance, considering treatment as a fixed effect and subject as a random effect will be performed using Statistical Analysis Software (SAS), and assuming a treatment ratio for steady-state APV PK parameters as 1.0, the 90% confidence intervals will be within the range 0.81-1.24.

To date, no study has investigated whether there is a drug interaction between the protease inhibitor fosamprenavir and the integrase inhibitor raltegravir. COL111242 is a randomized, open-label, 6-arm, 3-period, drug interaction study to assess steady-state plasma amprenavir (APV) and raltegravir (RTG) pharmacokinetics in 48 healthy, HIV-negative adults after administration of a 7-day regimen of RTG 400mg twice a day (BID) alone and after 14-day regimens of unboosted fosamprenavir (FPV) 1400mg twice daily (BID), FPV 700mg/Ritonavir (RTV) 100mg BID, or FPV 1400mg/ritonavir (RTV) 100mg once daily (QD) with and without concurrent RTG 400mg BID. Blood samples for drug concentration measurement will be collected over 12 hours at the end of each dosing period. Subjects will undergo a physical examination, complete blood count (CBC) with differential, HIV test, hepatitis B/C test, liver function test, renal function analysis, and lipid panel at screening, and all of these tests, except those for HIV and hepatitis B/C, will be repeated at follow-up post-study. Adverse events and adherence (by pill count and medication diary) will be assessed by the investigator/study personnel at the end of each dosing period

Ischemia-reperfusion injury, which occurs when the blood supply to an organ, or part of an organ, is cut off and subsequently restored, is an important clinical problem in the organ transplant setting. Diannexin, a recombinant form of the endogenous human Annexin V protein, is in development as a therapeutic agent designed to prevent ischemia-reperfusion injury following organ transplantation. Pharmacology studies indicate that Diannexin has protective effect in various ischemia-reperfusion injury and organ transplantation models. Diannexin binds to phosphatidylserine on cell surfaces, which is believed to underlie its ability to attenuate ischemia-reperfusion injury. In a completed Phase 1 trial, Diannexin was judged safe and well tolerated in healthy adult subjects. The present study is designed to determine the safety and tolerability of single escalating doses of Diannexin in kidney transplant recipients.

The purpose of this study is evaluate the safety and tolerability of Diannexin in kidney transplant recipients.

In HIV-infected women, the use of combination therapy with antiretrovirals (ARV) in pregnancy prevents HIV related morbidity and mortality and prevents mother-to-child transmission of the HIV virus.1 Specifically, suppression of the virus to an undetectable level is important during the delivery of the baby to minimize potential HIV exposure. Commonly prescribed ARV therapy in Ugandan pregnant women includes a combination of two NRTIs, along with a non-nucleoside reverse transcriptase inhibitor (NNRTI), nevirapine. In Sub-Saharan Africa, the use of nevirapine containing regimens is the cornerstone of current ARV therapy, due to an affordable cost, availability in a fixed dose combination pill, and generic availability. Maintaining the efficacy and preventing development of resistance against this agent by the HIV virus is imperative, as second line therapies are often more difficult to obtain, are more expensive, and present more challenges in drug storage in clinics and in the community.~Data have demonstrated that higher exposure to nevirapine is associated with a greater likelihood of achieving virologic control as well as maintaining virologic response over the long term, while sub-optimal drug levels may result in the development of viral resistance.2 The use of combination therapy is important due to the development of resistance seen using single dose therapy with nevirapine at delivery.3 Resistance to nevirapine is particularly worrisome due to the cross-resistance between nevirapine and other NNRTIs, potentially eliminating one essential class of ARVs used to treat HIV. Evaluating nevirapine exposure is also important to avoid toxicities related to excess levels of nevirapine, which may compromise patient adherence to the regimen and put the woman at risk for virologic failure in addition to increased drug toxicity.4, 5~To our knowledge, most studies to date have only evaluated the pharmacokinetics of first dose nevirapine in HIV-infected pregnant women during delivery.6,7 Other studies have had too few sampling times to fully characterize the pharmacokinetic parameters of nevirapine. However, previous studies have demonstrated that pharmacokinetic changes do occur with other ARVs metabolized by a metabolic path similar to nevirapine. For example, one published study demonstrated lower levels of nelfinavir and a disproportionate amount of the nelfinavir M8 metabolite in pregnant women during their third trimester, possibly implicating alterations in the cytochrome P450 enzyme system responsible for both nelfinavir and nevirapine metabolism.8, 9 Given this evidence with similarly metabolized drugs, it is important to definitively characterize nevirapine pharmacokinetics to ensure the safe use of this drug during pregnancy.~Data have also demonstrated a direct correlation between zidovudine intracellular triphosphate concentrations and change in CD4 cell count during therapy as well as a direct correlation between lamivudine intracellular triphosphate concentrations and decline in HIV RNA in plasma.10 Data have also shown that there is a wide inter-patient variability in the concentration of the NRTIs, and adjusting these concentrations based on therapeutic drug monitoring has resulted in improved virologic outcomes for patients.11, 12 No information is known about the intracellular triphosphorylated concentrations of the NRTIs in the pregnant female. We seek to establish if there is a necessity for further evaluation of intracellular levels of all NRTI agents in the pregnant population through this research.~The available pharmacokinetic data to date, have primarily evaluated male populations in the western world. We are just beginning to understand the complex pharmacogenomic mechanisms that play a role in pharmacokinetics and pharmacodynamics. Efavirenz, also an NNRTI, and nevirapine have both been identified as having different pharmacokinetic properties in African patients as compared to American, European, and South American patients.13,14 These changes will play a significant role in the long term efficacy and toxicity of these agents as they are used on a more widespread basis in Sub-Saharan Africa. Evaluating these changes in African women during pregnancy is also essential as females represent the predominant gender impacted by HIV in Sub-Saharan Africa. These changes during pregnancy may impact the safety of these agents in pregnant females if the levels are higher than expected, and may also impact the mother-to-child transmission rate and long term use of these agents if the levels are lower than desired.~Pregnancy adds another dimension to the challenge of treating women with HIV, as the physiologic and metabolic changes can impact the pharmacokinetics of antiretroviral agents. Proposed mechanisms include absorption changes due to prolonged gastric and intestinal emptying time, decreased gastric acid secretion, and increased mucus secretion; increased volume of distribution of drug caused by increased total body water and fat, and decreased plasma protein concentration; changes in elimination related to stimulation of hepatic microsomal enzymes and inhibition of microsomal oxidases; the effects of the fetus including compartmentalization of drugs in the fetus and placenta, biotransformation of drugs by the fetus and placenta, and additional elimination of drugs by the fetus.15,16 Though these physiologic and metabolic changes are known to exist, few trials have evaluated the effect of these factors on the pharmacokinetics of antiretroviral agents and their impact has yet to be demonstrated.~Few pharmacokinetic studies have been undertaken to date in Sub-Saharan Africa, though it is becoming recognized that in order to support the antiretroviral rollout program, these studies are essential for the safe and effective long-term use of these agents. The University of Makerere, Infectious Diseases Institute, is establishing a strong foundation for pharmacokinetic work to take place in Uganda through the development of a pharmacokinetic laboratory which will become the leading resource for pharmacokinetic work in Sub-Saharan Africa. This makes the Makerere University the logical location for this essential evaluation. One of the first studies evaluating pharmacokinetic parameters in African patients was performed by our co-investigators at the Joint Clinical Research Center in Kampala, and established that pharmacokinetic evaluation of these drugs in an African population is both necessary and logistically feasible(22) .~We wish to evaluate if the physiologic changes that occur during pregnancy impact the pharmacokinetics of stavudine, lamivudine, and nevirapine compared to those of a non-pregnant, HIV-infected Ugandan female. Evaluation of drug concentrations at steady state, instead of after a single dose is essential, as most patients are maintained on these medications throughout their pregnancy to ensure complete virologic suppression at the time of delivery. These data are imperative to ensure adequate viral suppression throughout pregnancy and to minimize the likelihood of the development of viral resistance engendered by inadequate drug concentrations

In HIV-infected women, the use of combination therapy with antiretrovirals (ARV) in pregnancy prevents HIV related morbidity and mortality and prevents mother-to-child transmission of the HIV virus.~Specifically, suppression of the virus to an undetectable level is important during the delivery of the baby to minimize potential HIV exposure. In Sub-Saharan Africa, the use of ARV combinations containing nevirapine is the cornerstone of current HIV therapy, due to an affordable cost, availability in a fixed dose combination pill, and generic availability. Maintaining the efficacy and preventing development of resistance against this agent by the HIV virus is imperative, as second line therapies are often more difficult to obtain, are more expensive, and present more challenges in drug storage in clinics and in the community.~Pregnancy adds another dimension to the challenge of treating women with HIV, as the physiologic and metabolic changes can affect levels of antiretroviral agents in the body. Though these changes are known to exist, few trials have evaluated the effect of these factors on the pharmacokinetics of antiretroviral agents and their impact has yet to be demonstrated.~We wish to evaluate if the physiologic changes that occur during pregnancy impact the levels of stavudine, lamivudine, and nevirapine compared to those of a non-pregnant, HIV-infected Ugandan female. These data are imperative to ensure adequate suppression of the HIV virus throughout pregnancy.

Anti CD3 (OKT3): Is an approved drug for intravenous use in the treatment of solid organ transplantation. Preliminary data suggest that the oral administration of OKT3 in low dosages can exert an immune modulatory effect via activation of regulatory T lymphocytes.~β-D glucosylceramide [GC]: Is approved for oral administration and is currently being tested in three clinical trials. Recent data suggested that it can serve as an immunological adjuvant in various clinical settings and to augment the immune response via activation of regulatory T cells.~This clinical trial has been designed to assess the safety of oral administration of OKT3 with and without co-administration of GC in healthy subjects. The use of two potential activators of regulatory T cells, may exert an additive effect, augmenting the systemic immune modulatory effect.

This clinical study is designed to evaluate the safety of oral administration of the study drug anti CD3 (OKT3) in combination with β-D glucosylceramide [GC] .

Primary Study Objectives:~To remove all immunosuppressive therapy from recipients of HLA-identical sibling renal transplants within 24 months of transplantation.~To detect and follow cellular (macro) chimerism of donor hematopoietic stem cell (DHSC) lineages and the generation of T-regulatory cells using specialized immunomonitoring assays for these donor/recipient pairs to demonstrate specific immunologic unresponsiveness.~To investigate the safety and efficacy of a treatment regimen consisting of induction therapy with Campath-1H and steroid-free low dose maintenance immunosuppression, consisting of mycophenolate mofetil (MMF) and tacrolimus converted to sirolimus. This is to be followed by complete withdrawal of immunosuppression beginning at one year, at a minimum, post transplant, in recipients who have also been given four infusions of purified donor hematopoietic Cluster of Differentiation (CD)34+ stem cells (DHSC).

The purpose of this study is to attempt to eliminate the necessity of immunosuppressive therapy for HLA-identical sibling Kidney Transplants, examine cellular chimerism of donor hematopoietic stem cell (DHSC) lineages for pairs to demonstrate immunologic unresponsiveness, and to investigate the safety and efficacy of the treatment regimen including withdrawal of immunosuppression after one year post-transplant for those recipients having received DHSC infusions.

This is an open-label, randomized, single-center, outpatient, unblinded, single-dose, three-way crossover study of the safety and PK properties of Proellex® in women ages 18 - 34 years. Twelve female subjects will each receive a single dose of Proellex®: 25 mg (fed state, formulation A), 25 mg (fed state, formulation B), and 25 mg (fasting state, formulation B); successive dosing will be separated by at least one week intervals from the previous dosing. Blood will be collected prior to taking the dose, and following the dose for 24 hours post-dose. Subjects will be discharged from the study after the last blood sample is obtained after the third dose of Proellex®. Safety will be assessed throughout the study.

An open-label, randomized, single-center, outpatient, unblinded, single-dose, three-way crossover study of the safety and PK properties of Proellex® in women ages 18 - 34 years.

Using dual antiplatelet agents with aspirin and clopidogrel is essential after drug-eluting stent implantation to prevent restenosis and stent thrombosis. However, variable platelet response and potential resistance to therapy have emerged with clopidogrel. Several studies showed that clopidogrel resistance is associated with increased cardiovascular events after coronary interventions. New antiplatelet therapeutic strategy of is needed in case of clopidogrel resistance. We started this study to compare the effect of double dosing of clopidogrel to 150mg per day and adding cilostazol to standard dose of clopidogrel after the insertion of drug-eluting stent in patients with clopidogrel resistance.

To compare the effect of increased dosing of clopidogrel and adding cilostazol to standard dose of clopidogrel after the insertion of drug-eluting stent in patients with clopidogrel resistance

Background Cardiopulmonary bypass [CPB] in small size bodies can result in decreased peripheral perfusion. This results in anaerobic metabolism as evidenced by lactic acidosis. High flow results in systemic hypertension which is accentuated by moderate hypothermia commonly used during cardiopulmonary bypass. Phenoxybenzamine [PBZ] is an arteriolar vasodilator that acts by irreversibly blocking the alpha adrenergic receptors. It causes vasodilatation allowing high flow, low pressure CPB. It has been used extensively outside US in Canada, Europe and Australia. In the US oral PBZ is FDA approved, whereas intravenous PBZ is only available as an investigational drug. At the Cleveland Clinic this medication has been used under this protocol since 1994 in >1000 without any significant or serious adverse outcome. The drug is also used at Texas Children's Hospital, Hospital for Sick Children in Toronto, Children's Hospital of Wisconsin and a number of centers throughout Europe, Australia and Asia. The drug has helped reduce the mortality of children undergoing cardiopulmonary bypass.~The theoretic benefit of PBZ in this patient population is uniform and smooth reduction fo systemic vascular resistance in the perioperative period. This uniform systemic vasodilation allows low pressure, high flow systemic perfusion on cardiopulmonary bypass. We feel that this ins in part responsible for improved outcome after cardiopulmonary bypass, including less end-organ edema formation and dysfunction. Due to experience in this and other centers we strongly believe that the use of PBZ in the bypass management protocol of these patients represents the state-of-the-art and not an experimental investigation. Since in the US the drug is not available except as an investigational drug, we have been required to use it as an investigational new drug [IND] PBZ[oral] is currently used in the US for the management of pheochromocytoma. It has a proven track record and known to be safe. Use in a large number of patients worldwide has shown no serious side-effects except hypotension [which is an effect indeed] requiring norepinephrine [an alpha agonist commonly used after cardiopulmonary bypass in these patients anyway].~Patients~The following patients are candidates for receiving PBZ for HFLPP. These include:~All patients under 16 kg.~Those patients between 16-18 kg whose pre bypass hemoglobin is <16 g/dl~All patients are less than 18 years of age.~Use of Phenoxybenzamine:~Loading dose given at the time of going on CPB:~For patients with obstructing lesions on systemic side:~0.25 mg/kg dose in the bypass circuit~None intravenous~For patients without obstructing left sided lesions:~0.5 mg/kg in the bypass circuit~0.5 mg/kg I.V. at cannulation~Maintenance dose given in the post-operative period:~0.3 mg/kg I.V. every 8 hours till oral intake is started or for first 48 hours~0.3 mg/kg P.O. every 8 hours for next 24 hours~0.15 mg/kg P.O. every 8 hours for next 24 hours and then stop~Hold PBZ if the patient is on norepinephrine infusion or the mean arterial pressure is lower than that allowed for the age group~Do not use maintenance dose in the following patients unless they are on maximum dose of sodium nitroprusside infusion and still hypertensive:~Norwood patients~Fontan patients~Patients with residual left ventricular obstructive lesions - don't use at all in the post operative period~Data collected and monitored for the purpose of this study only:~Demographic information, side effects and mortality data would be recorded and kept in a password protected computer in a secure-access-only physician office. Only composite data without individual identifiers will be reported to the IRB and FDA. No publication is planned from this study and no follow-up will be done after the patient is discharged from the hospital.~Side effects to be monitored:~Hypotension requiring norepinephrine in excess of usual dose [0.2 micrograms/kg/min]~Death from such hypotension in the absence of other causes [such as bleeding, sepsis]~Effects occuring within 12 hours of I.V. dose administration or within 24 hours of P.O. dose administration~Any unanticipated or unusual side effects [none noted since 1994] Consent Informed consent would be obtained from the parents/guardians of all patients. Assent will be obtained from children of >7 years age.

Cardiopulmonary bypass [CPB] in small size bodies can result in decreased peripheral perfusion. This results in anaerobic metabolism as evidenced by lactic acidosis. High flow perfusion results in systemic hypertension which is accentuated by moderate hypothermia commonly used during cardiopulmonary bypass. Phenoxybenzamine [PBZ] is an arteriolar vasodilator that acts by irreversibly blocking the alpha adrenergic receptors. It causes vasodilatation allowing high flow, low pressure CPB. It has been used extensively outside US in Canada, Europe and Australia. In the US oral PBZ is FDA approved, whereas intravenous PBZ is only available as an investigational drug

A three arms, open, randomized interventional study including 100 participants in order to evaluate the cost-efficacy of psychological intervention for strengthening parental authority among parents of diabetic adolescents with poor glycemic control.~Objectives:~The primary purpose of the study is to evaluate the immediate effectiveness and the long run effectiveness of psychological intervention for strengthening parental authority among parents of diabetic adolescents with poor glycemic control.~To evaluate the cost as appose to the benefit of the psychological intervention.~To characterize the different variables in parent's attitude that improve their children's glycemic control.~To develop a therapy model for strengthening parent's authority which will be suitable for parents of diabetic adolescents.~Study design:~All participants in the study will be randomized to three different groups:~A treatment group that will go through psychological treatment to strengthen the parents authority.~A control group that will get an education of a nurse and a dietician~A control group that will not get any intervention. All groups will include parents of diabetic adolescents with poor glycemic control.~The following data will be analyzed during the study:~Changes in glycemic control will be measured by levels of HbA1C.~Changes in the diabetes treatment by the adolescents will be measured by adherence to insulin injections, the number of times a day in which the patient checked his blood glucose values, number of visits in the clinic and psychological questionnaires.~Consumption of health services~Changes in parents attitude and changes in the wellbeing of the diabetic adolescents and their parents will be based on questionnaires.

A three arms, open, randomized interventional study including 100 participants in order to evaluate the cost-efficacy of psychological intervention for strengthening parental authority among parents of diabetic adolescents with poor glycemic control.~All participants will be randomized into three groups:1.The first group will get a psychological treatment in order to strengthen the parent's authority. 2.The second group will get an education of a nurse and a dietician. 3.The third group will serve as a control group and will not go through an intervention.~The following data will be analyzed during the study: 1.Changes in HbA1c. 2.Changes in parents authority. 3.Changes in the diabetes treatment by the adolescents. 4.Consumption of health services. 5.The costs of all psychological treatments.

Extracts of Cimicifuga Racemosa (black cohosh) have been widely used in North America and Europe for decades for the treatment of menopause related problems, either as nutritional supplements or as pharmaceutical products. Previous clinical trials had shown that an extract of Cimicifuga Foetida L.(Ximingting, Luyepharm), which was standardized to have similar components of an extract of Cimicifuga Racemosa, was safe and efficacious to relieve the climacteric symptoms and signs in Chinese women who were recruited according to criteria categorized by theory of Traditional Chinese Medicine.We are interested to know whether it may have the same efficacy and safety profiles when judged with method and standard commonly accepted in western medicine.

This study is designed to determine whether an extract of Cimicifuga Foetida L. is safe and efficacious to relieve the climacteric symptoms of Chinese women

This study will evaluate:~The safety and tolerability of a single dose of VGX-1027 as determined by: adverse event reporting, clinical laboratory results, vital signs, physical examinations, and electrocardiograms (ECGs).~The pharmacokinetic (PK) profile of VGX-1027 maximum concentration (Cmax)

To assess the safety and tolerability of a single dose of VGX-1027 in the range of 1-800mg.

Context: Survival outcome following cardiac arrest in children is poor, and recent evidence suggests that the quality of Cardiopulmonary Resuscitation(CPR) is critically important. Venous blood return to the thorax to refill the heart is essential for good quality CPR and critical organ perfusion. Adult cardiac arrest studies suggest that incomplete chest wall decompression (i.e. leaning on the sternum of the chest) during CPR affects intrathoracic pressure and impedes venous return. The consequence of leaning on the chest during CPR is increased intrathoracic pressure, which creates a back-pressure preventing optimal return of blood to the heart. The critical importance of manipulating positive and negative intrathoracic pressures during Cardiopulmonary Resuscitation (CPR) has been recently demonstrated in both animal and human studies. Food and Drug Administration (FDA) approved defibrillators with a force and depth sensor can monitor the depth, rate and complete release of sternal pressure during CPR. These FDA approved defibrillators have been introduced and implemented in the Pediatric Intensive Care Unit (PICU) at the Children's Hospital of Philadelphia (CHOP). These defibrillators can provide feedback on the force and amount of leaning, but there is no data on the minimal amount of sternal pressure (or leaning pressure) that affects intrathoracic or intravascular pressures or venous return to the heart. In addition, there is no data on how much force on the sternal pressure sensor (e.g. leaning on the sensor) begins to affect intrathoracic pressure in children. We propose to observe, measure and report the effect of incremental gentle sternal pressure increases on intrathoracic pressure, and other surrogates of hemodynamic function, in stable but critically ill and mechanically ventilated children. This study will provide preliminary data to inform the resuscitation research community and assist development of evidence-based pediatric resuscitation guidelines in the future.~Objectives: 1) To characterize the effect of gentle, incremental increases in sternal chest pressure on intrathoracic pressure in mechanically ventilated children. 2) To characterize the effect of gentle, incremental increases in sternal pressure on regional perfusion pressures, when existing catheters (arterial, central venous, intracranial) are present.~Study Design/Setting/Participants: This protocol is a prospective, pilot, observational study in the Pediatric Intensive Care Unit (PICU), Progressive Care Unit (PCU) and the Operating Room (OR)settings at the Children's Hospital of Philadelphia. The participants are a convenience sample of stable mechanically ventilated children from 6 months to < 8 years of age. A total of 20 patients will be enrolled, including a minimum of 10 with vascular catheters.~Study Measures: The primary outcome variable is the change in intrathoracic pressure with incremental increase in gentle sternal pressure, measured by the peak airway pressure detected at the proximal end of the tracheal tube during end inspiration. Secondary outcomes include additional measures of intrathoracic pressure (end inspiratory pressure, mean pressure, area under the curve over 15 seconds, plateau pressure). For patients with indwelling central venous, arterial or intracranial pressure monitors, perfusion pressure changes will also be analyzed.

This protocol is a prospective, pilot, observational study in the Pediatric Intensive Care Unit (PICU), Progressive Care Unit (PCU) and the Operating Room (OR) settings at the Children's Hospital of Philadelphia (CHOP). We propose to observe, measure and report the effect of incremental gentle sternal pressure increases on intrathoracic pressure, and other surrogates of hemodynamic function, in stable mechanically ventilated children. This study will provide preliminary data to inform the resuscitation research community and assist development of evidence-based pediatric resuscitation guidelines in the future.

Cannabis is by far the most frequently used illicit drug worldwide and has significant effects on memory. Further, cannabis has an addictive potential. These effects are mediated by an action of THC, the main psychoactive ingredient of cannabis, on cannabinoid CB1 receptors. These receptors are particularly highly expressed in brain regions involved in memory and reward. Therefore, in this study we will investigate the acute effects of THC on functional brain systems underlying memory and reward. We will visualize these effects using the latest non-invasive imaging technique: pharmacological MRI (phMRI).

The purpose of this study is to determine whether THC, the main psychoactive ingredient in cannabis, affects functional brain systems underlying memory and reward.

It has been demonstrated that photodamage leads to wrinkles, mottled pigmentation, lentigines, telangiectasias, and textural changes, but more importantly, it can also lead to pre-cancerous conditions with the development of actinic keratosis (AK). The majority of photorejuvenation or photodamaged published studies have used 5-Amino-Levulinic acid (5-ALA) as a photosensitizer, and either a blue light or an Intense Pulsed Light source with a 70%-95% global facial skin improvement. The molecular mechanism of such improvement is unknown, but activation of a non-specific immune response in addition to increased fibrosis and new collagen formation, have both been suggested.~Methyl Aminolevulinate ( MAL) is another marketed photosensitizer mainly utilized in Europe. Lipophilicity, higher penetration depth and tumor selectivity has been advocated for MAL compared to 5-ALA. However, its effect in photodamaged skin has not been well documented.~The aim of the study is to determine the efficacy of MAL + Aktilite (PDT) in facial photodamage.~Study Type: Interventional~Study Design: Randomized, double-Blind, placebo-controlled trial. Official Title: A randomized, double-Blind, placebo-controlled trial of Methyl Aminolevulinate + Aktilite in patients with facial photodamage.

The aim of the study is to determine the efficacy of MAL + Aktilite versus placebo + Aktilite in facial photodamage in a randomized double blind trial.

The increased use of epidural anesthesia during labor has lead to an increased incidence of prolonged second stage as an indication for cesarean section or instrumental delivery. The use of oxytocin has proven to be an effective method of augmentation of labor in such prolonged labor cases. However, despite oxytocin augmentation, there has been an increase in the number of cases that require cesarean section or instrumental delivery to effect delivery.~McRobert's maneuver, which is often used in to relieve shoulder dystocia, has recently been shown to increase intrauterine pressure approximately two-fold. However; it is an arduous position for the pregnant woman to maintain over a long period of time. Developing alternative methods to maximize expulsive forces, both uterine contractions and maternal expulsive effort, may be of great value in reducing the number of cesarean sections or instrumental deliveries.~Various researchers have investigated the effect of an occlusal support device (OSD) on the isometric strength of different muscle groups, e.g., neck, back, and extremities. The natural condition of dental occlusion, also known as the index of physical performance, has an affect on both muscle strength and body balance. When occlusal support is given to edentulous individuals they show improved physical exercise ability after the re-establishment of mandibular support. Patients whose dentition is in proper occlusion demonstrate greater endurance of isometric muscle strength than those who are in malocclusion. We hypothesize that optimization of dental occlusion by an OSD may improve muscle strength, leading to increased intrauterine pressure during the second stage in labor.~The aim of our study is to investigate whether the use of the OSD results in a shortened duration of the second stage of labor.

Developing a method to maximize maternal expulsive effort should be of great value in reducing the number of cesarean section or instrumental deliveries. Various investigations have shown that use of an occlusal support device (OSD) increases the isometric strength of different muscle groups. The aim of our study was to investigate the role of an OSD in second stage pushing.

Currently approved erythropoiesis stimulating agents have been used successfully to increase hemoglobin levels, reduce fatigue and other anemia-related symptoms, improve daily function, and alleviate the need for transfusions of red blood cells in subjects with chronic kidney disease-related anemia or in cancer subjects with chemotherapy-induced anemia.~Peginesatide (hematide) Injection is a parenteral formulation for administration by intravenous or subcutaneous injection that is being developed for the correction of anemia in patients with chronic kidney disease, including patients on dialysis and patients not on dialysis, and for the treatment of patients with anemia due to concomitantly administered chemotherapy.~This is a multicenter, open-label dose escalation study to evaluate the safety, tolerability, and efficacy of multiple doses of peginesatide Injection in subjects with refractory non-small cell lung cancer, breast cancer, or prostate cancer. These subjects must have anemia diagnosed as a result of taxane chemotherapy.

The purpose of this study is to determine the safety and tolerability of peginesatide used to treat anemia in subjects diagnosed with recurrent non-small cell lung cancer, breast cancer or prostate cancer and who also receiving a taxane chemotherapy.

Context: Expert recommendations for CPR skills (blowing air into the lungs, pressing on the chest) are poorly followed by health care providers. CPR sensors as small as a hockey puck placed on the chest during CPR delivery are able to coach a rescuer to perform better CPR through corrective voice feedback. More adults survive when the quality of CPR (Q-CPR) is improved. This new technology is currently not approved for use in children, specifically 6 months to < 8 years of age.~Objectives:~Characterize trained pediatric health care provider opinion concerning how appropriate the current Q-CPR sensor (puck), FDA approved for children ≥ 8 years of age, is for use in younger children ages 6m to < 8 years of age.~Determine the need for Q-CPR sensor (puck) size changes to improve its suitability for younger children < 8 years of age, based upon trained pediatric health care provider opinion.~Characterize the amount of Q-CPR sensor (puck) overlap with standard large and small mock defibrillator electrode pads placed in usual locations on the chest.~Evaluate trained pediatric health care provider self-reported willingness to use current or modified Q-CPR sensors (pucks) in younger children, 6 months to < 8 years of age.~Study Design/Setting/Participants: This observational study will be performed in the Emergency Department (ED), Pediatric Intensive Care Unit (PICU), Operating Room (OR) and regular inpatient care area (RIPCA) settings at the Children's Hospital of Philadelphia. Parents and guardians of children ages 6m to < 8 years of age receiving routine clinical care in these patient care areas will be approached for inclusion. Health care practitioners (HCPs) in the ED, OR and PICU will also be approached for inclusion.~Study Measures: Children will have their age, length, weight, and simple measurements of their chest, neck and abdomen taken. The differences in trained pediatric health care provider placement of the compression sensor and their assessment of the suitability / willingness to use the current or size modified sensor will be assessed.

This prospective, pilot observational study will be performed in the Emergency Department (ED), Pediatric Intensive Care Unit (PICU), Operating Room (OR) and regular inpatient care area (RIPCA) settings at the Children's Hospital of Philadelphia. The differences in trained pediatric health care provider placement of the compression sensor and their assessment of the suitability / willingness to use the current or size modified sensor will be assessed.

Background:~Appropriate airway management is the most critical point in pediatric resuscitation and pediatric critical care. It remains, however, a challenge for pediatric residents to learn and retain this critical skill. Recent report from our PICU showed pediatric residents participated only 28% of initial orotracheal intubation, and the rate of the first successful endotracheal tube placement was only 38% of all orotracheal intubation attempt. Repetitive poor-skilled intubation attempts may be associated with complication such as dental or laryngeal contusion, and prolonged intubation attempt may be associated with hypoxia and hemodynamic instability. In order to improve the operational performance in the efficacy (first attempt success rate) and safety (minimizing the associated events which could potentially lead to adverse events), a better training method is warranted.~Objectives:~To test the hypothesis that just-in-time training for pediatric airway management may improve patient safety and operational performance of orotracheal intubation and decreases intubation associated events in pediatric residents in the PICU. To test the hypothesis that high fidelity simulation may enhance the training efficacy and patient safety in simulation settings.~Study Design:~This is a prospective interventional study. During the eighteen months of study period, one of two on-call pediatric residents from 7 south PICU (24 beds) will receive 20 minutes of just-in-time pediatric airway management training. This training will occur before their shift starts before the morning round. This training will cover direct laryngoscopy technique, orotracheal intubation technique, confirmation of the tube placement and recognition of associated events. This training will be done with or without high fidelity simulation function. We will use SimBaby (Laerdal, Norway). The assignment will be randomized. The clinical data of orotracheal intubation are collected through NEAR-4 KIDS registry. Primary outcome is a change in a first attempt success rate by the residents in an overtrained group (7 South PICU) compared to standard training group (7 East PICU). The secondary outcome is the rate of resident participation in orotracheal intubation attempt, the number of intubation attempt before successful intubation by residents and the number of intubation associated events. The videotaped performance during the training is analyzed with Healthcare Failure Mode and Effect Analysis (HFMEA) and will be compared between high fidelity simulation training group and low fidelity simulation training group. The evaluation system developed by HFMEA will be validated by a performance of experienced and non-experienced intubators. Furthermore, the real orotracheal intubation team performance in both PICUs will be evaluated with scale by a research assistant. The demographic and training data of participants of real PICU intubations will be collected. No patient identifiable information will be collected. This data will also be kept in a password-protected research computer.

This is a prospective interventional study to test the hypothesis that just-in-time training for pediatric airway management may improve patient safety and operational performance of orotracheal intubation and decreases intubation associated events in pediatric residents in the PICU. To test the hypothesis that high fidelity simulation may enhance the training efficacy and patient safety in simulation settings.

The importance of touch in physiological development, learning patterns, and stress reduction has been demonstrated in humans and animals through years of research. Based on research which indicates touch therapies provide a significant amount of symptom relief and reduction in anxiety, a growing number of hospitals and clinics are integrating massage therapy into services provided to patients in order to ameliorate many symptoms of diagnosis and/or treatment-related discomfort. Examples are the integrative medicine programs at Memorial Sloan-Kettering Cancer Center and George Washington University Medical Center which include touch therapy modalities. Research focusing on the embodied experience of sensory phenomena such as touch is important to provide the basis for more effective care. No studies to date have focused on the self-reported experience of the cancer patient with regard to what touch means to these individuals, particularly those actively in treatment with intravenous chemotherapy. The embodied sensation of touch in these people is important to understand in order to provide more effective touch-based interventions and also to increase awareness of direct care staff, including nurses, of the profound and complex effect that all forms of touch have on those who are physically and psychically vulnerable. The stress of the diagnosis and treatment heightens patients' awareness of many taken-for-granted aspects of daily interaction, including touching and being touched. The side effects of certain chemotherapy treatments can create neuropathies that make the sense of touch diminished or painful, even to the extent that putting on socks and shoes or taking a pulse or blood pressure can become excruciatingly painful experiences. By allowing people who are actively undergoing treatment for cancer to express the meaning of touch in their lives, a fuller understanding of the multiple dimensions of the experience can be achieved. Using this understanding, more effective nursing and touch interventions can be designed to enhance patient comfort. One author notes a multitude of terminologies to distinguish types of nursing touch in her literature review. She observes that, it is possible that touch is so integral … that the need for serious research is not recognized … it is clear that more research, and qualitative research in particular, is needed to better understand the effects and meaning of touch… (p. 849). Chang (2001) stresses the need to treat physical touch in a holistic way (p. 821) to positively impact the patient. She also stresses the meaning of physical touch is dependent on reciprocal expectations about touch, (p.826). Based on the importance of Chang's delineation of multidimensional aspects of perceptions of touch and the mutual nature of the expectations, additional study is warranted to elucidate the perceptions of touch in patients. This understanding can be used to facilitate increased quality of life in patients with cancer through better education of health care providers and integration of complementary modalities in a safe, effective plan of comprehensive care.~The research design will be a phenomenological qualitative design. The purpose of phenomenological research is the description of the experiential meanings we live as we live them. The research question is the lived experience of adult oncology patients undergoing chemotherapy being touched and touching. The researcher will conduct minimally-structured interviews with a set of follow-up interviews to verify interpretations and ascertain additional participant reflections on the phenomenon of touch.~Data will consist of participant interviews recorded and transcribed by the researcher. Following the methodology of Colaizzi (1978), the interviews are read multiple times to immerse the researcher in each participant's text and achieve a collective impression or feeling for the whole. Following this, significant statements are selected from each interview which pertain to the phenomenon under investigation. Meanings of these statements are formulated hermeneutically (i.e., interpreted) by the researcher. These meanings are then grouped according to themes identified by the researcher. All meanings must be considered. An exhaustive description of the phenomenon under investigation is then written which focuses on the universal, essence that lies on the other side of the concreteness of lived meaning. The researcher then returns to the participants for validation of the meanings, clusters, and descriptions. Finally, new data obtained from participants are incorporated into the structure of the research. Prior to conducting interviews and throughout the entire research process, a log is kept of the researcher's presuppositions about the investigated topic. This acknowledgement of the researcher's viewpoint assists in setting these pre-conceived ideas aside in order to come to direct terms and meanings as lived by the participants. One author's contribution to the methodology comes in his approach to the interpretations of the text. He describes the following components of phenomenological interpretation: 1. turning to the nature of lived experience, 2. investigating the lived experience, 3. hermeneutical phenomenological reflection, 4. hermeneutical phenomenological writing, 5. maintaining a strong and oriented relation, and 6. balancing the research context by considering parts and whole. These interpretive relationships are not linear steps; they form a guideline for all phenomenological reflection and writing.~While the concepts of reliability and validity can not be applied to phenomenological research as they are for quantitative studies, the data trail and decisions regarding interpretation are to be documented fully so that thought processes in the identification of essential themes and meanings can be audited by outside reviewers. Trustworthiness of the data and interpretations is paramount in qualitative inquiry. Lincoln and Guba (1985) set forth four basic concepts to establish trustworthiness: truth value, applicability, consistency, and neutrality. They discuss the divergence of the naturalistic paradigm of qualitative research methods from the traditional or positivist paradigm of cause and effect. The four concepts take on the following respective characteristics: credibility, transferability (which requires contextual similarity), dependability, and confirmability.~The first step of the study is the researcher's articulation of presuppositions regarding the phenomenon of touch. This is carried out throughout the process of the study to ensure the process of interpreting and defining essences of participants' experiences are not unduly influenced by the experience of the researcher. Following approval from the Institutional Review Board, participants will be recruited from physician, nurse practitioner, and physician assistant recommendations at the Regional Oncology Center and other central New York oncology clinics. Each patient will be asked by his or her practitioner if he or she wishes to take part in the study. If the person is interested, his or her phone number will be forwarded to the researcher by the practitioner. The researcher will then contact the patient to confirm his or her willingness to participate and understanding of the aims and procedures of the study. For each patient who is confirmed as desiring participation, the researcher will obtain informed written consent. Participants may withdraw at any time during this study until the interview is transcribed, in order to maintain the integrity of the study. All potential physical, social, legal, and other risks will be described and a phone number given to the participants to contact the researchers in case of questions. Each participant will be interviewed for approximately one hour in a private place and at a time which is convenient to the participant and researcher. Before beginning the interview, the participant will be asked to choose a pseudonym. A second interview will take place several months later (after the researcher has had sufficient time to fully immerse herself in the data). This will give the participants a chance to reflect on their interview and review interpretations of their information made by the researcher. Each interview will be taped and field notes taken by the researcher. These will be transcribed soon after the interview to allow initial impressions to be noted along with interview text. Subjects will be enrolled until saturation is reached (no new data obtained from initial interviews). Due to the need for saturation, the number of interviews can not be planned beforehand; however, the number is estimated to be between 8 and 12 participants. The interviews will be transcribed by the researcher or other transcriptionist. To protect confidentiality, the participants' names will not be attached to electronic or paper data; only pseudonyms will be used as interview and data identifiers. All data will be stored in a locked file container accessible only to the researchers. All audiotapes will be destroyed after completion of the research study. The confidentiality agreements will be kept securely in a separate, locked file cabinet also accessible only to the researchers. Participants' demographic information, including age, gender, ethnicity, educational level, and employment (current or before illness) will be collected and stored with the pseudonym.~Interviews will consist of broad open-ended questions. In order to establish rapport and provide a foundation for more detailed questions, the initial questions will begin with the experience of discovering the cancer, diagnosis, the experiences of treatment, and social and personal consequences of the lived experience. Exploration of the initial diagnosis is important because of the life-changing nature of the diagnosis and the accompanying feeling of shock that many people experience at the moment of receiving the diagnosis (American Cancer Society, 2006). The questioning will then focus on the experience of being touched by others, first during the process of the diagnosis and treatment, then prior to this experience. Questions will also be formulated during the interview on the sensation of touch now and prior to treatment, including touching others. All questions will be broad to allow the greatest possible latitude of participant interpretation; however, a general list of questions will be formulated to ensure consistency and completeness of data collection across participants. In general, the interview is paramount in data collection because it is the intention of the researcher to be minimally intrusive while eliciting descriptions that are robust and complete in describing each person's perspective of the phenomenon. In this study, several broad questions will be asked at some point during each interview to ensure that similar baseline data are collected for each participant. Questions to be asked will be:~Please tell me about some of the changes you have experienced since being diagnosed with cancer.~Please tell me about how you have coped with the diagnosis and treatments.~How have people around you reacted to your diagnosis?~How important to you is being touched?~Has your sense of touch changed in any way since you started chemotherapy?~Has the amount of physical contact you have with others changed?~Have you ever had any massage or other form of touch therapy?~Please describe how it feels to be touched when you are going to the medical clinic or having procedures such as CT scans done.

This study is a qualitative, phenomenological research design. The research question is the lived experience of adult oncology patients undergoing chemotherapy being touched and touching. The researcher will conduct minimally-structured interviews with a set of follow-up interviews to verify interpretations and ascertain additional participant reflections on the phenomenon of touch. The purpose of this study is to describe the sensation of touch in adult oncology patients who are actively undergoing chemotherapy treatment. The primary objective is to identify the essences of multiple meanings of touch to these patients. The importance of touch in physiological development, learning patterns, and stress reduction has been demonstrated in humans and animals through years of research (Field, 2000). Based on research which indicates touch therapies provide a significant amount of symptom relief and reduction in anxiety, a growing number of hospitals and clinics are integrating massage therapy into services provided to patients in order to ameliorate many symptoms of diagnosis and/or treatment-related discomfort. Examples are the integrative medicine programs at Memorial Sloan-Kettering Cancer Center and George Washington University Medical Center which include touch therapy modalities. Research focusing on the embodied experience of sensory phenomena such as touch is important to provide the basis for more effective care. No studies to date have focused on the self-reported experience of the cancer patient with regard to what touch means to these individuals, particularly those actively in treatment with intravenous chemotherapy. The embodied sensation of touch in these people is important to understand in order to provide more effective touch-based interventions and also to increase awareness of direct care staff, including nurses, of the profound and complex effect that all forms of touch have on those who are physically and psychically vulnerable.

Phase I/II, Randomized, Double Blind, Placebo Controlled, Dose Escalating, Safety and Pharmacokinetics Study in Very Low Birth Weight Neonates of Four Doses of BSYX-A110, a Human Chimeric Anti-Staphylococcal Monoclonal Antibody for the Prevention of S. epidermidis Infection will be the first study of BSYX-A110 in the target population of hospitalized, very low birth weight infants. The purpose of this study is to evaluate the safety and pharmacokinetics of escalating doses of BSYX-A110 administered on Study Days 0 and 14.~This will be a randomized, double blind, placebo controlled, dose escalating study of BSYX-A110 in 48 very low birth weight neonates. The dose levels to be evaluated are 10, 30, 60 and 90 mg/kg. Each dose level will enroll 12 infants who will receive two doses of BSYX-A110 or placebo intravenously at a ratio of 2:1 while hospitalized following birth. Infants will be followed for 8 weeks following the first dose of BSYX-A110 or placebo. The primary objective of this study is to evaluate safety and tolerability. The secondary objective is to analyze the pharmacokinetics of BSYX-A110. Positive cultures obtained during the study period will be recorded and analyzed.

Phase I/II, Randomized, Double Blind, Placebo Controlled, Dose Escalating, Safety and Pharmacokinetics Study in Very Low Birth Weight Neonates of Four Doses of BSYX-A110 for the Prevention of S. epidermidis Infection. The purpose of this study is to evaluate the safety and pharmacokinetics of escalating doses of BSYX-A110 administered on Study Days 0 and 14.

Active duty military personnel are at high risk of cigarette smoking. Despite strong efforts by the Department of Defense to reduce tobacco use, rates of smoking among people in the military remain high. The military lifestyle presents unique challenges to implementing smoking cessation programs, including the high mobility of troops, remote locations, and limited access to healthcare services. Because of these challenges, many smoking cessation programs that are effective in the non-military population are often ineffective in the military population. Tobacco telephone quit lines are telephone-based tobacco cessation services that provide easy access to educational materials, referrals to local programs, and individualized telephone counseling. Because tobacco quit lines are remotely based and can fit into varying schedules at convenient times, they may be effective among people in the military. Nicotine replacement patches are another effective smoking cessation tool and can be used in addition to telephone quit lines. The purpose of this study is to evaluate the effectiveness of tobacco quit lines, in addition to nicotine replacement patches, at improving smoking cessation rates among members of the Air Force.~This study will enroll military healthcare beneficiaries who have smoked at least five cigarettes a day in the year before study entry. Participants will be randomly assigned to either a proactive group, in which study researchers will initiate contact with the participants, or a reactive group, in which participants will initiate contact with the researchers. In this six-session program, phone calls will occur at 1- to 2-week intervals over an 8-week period. The phone sessions will focus on cutting down on cigarette smoking, setting a quit date, and relapse prevention. All participants will receive nicotine replacement patches after the second session is completed. The reactive group will receive two weeks of nicotine replacement patches and the proactive group will receive 8 weeks of nicotine replacement patches. At the end of session four and 1 year later, study staff will call participants to collect information on tobacco abstinence, nicotine replacement patch use adherence, and other smoking cessation medication use.

Rates of cigarette smoking in the military are high. Tobacco telephone quit lines are telephone-based services that provide information and guidance to people who want to quit smoking. This study will evaluate the effectiveness of a tobacco quit line program, in addition to nicotine replacement patches, at helping people in the military quit smoking cigarettes.

Approximately 12% of women smoke during pregnancy, and at least 500,000 babies are born each year having been exposed to nicotine. These infants have poor lung function at birth and have an increased risk of developing lung diseases, including bronchitis, pneumonia, and asthma. Researchers believe that nicotine may interact with nicotinic receptors in the unborn child's developing lungs and cause altered growth and decreased lung function. Preliminary animal research studies suggest that some of the harmful effects of nicotine may be blocked by vitamin C, an antioxidant that may protect against cellular damage caused by nicotine and other pollutants. The purpose of this study is to evaluate the effectiveness of vitamin C at blocking the harmful effects of nicotine exposure on lung development and function in children born to women who smoke during pregnancy.~This study will enroll pregnant women who smoke, as well as a control group of pregnant women who do not smoke. At a baseline study visit, all participants will complete smoking history questionnaires. For 2 weeks, all participants who smoke will receive placebo capsules once a day. They will then be randomly assigned to receive either vitamin C capsules or placebo capsules, both of which will be taken once a day, in addition to a prenatal vitamin, for the duration of their pregnancy. Study visits, occurring once a month throughout the pregnancy, will include a medical and smoking history review and urine collection. An ultrasound exam will be performed once during the pregnancy to determine the exact size and age of the baby, and blood collection will occur at baseline and once or twice more during the pregnancy. Study researchers will review participants' medical records and will call participants three times during their pregnancy to review their food intake. At the time of delivery, amniotic fluid samples will be collected. When babies are 48 hours old, baby lung function testing will occur, and when babies are 3 and 9 months of age, researchers will call participants to collect breathing information on the babies. When babies are 12 months old, participants will attend a study visit that will include urine collection from the babies and a review of baby breathing difficulties, medication changes, and environmental smoking exposure.

Women who smoke during their pregnancy place their unborn child at an increased risk of health problems, including decreased lung function and possible lung diseases later in life. Preliminary animal research suggests that if vitamin C is taken during pregnancy, nicotine's harmful effects on the unborn baby's developing lungs may be blocked. This study will determine the effect that vitamin C has on the lung development and function of babies born to women who smoke during pregnancy.

Falls among hospital patients are a persistent problem, with 2.3 to 7 falls occurring in U.S. hospitals every 1000 patient days. Approximately 30-48% percent of these falls result in injury and 5 to 10 percent of them result in serious injury. Fall related deaths occurred at a rate of 46.2 per 100,000 in 2003. Hospital falls affect both young and old patients and many of them occur when the patient is alone or involved in elimination-related activities. Falls that result in injury may lead to an extended hospitalization and increased costs . Patients who fall and sustain injury are reported to have hospital charges of more than $4,200 higher per admission than patients who do not fall. Hourly nursing rounds have been shown to decrease falls by 52% .~Hospitalized patients often require assistance with basic self-care tasks, such as using the toilet, ambulating, and eating; they ask for assistance by using the call light. Therefore, a patient's level of satisfaction with nursing care depends principally upon the patient's perception of how well the nursing staff has been able to meet his or her needs. The call light can be a lifeline for hospitalized patients, but it can also impose considerable demands on nurses' time. Several studies have documented the unfavorable effects of patients' frequent use of call lights on the effectiveness of patient-care management on inpatient units, which may already be compromised by staffing shortages.~Current data at Crouse Hospital show that the fall rate on 4S is 5.05 per 1000 patient days, demonstrating significant opportunity for improvement. Data from the 6S shows a fall rate of 5.26 per 1000 patient days. As far as patient satisfaction, the percentage of patients who gave the 4S a 9 or 10 out of a possible score of 10 for overall rating of care was 56.29%. Likewise the number of patients who would definitely recommend Crouse Hospital to others was 56.25%. Both satisfaction questions (Core IP Key Results: I would prefer to return to X without hesitation, if care is needed and I would recommend X without hesitation to others) show significant opportunities for improvement. Preliminary call light usage gathered from the Hill Rom call light system, which is currently available only on 6S, showed 6,909 individual uses of the call light within a 4-week period. One can surmise from this number that patient issues are not being addressed in a timely manner and therefore significant opportunities for improvement exist. Only aggregate data will be collected. No subjects will be identified directly or through any identifiers.~The objectives of the study are to:~Correlate the effects of hourly nursing rounds, if any, to patient falls and call light use.~Determine if there are any changes in patient satisfaction levels~All subjects 18 years and over admitted to 4 South Irving (Oncology/OBGYN) or 6 South Irving (Orthopedic/Neurology) during the twelve month study will be included as research subjects.~Exclusion Criteria: Any patient not admitted to 4 South Irving or 6 South Irving at Crouse Hospital will be excluded from the study. Patients under the age of 18 years are not admitted to these units.~Sample sizes for the study were determined for call light usage rates, patient satisfaction scores, and fall rates. Current process averages for sample size calculations were obtained as follows: 1) fall rates from existing fall rate reports 2) patient satisfaction from Avatar surveys, and 3) call bell usage from preliminary Hill Rom system data. For all sample size calculations, α=0.05 and β=0.10 were used. Based on these calculations, the study baseline data for patient satisfaction will be calculated using Avatar patient satisfaction data from the six-month period prior to study initiation. The baseline data for falls will be collected from existing fall rate reports using the six months of data prior to study initiation. Data for these variables will continue to be collected for 6 months after the implementation of nursing rounds. For call bell usage rates the data for 2 weeks prior to rounding implementation will be collected as baseline data. Data will be collected for 4 weeks following the implementation of nursing rounds. Data for average patient age, length of stay, and severity of illness for both units will be obtained from Transition Systems, Inc. TSI, a financial data base is a type of Decision Support System. In order to get the information on a patient's age a query will be made of TSI. It will then print up average ages of a particular unit within a specified time. Measures of central tendency and spread will be calculated for these variables to compare both units. Chi-square tests, rank sum tests, and tests of means will be used to compare baseline and post-intervention demographic characteristics and reasons for call light usage on both units. Rate ratios comparing post- to pre-intervention fall rates and call rates will be calculated on both. For both fall rates and call rates, significance tests will be conducted to determine whether the rate ratios differ between the two units. The change in the proportion of patients who indicated they were satisfied with their care in each unit before and after the intervention will also be calculated and compared. The data will be analyzed using SAS®9. No data involving individual patient identifiers will be presented with the analysis. Findings from this study will potentially be used to change nursing practice at Crouse Hospital.~4-South Irving, the experimental unit, will be used as its own control. A second unit, 6S, will maintain current practices and data from this unit will be used to determine if there are any hospital-wide fluctuations for fall rates, patient satisfaction, or call light usage. Age, gender, and severity of illness of subjects on the control and experimental units will be compared. Because the patient populations differ from the experimental to control unit, the reasons why patients use the call light will be collected to verify that these two groups use the call lights for similar reasons.~The principal and co-investigators of this study will be educating all nursing personnel on both units on how to collect and document call light data 1 week prior to the start of the data collection process. Baseline call light data for the reasons why patients use the call light and number of patient calls will then be collected for 2 weeks. After baseline call light data are collected the principal and co-investigators will be educating all nursing personnel on 4 South Irving on how to round on patients. Education will last for 2 weeks and includes what questions to ask of the patient while in the room, what tasks need to be done each time they are in the room, when to round on patients, and how to document rounds. An hourly rounding toolkit purchased from the authors of the original study, which includes an educational video, will be used to assist in this education phase. Nursing leadership, which includes the nurse manager, Director of Medical-Surgical Nursing, the Chief Nursing Officer and Clinical Nurse Specialists, will be educated on techniques to ensure rounding is consistently completed by nursing personnel. The implementation of nursing rounds will begin after the two weeks of rounding education is completed.~One member of the nursing staff, including RNs, LPNs, and Nursing Assistants, will be required to perform nursing rounds every hour on 4 South Irving Patients will not be awakened if they are sleeping unless it is necessary for treatment. During nursing rounds, nursing personnel will assess pain levels using a pain-assessment scale, offer toileting assistance, assess the patient's position and position comfort, make sure the call light is within the patients reach, put the television remote control and bed light switch within the patients reach, put the bedside table next to the bed, put the tissue box and water within the patient's reach and prior to leaving the room ask Is there anything I can do for you before I leave? I have time while I am here in the room. Nursing personnel will also tell the patient that a member of the nursing staff (name will be written on white board in room) will be back in an hour to round again. Nursing staff members are expected to complete all patient-care tasks, unless they are not authorized to dispense medication or work with IVs. Laminated pocket cards will be given to nursing staff so they are continually reminded of the actions to perform on the rounds. Patients will not be awakened to check for pain, positioning, or the need to use the bathroom; however the environmental check can be completed during rounds. Members of the nursing leadership team including the nurse manager, Director of Medical-Surgical Nursing, Chief Nursing Officer, and Clinical Nurse Specialists will be making frequent observations of staff, using rounding documentation sheets and patient interviews, to verify that rounding is occurring as expected.~Call light usage will be collected through the use of the Hill Rom call light system. Recently, Hill Rom Beds were added to 4 South. Now the two units are equipped with Hill Rom Beds and corresponding Hill Rom call lights. All call lights placed from individual patient rooms are recorded on a central server located in each nursing station. The central server can generate and print reports for all call lights used in a user specified time frame. Reports include the time a call light was placed, area it was placed from and call light response time. Reasons for call light usage will be documented by bedside nursing personnel on a standard sheet. The documentation forms will be collected every day at 7a.m. by the principal investigator or co-investigators of the study. New documentation forms will be posted daily at 7a.m. Inter-rater reliability will be performed by comparing manual call light data to the computerized call light data collected within the Hill Rom call light system. Documentation of rounding times and frequency will also be documented by nursing personnel on a standard form . This form will be collected every day at 7a.m. by either the principal investigator or co-investigator of the study. New rounding documentation forms will be posted daily. Rounding documentation forms will be used to calculate the percentage of rounds completed as expected.~On both units, baseline data collection for falls and patient satisfaction will be collected for 6 months prior to the start of nursing rounds and 6 months after the start of the implementation of nursing rounds. Fall rates will be collected through pre-existing fall rate reports and reported as falls per 1000 patient days. Patient satisfaction will be collected through pre-existing Avatar patient satisfaction surveys that are randomly sent to discharged patients. All data will be analyzed to determine if statistically significant differences in patient fall rates, satisfaction, or call light usage occurred.~A limitation in this study is that nurses from the medical surgical float pool may work on 4 South and subsequently be assigned to 6 South within the 6 month post-intervention time period. This potential movement of nurses between the control and experimental unit may influence the results on the control unit. This will be addressed by limiting the number of float pool nurses who are scheduled to work on both the experimental unit and the control unit for the six months following the education phase of the study.

The purpose of this study is to determine the effects of hourly rounding on patient falls, patient satisfaction, and patient call light usage. This is a replication of research which determined that hourly rounds conducted by nursing personnel decreased patient falls and call light usage and increased patient satisfaction. The study design is quasi- experimental. One unit will be used as its own control (4S). On this unit, hourly nursing rounds will be implemented by Registered Nurses, Licensed Practical Nurses, and Nursing Assistants. A second unit, 6S, will maintain current practices and data from this unit will be used to determine if there are any hospital-wide fluctuations for fall rates, patient satisfaction, or call light usage. Data for patient falls, patient satisfaction, call light usage, and reasons for call light use will be collected on both units using fall rate reports, patient satisfaction survey data, and the call light system.~Falls among hospital patients are a persistent problem, with 2.3 to 7 falls occurring in U.S. hospitals every 1000 patient days. Approximately 30-48% percent of these falls result in injury and 5 to 10 percent of them result in serious injury. Fall related deaths occurred at a rate of 46.2 per 100,000 in 2003. Hospital falls affect both young and old patients and many of them occur when the patient is alone or involved in elimination-related activities. Falls that result in injury may lead to an extended hospitalization and increased costs. Patients who fall and sustain injury are reported to have hospital charges of more than $4,200 higher than patients who do not fall. Hourly nursing rounds have been shown to decrease falls by 52%.~Hospitalized patients often require assistance with basic self-care tasks, such as using the toilet, ambulating, and eating; they ask for assistance by using the call light. Therefore, a patient's level of satisfaction with nursing care depends principally upon the patient's perception of how well the nursing staff has been able to meet his or her needs. The call light can be a lifeline for hospitalized patients, but it can also impose considerable demands on nurses' time. Several studies have documented the unfavorable effects of patients' frequent use of call lights on the effectiveness of patient-care management on inpatient units, which may already be compromised by staffing shortages.

The purpose of this study is to determine the pharmacokinetics profile of ceftaroline in pediatric subjects

The purpose of this study is to determine the pharmacokinetics of ceftaroline in pediatric subjects

Apatinib is a tyrosin-inhibitor agent targeting at VEGFR (vasoendothelial growth factor receptor) to inhibit tumor angiogenesis. The anti-angiogenesis effect of apatinib has been viewed in preclinical tests (see protocol). This phase I clinical study is going to evaluate its toxicity and to find an appropriate dose level to be used in a phase II study in heavily treated solid tumor patients.

Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), so it can inhibit tumor angiogenesis. This phase I study aims to determine the drug's toxicity and to find a dose level to be used in a phase II study in solid tumor patients.

Radiostereometric Analysis, or RSA, is an accurate in vivo measurement technique using two simultaneous radiographs. It provides researchers with three dimensional motion analyses to look not only at routine flexion/extension, but also other rotational and translational changes. The measurement accuracy offered by this technique far exceeds the manual techniques currently used. Utilization of the RSA technology at the IHP and the United States is in its infancy. The investigators have placed much effort over the past 2-3 years to put the necessary dedicated resources and personnel in place. This has been a collaborative effort between the Department of Orthopedic Surgery and the Imaging Core at IHP. Preliminary work on the accuracy, reliability, and surgical planning for use of RSA has been completed and presented at national conferences.~The purpose of this study is to assess the amount of motion in the lumbar spine in patients with the AST Stabilimax BAR. The AST Stabilimax BAR is designed to allow for motion in the spine while providing the necessary stability to the spinal segment. The amount and degree of this motion is currently unknown clinically, but has been biomechanically tested in vitro. By using tantalum bead markers placed in the spine at the time of the surgery, RSA analysis can determine the amount and degree of motion the implant provides. Two questions will be examined with this data: 1) what is the amount of sagittal and coronal plane motion that occurs in vivo with the AST Stabilimax BAR system? and 2) will this change over the 2 year time frame for this study?

Assessment of segmental spine motion has been and continues to be, a difficult clinical problem. Errors of up to 10 degrees for simple measurements of flexion, extension and side bending have been recorded using conventional radiographs (xrays.) These errors are usually associated with the inability to acquire three-dimensional positions and inaccurate reference points. It has, therefore, been extremely difficult to measure small changes in vertebral alignment, which may prove to be an early, clinically significant, indicator of potential problems. Radiostereometric Analysis, or RSA, is an accurate in vivo measurement technique using two simultaneous radiographs. It provides researchers with three dimensional motion analyses to look not only at routine flexion/extension, but also other rotational and translational changes. The measurement accuracy offered by this technique far exceeds the manual techniques currently used. The purpose of this study is to assess the amount of motion in the lumbar spine in patients with the AST Stabilimax BAR. The AST Stabilimax BAR is designed to allow for motion in the spine while providing the necessary stability to the spinal segment. The amount and degree of this motion is currently unknown clinically. By using tantalum bead markers placed in the spine at the time of the surgery, RSA analysis can determine the amount and degree of motion of the implanted construct. Two questions will be examined with this data: 1) what is the amount of sagittal and coronal plane motion that occurs in vivo with the AST Stabilimax BAR system? and 2) will this change over the 2 year time frame for this study?

For many women, college is a time of great change that affects one's social and behavioral practices, including sexual behavior. The first part of the NuvaRing ® Acceptability study is an online survey, developed in conjunction with the University of Illinois's Survey Research Laboratory, which examines women's attitudes and beliefs regarding various methods of birth control. The second part of the study is a comparison trial in which the women are randomized to either the NuvaRing ® vaginal contraceptive ring or a low dose oral contraceptive. The women are followed for three months to assess compliance, side effects, overall acceptability and intent to continue use of the method. Ultimately, we would like college women to be well informed about various methods of contraception available to them and to choose the contraceptive method that best suits their lifestyle.

The ACCEPT study is a Phase IV trial in which women are randomized to either the NuvaRing® vaginal contraceptive ring or a low dose oral contraceptive to assess compliance, side effects, overall acceptability and intent to continue use of the method. The study is focused on the acceptability of the vaginal ring among female undergraduate or graduate students.

Objective: To determine the effect of maternal hydration with oral isotonic solution and water on amniotic fluid (AF) index in women with normohydramnios.~Subjects and Methods: Women with normal AF index and gestational age between the 33 and 36 weeks without maternal complications were randomized into three groups (isotonic solution, water, control). The isotonic solution and water groups were instructed to drink 1.5L of respective solution; the control group was instructed to drink 200mL of water. AF index was measured before and after hydration. The investigator performing the AF index was blinded to the subject's group.~Results: Ninety-nine women completed the study without any maternal adverse effects. The mean increase in amniotic fluid index after hydration was significantly greater in the isotonic solution and water groups (12.1mm, p=0.02; 13.1mm, p=0.05; respectively) than the control group (1.4mm, p=0.74). There was no significant difference between the isotonic solution and water groups. Hydration with isotonic solution and water improved the chance of 20% of increase of amniotic fluid index in 10.2 (95% CI 1.9-98.9) and 6.0 (95% CI 1.0-45.5) times respectively.~Conclusion: Maternal hydration with isotonic solution or water increased AF index in women with normohydramnios.

The purpose of this study is to determine the effect of maternal hydration with oral isotonic solution and water on amniotic fluid (AF) index in women with normohydramnios.

- list item one ß-C in yellow maize~Pro-vitamin A carotenoids in plants are a major and safe vitamin A source for a vast population in the world. Even though, ß-carotene (ß-C) in vegetables has been considered as a safe vitamin A source, it is essential to determine the efficiency of provitamin A carotenoids in plant conversion to vitamin A. However, the bioavailability of vitamin A and carotenoids from food matrices has not been well studied due to the unavailability of isotopically labeled foods that can be fed to humans.~The main objective of this study is to investigate the bioavailability of ß-C in yellow maize and its bioconversion to retinol stored in the liver using stable isotope labeled high ß-C yellow maize and vitamin A in a well-nourished population by utilizing stable isotope dilution techniques. In this project, the deuterium labeled vitamin A that is derived from the labeled ß-C yellow maize will be traced after being eaten by a human subject. This will allow for quantitative determination of the vitamin A equivalence of high ß-C plant foods.~Eight men (> 40 years and < 70 y) who are healthy, non-smoking adults must have their body weight within 20% of standard weight for height (Metropolitan) and not having taken vitamin A or ß-C supplements within the last month will be recruited as volunteers.~This is a 50 day study during which dose 1, cooked labeled yellow maize paste (porridge) equal to a total of ~ 2 bowls cooked yellow maize (from 100 - 200 g dry weight) containing ~ 1 mg ß-C will be taken by each volunteer. On day 8, dose 2 will be used in evaluation of liver storage of vitamin A using 1 mg of 13C retinyl acetate. One blood sample (20 cc) will be drawn during the screening process. Forty six blood samples (460 cc) will be taken during the study which will be analyzed for serum carotenoids and retinoids using HPLC and mass spectrometry techniques. The serum concentration and isotope ratio of ß-C and retinol will be determined. Serum enrichment curve following each oral dose will be studied. The area under the curve (AUC) of retinol-d4 and labeled retinol from the reference dose in serum samples will be determined and compared. The equivalence of a high ß-C plant food supplement to a vitamin A dose will be calculated based on the isotope reference method.

The study hypothesis is that high ß-C yellow maize can provide vitamin A efficiently.~- list item one ß-C in yellow maize~The study will use stable isotope labeled high ß-C yellow maize and vitamin A in a well-nourished population by utilizing stable isotope dilution techniques. In this project, deuterium labeled vitamin A that is derived from the labeled ß-C yellow maize will be traced after being eaten by a human subject. Eight men (> 40 years and < 70 y) who are healthy, non-smoking,body weight within 20% of standard weight for height (Metropolitan) and not having taken vitamin A or ß-C supplements within the last month will be recruited as volunteers. This study will last for 50 days during which at day 1, cooked labeled yellow maize paste (porridge) equal to a total of ~ 2 bowls cooked yellow maize (from 100 - 200 g dry weight) containing ~ 1 mg ß-C will be taken by each volunteer. On day 8, a labeled vitamin A (1 mg of 13C retinyl acetate) in oil dose will be used in evaluation of liver storage of vitamin A. Forty six blood samples (460 cc) will be taken during the study which will be analyzed for serum carotenoids and retinoids using HPLC and mass spectrometry techniques.~The serum concentration and isotope ratio of ß-C and retinol will be determined. Serum enrichment curve following each oral dose will be studied. The area under the curve (AUC) of retinol-d4 and labeled retinol from the reference dose in serum samples will be determined and compared. The equivalence of a high ß-C corn meal to vitamin A will be calculated based on the isotope reference method to determine the efficiency of corn ß-C to provide vitamin A.

- list item one, Peppers~Epidemiological data show that carotenoids and ß-C are health promoting when taken at physiologic levels in foods. However, human absorption and metabolism of carotenoids contained in various food matrices has not been studied well. It is important to investigate the characteristics of absorption and disposal kinetics after eating carotenoid rich foods in order to gain a basic understanding of the biological characteristics of lutein, zeaxanthin, and other carotenoids in food sources.~We propose to evaluate bio absorption of pepper carotenoids in a 2-phase research study: phase 1 will utilize red bell-pepper and phase 2 will utilize non-pungent green jalapeno pepper. The pepper will be provided as a dish in a meal. We will feed 16 healthy man and women (50 - 70 y, females were at least one year post menopause), each with red pepper (phase 1) and/or green jalapeno pepper (phase 2) for ~ 4 days and donate blood samples up to 21 days. Volunteers will be randomly assigned to one of the following two phases: phase 1 and phase 2.~The study will provide us the information on the bioavailability of pepper carotenoids.

- list item one, Peppers~We propose to evaluate bio absorption of pepper carotenoids in a red bell-pepper or non-pungent green jalapeno pepper. The pepper will be provided in a cooked dish. The specific aims of this study are: 1) to determine blood response kinetics of lutein following multiple doses of non-pungent green jalapeno pepper with meals. 2) to determine blood response kinetics of zeaxanthin/capsanthin following multiple doses of red bell pepper with meals. We will feed 16 healthy man and women (50 - 65 y, females were at least one year post menopause), each cooked green jalapeno pepper or red pepper for 4 days and donate blood samples up to 21 days to determine blood response kinetics of xanthophylls following multiple doses of pepper dishes.

Although gastrointestinal endoscopy is widely accepted as fundamental to the diagnosis and treatment of digestive disorders in children, considerable controversy and practice differences persist with respect to the methods and agents used to achieve optimal endoscopic sedation.~Comparison:oral midazolam vs midazolam IV in sedation and comfort scale of pediatric endoscopy.

The objective of our study was to compare the safety and efficacy of oral midazolam during pediatric endoscopy.

Determine the antimicrobial properties of a proposed new product and an already approved product and a placebo (no drug). Study will be conducted using methods dictated by the FDA.~This study uses topical sampling from the abdomen and the groin on intact skin and evaluates the germs left on the skin after treatment with the proposed new product, the currently approved product and the placebo.

Determine the antimicrobial properties of a proposed new product and an already approved product and a placebo (no drug). Study will be conducted using methods dictated by the FDA.

Most hemodialysis(HD) patients receive during HD intravenous iron compounds, which are composed of an iron core and a sugar polymer shell.~A small percentage of iron from the iron compound is released to the plasma, and may be associated with increased oxidative stress and protein oxidation. The study's hypothesis is that HD with large pore dialyzers may remove to the dialysate iron which is bound to potentially dialyzable ligands, after it's release from intravenous iron compound administered during hemodialysis.~Ligand-bound iron removal is also hypothesized to be affected by dialysate calcium and bicarbonate concentrations, which may affect iron-ligand binding.~Study Specific aims are:~To evaluate~Iron removal assessing dialysate iron levels.~Effect of iron removal and it's associated experimental conditions on patient status, assessing plasma AOPP levels and inflammation related parameters~Study include 3 parts~Comparing large to small pore dialyzers~(To achieve baseline uniform conditions, patients will be on uniform dialysate bicarbonate and calcium concentrations of 33 mEq/L and 3 mEq/L,respectively, using large pore dialyzers during this part, besides the 2 HD sessions evaluating low pore dialyzers)~and after few week break~Using large pore dialyzers to compare~Low to high dialysate bicarbonate concentration (using uniform dialysate calcium concentrations of 3 mEq/L)~and after few week break~Low to high dialysate calcium concentrations concentration (using uniform dialysate bicarbonate of 33 mEq/L)~In each part, patients will be first evaluated in HD without IV iron administration, which will serve as a control for evaluation after a week in HD with IV iron administration.~In each part, patients will be randomized to start either with one of the 2 experimental conditions, and after 1 week without evaluation will cross-over to the other experimental condition.~Patients may participate in 1,2 or the 3 parts of study depending on their will and condition.

The study's hypothesis is that HD with large pore dialyzers remove to the dialysate iron which is bound to potentially dialyzable ligands, after it's release from intravenous iron compound administered during hemodialysis.

To describe influenza vaccine coverage in children less than 18 years of age in practicing pediatricians' offices and family medicine physicians' offices and to examine correlations between in-office influenza vaccine coverage and the use of various tactics to increase vaccine coverage.

The purpose of this study is to describe flu vaccine coverage in children under 18 years of age and to examine correlations between in-office flu vaccine coverage and the use of various tactics to increase vaccine coverage.

Most critically ill patients receive sedative and analgesic drugs to attenuate discomfort and pain. The excessive use of sedatives and analgesics prolongs time on mechanical ventilation, the incidence of nosocomial pneumonia, time spent in the intensive care unit, and increases costs. Strategies to reduce the use of sedatives and analgesics may improve the outcome. Whereas undersedation is mostly easy to identify, oversedation with its associated problems is more difficult to recognize, but should be avoided. While stopping sedation daily helps to avoid gross oversedation, this is not always possible, e.g. due to unstable condition of the patient. Also, accumulation of sedatives and analgesics may occur rapidly, especially in patients with renal and/or liver dysfunction. Monitoring the depth of sedation is difficult and is currently based on clinical assessment and the use of clinical scoring systems. These scoring systems cannot be applied continuously, they are subjective and the level of consciousness can be altered when sedation is assessed.~Several methods based on the electroencephalogram have been tested to avoid these problems, but the results have been disappointing so far. A relatively new method of processed EEG is Entropy®. Entropy is a non-linear statistic parameter which describes the order of random repetitive signals. In patients it translates the anesthesia-induced calmer, more synchronized EEG into a single parameter. Spectral entropy can reproducibly indicate the hypnotic effects of propofol, thiopental and different anesthetic gases. The most popular method of processed EEG for assessment of sedation is the bispectral index (BIS-Index®). While BIS has been tested and validated for the use in the operation room with different anesthetics, data on its use in the ICU setting at less deep levels of sedation are controversial. The multiple concomitant medications and heterogeneity of underlying pathologies present a further challenge to the use of neuromonitoring in the ICU.~We have previously shown that the time-locked cortical response to standard external stimuli (long-latency auditory evoked potentials or event-related potentials; ERPs) can discriminate between clinically relevant light to moderate and deep sedation levels in healthy volunteers, when sedation is induced with a combination of propofol or midazolam with remifentanil.~We therefore hypothesized that ERPs may be used to monitor the depth of sedation in ICU patients as well. As the first step to test this hypothesis, we evaluated the use of ERPs to assess the level of sedation in patients undergoing elective major surgery and admitted to the ICU for short term postoperative mechanical ventilation.

Most critically ill patients receive sedative and analgesic drugs to attenuate discomfort and pain. The excessive use of sedatives and analgesics has undesirable effects for patients. Whereas undersedation is mostly easy to identify, oversedation with its associated problems is more difficult to recognize. Stopping sedation daily helps to avoid gross oversedation, but this is not always possible. Monitoring the depth of sedation is difficult and is currently based on clinical assessment and the use of clinical scoring systems. These scoring systems cannot be applied continuously, they are subjective and the level of consciousness can be altered when sedation is assessed.~Several methods based on the electroencephalogram have been tested to avoid these problems, but the results have been disappointing so far, so the BIS Monitor an dthe Entropy monitor.We have previously shown that the time-locked cortical response to standard external stimuli (long-latency auditory evoked potentials or event-related potentials; ERPs) can discriminate between clinically relevant light to moderate and deep sedation levels in healthy volunteers, when sedation is induced with a combination of propofol or midazolam with remifentanil.~We therefore hypothesized that ERPs may be used to monitor the depth of sedation in ICU patients as well. As the first step to test this hypothesis, we evaluated the use of ERPs to assess the level of sedation in patients undergoing elective major surgery and admitted to the ICU for short term postoperative mechanical ventilation.

Magnetic Resonance Imaging (MRI) has been utilized for 20 years as a clinical and research tool at SUNY Upstate Medical University. Currently, there are five (5) MR (1 low-field 0.2 Tesla, 3 high-field 1.5 Tesla and 1 3.0 Tesla) units in use on the university campus. During this time, new imaging sequences and hardware including smaller more powerful magnets and faster computers have been developed that assist in the diagnosis of many disease processes. MR Angiography, MR Spectroscopy, diffusion weighted imaging and a dedicated combination Neurovascular head and neck coil are just several of the many imaging sequences and specialized coils that have been developed over the last several years.~New imaging sequences and hardware including 4.0 and 7.0 Tesla magnets are currently undergoing development and testing at several universities in the United States and worldwide. As a consequence of the many new innovations in MR imaging we must periodically upgrade our existing MR units and on occasion replace one of our existing MR units or purchase a new MR unit. This will ensure that we have the most up to date MR equipment to provide state of the art diagnostic imaging capabilities at University Hospital. The new imaging sequences and/or hardware must be optimized for each MR unit to achieve the highest signal to noise (SNR) and contrast to noise (CNR) ratios in a reasonable scan time. This practice is routinely performed at every university and private hospital as well as outpatient imaging center when a new MR unit is installed and when an existing unit is upgraded.~Ultrasound imaging has been a component of the Radiology Department since 1975 and used as a clinical and research tool. Presently our machines include the GE's models: Logic E9, S8, Logic (, P5, P6, Logic Book, Phillips IU22, SonoSite Turbo (multiple units), Siemens Acuson (x3 units) and a Siemens X300.~There are updated ultrasound machines that allow color Doppler images and elastography acquisition ability. Upgrades for software and hardware are on an ongoing basis along with new applications and imaging protocols.

Magnetic Resonance Imaging (MRI) is a non-invasive diagnostic imaging technology that produces images of the body. This technology does not utilize radiation, as does Computed Tomography (CT) but relies on radio waves and a strong magnet to produce images.~The purpose of this study is to evaluate new commercially available MR imaging sequence and/or hardware that have been installed on an existing MR unit or to evaluate a new MR unit. The study also serves to familiarize the MR technical staff with how to operate the new equipment. The information obtained will be used to optimize new MR equipment that has been installed on the MR scanner~There are updated ultrasound machines that allow color Doppler images and elastography acquisition ability. Upgrades for software and hardware are on an ongoing basis along with new applications and imaging protocols.~There are updated ultrasound machines that allow color Doppler images and elastography acquisition ability. Upgrades for software and hardware are on an ongoing basis along with new applications and imaging protocols.~There are updated ultrasound machines that allow color Doppler images and elastography acquisition ability. Upgrades for software and hardware are on an ongoing basis along with new applications and imaging protocols

Sedation may be necessary in intensive care to facilitate diverse therapeutic interventions, but the use of sedative drugs may increase the risk of delirium and long-term cognitive impairment. Thus the implementation and monitoring of sedation remains difficult despite the use of sedation protocols and clinical sedation scores. Attempts to improve sedation monitoring through the use of the electroencephalogram (EEG) have been disappointing. Derived variables based on the unstimulated EEG fail to predict the response to external stimuli at the clinically most relevant light-to-moderate sedation levels, and the overlap between moderate and deep sedation levels is wide. We have demonstrated that long-latency auditory evoked potentials (ERPs)can be used to avoid deep levels of sedation in healthy volunteers during propofol sedation, independent of the concomitant administration of remifentanil. This approach has a potential clinical application for improved monitoring of sedation. Since the effects of different sedative drugs on the EEG may vary widely, the use of ERPs to monitor sedation needs to be evaluated with different sedative drugs. The alpha-2 agonist dexmedetomidine (dex) has been approved for short-term sedation in surgical intensive care unit (ICU) patients. Preliminary data suggest that the risk of delirium may be substantially reduced when dexmedetomidine is used to produce sedation. Since dexmedetomidine acts via different receptors and brain areas than do benzodiazepines and propofol, its impact on the brain electrophysiology may also be different. The assessment of dexmedetomidine's effects on the EEG and ERPs at various sedation levels has been limited in humans. We hypothesized that the combinations DEXMEDETOMIDINE/REMIFANTANIL (dex/remi) and MIDAZOLAM/REMIFENTANIL (mida/remi) would induce the same changes in EEG and long-latency ERPs during light-to-moderate levels of sedation in healthy subjects, despite the different quality of sedation that they provide. The opioid remifentanil was added because virtually all patients in the ICU have some level of pain and receive an opioid analgesic in combination with a sedative. 10 healthy subjects were assessed with both drug combinations (dex/remi and mida/remi), at least 7 days apart. The sequence of the drug combinations were randomized.

Sedation may be necessary in intensive care to facilitate diverse therapeutic interventions, but the use of sedative drugs may increase the risk of delirium and long-term cognitive impairment. Thus the implementation and monitoring of sedation remains difficult despite the use of sedation protocols and clinical sedation scores. Attempts to improve sedation monitoring through the use of the electroencephalogram(EEG) have been disappointing. Derived variables based on the unstimulated EEG fail to predict the response to external stimuli at the clinically most relevant light-to-moderate sedation levels, and the overlap between moderate and deep sedation levels is wide. We have demonstrated that long-latency auditory evoked potentials (ERPs)can be used to avoid deep levels of sedation in healthy volunteers during propofol sedation, independent of the concomitant administration of remifentanil. This approach has a potential clinical application for improved monitoring of sedation. Since the effects of different sedative drugs on the EEG may vary widely, the use of ERPs to monitor sedation needs to be evaluated with different sedative drugs. Therefore we will administer two widely used drug combinations (dexmedetomidine/remifentanil and midazolam/remifentanil) in healthy volunteers and record ERPS and processed EEG during clinical relevant sedation levels

The incidence of poor fetal growth and adverse maternal and infant birth outcomes is quite high in India, and several lines of evidence suggest that maternal nutritional status may be an important factor. We have previously performed extensive evaluations of poor fetal and infant outcomes in other settings, and found that maternal micronutrient supplementation (B vitamins including vitamin B12, plus vitamins C and E) in HIV positive Tanzanian mothers decreased the risk of low birthweight (<2500 g) by 44% (RR (95% CI) 0.56 (0.38-0.82)), severe preterm birth (<34 weeks of gestation) by 39% (RR 0.61 (0.38-0.96)), and small size for gestational age at birth by 43% (RR 0.57 (0.39-0.82)). In a prospective cohort study of 410 pregnant Indian women, we recently found a strong relationship between maternal serum vitamin B12 concentration and risk of infant intrauterine growth retardation (IUGR). Compared to women in the highest tertile of serum B12 concentration, women in the lowest tertile were significantly more likely to have IUGR infants, after controlling for maternal age, weight, education, and parity (OR (95% CI) 5.98 (1.72-20.74)). We now propose a randomized, double-blind trial among 300 pregnant Indian women in order to determine the effectiveness of vitamin B12 supplementation (50 µg daily) in improving maternal B12 status. Secondary aims for this exploratory trial include maternal hemoglobin, maternal weight gain during pregnancy and infant birthweight. All women will receive standard of prenatal obstetric care, including routine supplementation with iron and folate. The study will be a collaborative effort between the Division of Nutrition, St John's Research Institute, Bangalore, India, and the Department of Nutrition, Harvard School of Public Health, Boston, US.

This study is a randomized, double-blind trial among 300 pregnant Indian women in order to determine the effectiveness of vitamin B12 supplementation in improving maternal B12 status. Secondary aims for this trial include maternal hemoglobin, maternal weight gain during pregnancy and infant birthweight. All women will receive standard of prenatal obstetric care, including routine supplementation with iron and folate.

(IRB# Pro00005035)~The purpose of the study is to determine the role of nitric oxide (NO) in asthma and to characterize the symptoms associated with inhaled endotoxin in normal subjects. The effect of inhaled endotoxin on exhaled NO is determined in healthy African Americans, with and without NOS2 promoter polymorphisms. The protocol involves the use of NIH Clinical Center Reference Endotoxin which has been approved by the FDA under IND BB-IND-10035.~Background & significance: Asthma is a significant cause of morbidity and mortality for African Americans and asthma is increasing in prevalence. Both environmental and genetic factors contribute to the pathogenesis of asthma. In addition to allergens, environmental lipopolysaccharide (LPS) or endotoxin plays an important role in the chronic inflammation associated with asthma. There is convincing evidence that endotoxin exacerbates airflow obstruction and airway inflammation in allergic asthmatics. Endotoxin increases inducible nitric oxide synthase (NOS2) expression and nitric oxide (NO) production in vitro and in vivo in humans.~In asthma, NOS2 expression is upregulated in several cell types including bronchial epithelium, macrophages and other inflammatory cells. The increase in NOS2 expression is associated with increases in exhaled NO in individuals with asthma as compared to healthy individuals.~This prompted our search for NOS2 single nucleotide polymorphisms (SNPs) and the subsequent identification of three NOS2 promoter SNPs. Two of the SNPs are associated with increased systemic NO levels. Another SNP creates a predicted binding site for the human homolog of delta EF1, which is a transcriptional repressor and we predicted that this SNP would be associated with low NO levels. Importantly, the three NOS2 promoter SNPs are not linked, do not segregate together and are present primarily in individuals of African ancestry.~Design & procedures: The study of exhaled NO levels in individuals with asthma is confounded by the presence of cell types besides bronchial epithelium that produce NO, by differences in the severity of asthma and by the use of medications such as corticosteroids which alter exhaled NO levels. Therefore, in this protocol exhaled NO levels are measured in asymptomatic healthy African Americans.~Thirty individuals (10 individuals with each polymorphism) who are heterozygous for a NOS2 promoter SNPs and 10 individuals without these NOS2 promoter SNPs will be studied. The decision to study 10 individuals in each group was based on a power analysis (80% power, 0.05 alpha) using available data on NO levels in normal individuals following endotoxin challenge. Because basal NO levels in patients with asthma are approximately twice that of normal individuals, we decided that a two-fold difference in exhaled NO levels following endotoxin challenge represents a meaningful difference.~The general design of this study is to identify healthy nonasthmatic, nonatopic, never cigarette smokers with no history of airway reactivity, and subject them to a specific incremental challenge with inhaled LPS to determine the airway reactivity to inhaled endotoxin. Upon recruitment, each study subject will be scheduled for seven separate visits, with the option of 3 additional visits after each challenge. During the initial visit, each study participant will undergo a thorough clinical evaluation including 2 questionnaires, a physical examination, skin tests to assess the presence of atopy, full pulmonary function testing, a chest x-ray, an EKG, and a methacholine challenge test to assess airway hyperreactivity, exhaled nitric oxide and exhaled breath condensate samples to measure inflammatory mediators. During the challenge visits, each subject will undergo a specific incremental challenge with inhaled endotoxin or the vehicle (saline). The initial evaluation and the endotoxin inhalation challenge will be separated by a minimum of two weeks. A brief follow up visits will be scheduled to collect blood samples, exhaled gases 24, 48, 72hours and 7 days after endotoxin challenge and to obtain full pulmonary function testing with airway resistance performed at baseline. To avoid problems with diurnal variation in pulmonary function, all testing sessions will begin at 8:00 AM. All testing will be performed in the Rankin Duke Clinical Research Unit at Duke University. Serum pregnancy testing will be performed during the initial visit and the days of each endotoxin and saline inhalation challenge to exclude pregnant women from this study. Administration of endotoxin or saline will not occur until results of the pregnancy test have returned negative.~In addition to serum pregnancy testing, blood samples will be obtained to determine IgE levels (to determine whether subject has allergies; determined at visit 1 only), cotinine levels (a metabolite of nicotine and used to determine whether subject smokes; determined at visits 1, 2, 4 and 6), CRP and cytokine levels (markers of inflammation used to determine whether systemic responses to inhaled endotoxin occur; determined at visits 2, 3, 4, 5, 6 and 7), and RNA levels (to be analyzed using gene arrays and used to determine whether systemic responses to inhaled endotoxin occur; determined at visits 2, 3, 4, 5, 6 and 7). On visits 2, 4 and 6, CRP, cytokine and RNA levels will be determined three times, initially to establish baseline levels and 2 and 6 hours after endotoxin or saline challenge. On visits 3, 5 and 7, CRP, cytokine and RNA levels will be determined once. The URI questionnaire will be administered at the beginning of all visits to assess whether subjects have symptoms consistent with a URI or cold.~The Duke Investigational Pharmacy will prepare the inhaled solution of endotoxin according to a standard protocol which has been used successfully by other investigators, as well as in our own laboratory. Each subject will receive an initial dose of Saline Solution as a baseline. During the second visit, inhalations will contain increasing concentrations of endotoxin (Clinical Center Reference Endotoxin (CCRE), a lot of endotoxin prepared from the bacterial strain E. Coli O:113 and maintained by the Pharmaceutical Development Service, Warren Grant Magnuson Clinical Center, National Institutes of Health) according to the following schedule: 5,000 EU (endotoxin units); 10,000 EU; and 20,000 EU. During the higher dose challenge visit, inhalations will contain 40,000 EU and 80,000 EU of endotoxin. Following inhalation of each dose of endotoxin or each saline challenge, we will obtain several spirometric measures of airflow. Airflow will be assessed 1, 10, 20, and 30 minutes following each dose of inhaled LPS or saline. If the study subject's FEV1 is more than 80% of the baseline measurement, the inhalation challenge will continue and the next higher dose of endotoxin will be administered. During the control visit, saline control will be administered on three occasions. After each dose of inhaled endotoxin or saline, non-pulmonary adverse events will be assessed and graded. The protocol will conclude if any of the following criteria have been met: 1) subject does not wish to continue for any reason; 2) subject's FEV1 has decreased 20% from baseline saline inhalation; 3) total dose of 35,000 units (low dose challenge visit) or 120,000 units (high dose challenge visit) has been achieved; or 4) the subject experiences any adverse event rated as severe or any other adverse event deemed significant in the opinion of the investigator. Following completion of the inhaled endotoxin or saline challenge, pulmonary function studies, vital signs and symptom assessments will be performed to assess the safety of the inhaled endotoxin procedure (see attached IND protocol for details). We will also collect exhaled breath condensate samples to measure inflammatory mediators including leukotrienes and to control for the confounding effects of airway inflammation on exhaled NO levels. Exhaled breath condensate will be collected from subjects by having them breathe normally for approximately 10 minutes into an apparatus that traps condensation by cooling the exhaled breath. We will measure airway resistance at 1, 2, 6 and 24 hours after endotoxin or saline challenge. Measurement of spirometry, lung volumes, diffusing capacity will be repeated at 6 hours and 24 hours post challenge.~We will measure exhaled NO levels using an online chemiluminescent detector (Sievers 280i) prior to and 1, 2 and 6 hours after endotoxin or saline challenge. We will also measure exhaled NO levels 24 hours after exposure to endotoxin or saline.~Subjects will be requested to come for additional optional physiologic measurements at 48, 72 and 168 hours post challenge to gather data further in the time course. For the optional visits after each challenge, subjects will have vital signs measured, CRP and serum for other inflammatory markers drawn. Subjects will perform spirometry, lung volumes, diffusing capacity, exhaled NO levels, airway resistance, and complete a short questionnaire.~NOTE:~In a separate related IRB protocol prior to the above study:~In Phase 1, (IRB # Pro00005046) we will determine the effect of promoter polymorphisms in the gene for the NO producing enzyme, nitric oxide synthase (NOS2), on exhaled NO in healthy African Americans. Individuals consented during Phase 1 will be asked if they are willing to be contacted about future studies including those described in Phase 2 of this study. 30 individuals (10 individuals with each polymorphism) identified in Phase 1 who are heterozygous for a NOS2 promoter SNPs and 10 individuals without these NOS2 promoter SNPs will be studied.~Because SNPs in the TLR4 gene result in a lack of airway obstruction in response to endotoxin, we will genotype the 1000 DNA samples for the Asp299Gly and Thr399Ile TLR4 polymorphisms in Phase 1 and exclude these individuals from the studies proposed in Phase 2. Likewise, CD14 serves as a coreceptor for endotoxin and polymorphisms in the CD14 gene and promoter have been associated with asthma and responsiveness to endotoxin. Therefore, to control for this potential confounder in our analysis, we will also test whether polymorphisms in the CD14 gene and its promoter are associated with responsiveness to inhaled endotoxin.

The purpose of the study is to determine the role of nitric oxide (NO) in asthma and to characterize the symptoms associated with inhaled endotoxin (lipopolysaccharide [LPS]) in normal subjects. In this study, we will determine the effect of inhaled endotoxin on exhaled NO in healthy African Americans, with and without NOS2 promoter polymorphisms. The protocol described in this submission will involve the use of NIH Clinical Center Reference Endotoxin which has been approved by the FDA under IND BB-IND-10035.

Evaluation of hydration status during exercise and heat exposure.

Evaluation of hydration status during exercise and heat exposure.

This is an open-label, single dose, two-treatment, two-period, cross-over study to evaluate the pharmacokinetic profile and tolerability of galantamine oral solution and galantamine tablet. All patients are healthy male patients who are 18-45 years old with BWI (Body Weight Index) between 18-28 kg/m2. All patients must sign informed consent before being enrolled. 24 patients were randomized in the study. The duration of study is 9 days. All patients must stay at site unit for 12 hours after single oral administration otherwise patients could stay home but must return to site at specific date and time. The day before dosing day (baseline), patients were randomized to one of the two groups to be administered either 4mg galantamine oral solution (1ml) or galantamine tablet (1 tablet). After 7-day washout period, patients were crossed over to receive the other formulation. Pharmacokinetic observation will last to 32 hours after dosing. Plasma were collected at immediately before dosing and 0.25, 0.5, 0.75, 1.5, 2, 3, 4, 6, 8, 12, 24 and 32 hours after dosing to determine plasma concentration of galantamine. Safety and tolerance evaluation will last until Day 9. Safety evaluation include adverse events, vital signs, physical examination, electrocardiogram and laboratory tests. On study Day 1, patients will take either 4mg galantamine oral solution (1ml) or 4mg galantamine tablet (1 tablet). After 7-day washout period, on Day 8, patients will cross over to take the other formulation, the dosage and administration are the same.

The purpose of this open-label, single dose, two-treatment, two-period, cross-over study is to evaluate the pharmacokinetic profile and tolerability of galantamine oral solution and galantamine tablet.

This research study is about the significance of polyunsaturated fatty acids (PUFAs) for human development. Specifically, the study team will assess the effect of docosahexanoic acid (DHA) supplementation during pregnancy on infant growth and development through a randomized controlled intervention trial in Cuernavaca, Mexico. This is a collaborative effort between the Rollins School of Public Health, Emory University, the Instituto Nacional de Salud Publica (INSP) and the Instituto Mexicano del Seguro Social (IMSS), Cuernavaca, Mexico. Pregnant women attending the IMSS General Hospital I are recruited between 18-22 wks gestation and assigned randomly to receive either DHA (400 mg) or a placebo daily until delivery. The main study outcomes include a) birth outcomes: birth size, gestational age, cord blood levels of DHA and neurodevelopment b) maternal blood and breast milk DHA levels at 1 and 3 mo post-partum c) postnatal growth and development during the first 5 years of age and d) infant DHA status at 3, 12 and 18 mo. All data collection is carried out at the study headquarters (IMSS) except for home environment that is assessed during home visits. Physical growth (length, weight, and head circumference) and infant and child development (visual and auditory evoked potentials, visual attention, Bayley scales of infant development, McCarthy child development score, Hearts and Flowers stroop test, and other computerized child development tests) are measured at birth, 1, 3, 6, 9, 12, 18, 24, 36 months and at 4 and 5 years of age by trained workers. Data are also obtained on socioeconomic status, obstetric history, maternal diet, anthropometry and intelligence, quality of home environment and infant feeding practices. Data analysis will include group comparisons (intent-to-treat) after ensuring effectiveness of randomization, and structural equation modeling to examine the various pathways by which DHA supplementation during pregnancy affects child growth and development. The findings of this project will contribute significantly to our understanding of the functional consequences of DHA supplementation during pregnancy.

This research study research is about the significance of polyunsaturated fatty acids (PUFAs) for human development. Specifically, the study team will assess the effect of docosahexanoic acid (DHA) supplementation during pregnancy on infant growth and development through a randomized controlled intervention trial in Cuernavaca, Mexico. This is a collaborative effort between the Rollins School of Public Health, Emory University, the Instituto Nacional de Salud Publica (INSP) and the Instituto Mexicano del Seguro Social (IMSS), Cuernavaca, Mexico. Pregnant women attending the IMSS General Hospital I are recruited between 18-22 weeks gestation and assigned randomly to receive either DHA (400 mg) or a placebo daily until delivery. The main study outcomes include a) birth outcomes: birth size, gestational age, cord blood levels of DHA and neurodevelopment b) maternal blood and breast milk DHA levels at 1 and 3 months post-partum, c) postnatal growth and development during the first 5 years of age and d) infant DHA status at 3, 12 and 18 months.

Brittle nails, referring to nails that chip, peel, or split excessively, occur in up to 30% of women and 15% of men, with highest prevalence among the elderly. Treatment of brittle nails involves restoration and maintenance of a normal degree of nail plate hydration by minimizing exposure to dehydrating chemicals and by use of moisturizers, such as alpha-hydroxy acids. Retinoids are vitamin A analogs that play a role in skin cell differentiation and proliferation. Tazarotene is a topical receptor-selective synthetic retinoid that normalizes epidermal differentiation and reduces the influx of inflammatory cells into the skin. In this single-center, open-label trial, subjects applied tazarotene to the nails twice daily for 24 weeks. Signs and symptoms were rated by the investigators and subjects during treatment and 12 weeks after discontinuation.

The purpose of this study is to determine whether topical tazarotene (Tazorac), a receptor-selective synthetic retinoid that normalizes epidermal differentiation, ameliorates signs and symptoms of brittle nails.

This trial consists of two parts: a partially blinded dose-finding part followed by an open-label part with the recommended dose of TMC114/RTV. The dose-finding part of this trial consisted of a randomized controlled (standard of care), partially blinded, Phase II trial to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir. The pharmacokinetics of TMC114 are also assessed.Three hundred HIV-1 infected patients who were three-class-experienced and who were on a stable PI-containing regimen at screening for at least 8 weeks and who had plasma HIV-1 RNA > 1000 copies/mL were eligible. Three-class experience was defined as prior treatment with ³ 2 NRTIs for at least 3 months in total and ³ 1 NNRTI as part of a failing regimen. In addition, patients had to have received at least one PI for at least 3 months in the past and had to have at least 1 primary PI mutation (according to IAS definitions) at screening.As soon as all results to determine eligibility were available, and no later than 2 weeks prior to the baseline visit, the patients were randomized to one of 4 TMC114/RTV treatment groups or to a control group (standard of care). At baseline, patients changed to an investigator selected PI(s) regimen or TMC114/RTV plus optimized background regimen (OBR) consisting of NRTIs with or without T-20.In the dose-finding part of the trial, the primary objective of the trial was to evaluate the dose-response relationship in antiviral activity between the TMC114 /RTV treatment groups at 24 weeks. The recommended dose has been selected based on two joint interim analyses of this trial and of a similar trial (TMC114-C202, conducted in the United States of America, Puerto Rico, and Argentina) including approximately 150 patients in each of the two dose-finding trials (TMC114-C202 + TMC114-C213) who reached Weeks 16 and 24 or dropped out earlier. The Week 24 interim analysis included a total of 497 patients, of whom 329 had reached Week 24 or discontinued earlier. Based on the results of these two joint interim analyses, TMC114/RTV 600/100 mg b.i.d. was selected as the recommended dose for the open-label part of this trial and for future trials in treatment-experienced HIV-1 infected patients. The recommended dose of TMC114/RTV was not communicated to the investigators until the data cut-off date for the primary efficacy analysis of the two dose-finding trials was reached.The primary efficacy analysis was performed when approximately 300 patients in this trial reached 24 weeks of treatment or discontinued earlier (i.e., the primary endpoint, which was reached on 1 February 2005; A total of 318 patients were included in the analysis of whom 301 reached Week 24 or discontinued earlier). In this primary efficacy analysis, all TMC114 groups were compared to the control group by means of the confirmed virologic response at Week 24, defined as a drop in viral load of at least 1 log10 versus baseline. This primary efficacy analysis confirmed that TMC114/RTV 600/100 mg b.i.d. is the recommended dose for treatment-experienced HIV-1 infected patients.After the primary endpoint of the trial was reached (1 February 2005), and after approval of the related protocol amendment by the relevant IEC/IRB and authorities, the patients in the TMC114/RTV groups were instructed to switch to the recommended dose of TMC114/RTV (600/100 mg b.i.d.) in the open-label part of the trial.In addition, long term safety, tolerability and the durability of antiviral activity of TMC114/RTV over 144 weeks in 3-class-experienced HIV-1 infected patients will be evaluated. The trial includes a screening period of a maximum of 6 weeks, and a 144-week treatment period followed by a 4-week follow-up period. The maximum duration of the trial will be 154 weeks.Tibotec will provide follow-up treatment with TMC114/RTV for all patients who continue to benefit from treatment with TMC114/RTV. TMC114 will be provided until the drug is commercially available or until its development is discontinued.The patient will remain on the study until he/she no longer benefits from TMC114/RTV, as judged by the investigator, or he/she meets one of the withdrawal criteria. Dose-finding part of the trial: 400 mg/100 mg q.d. TMC114/RTV or 800 mg/100 mg q.d. TMC114/RTV or 400 mg/100 mg b.i.d. TMC114/RTV or 600 mg/100 mg b.i.d. TMC114/RTV. Open-label part of the trial: 600 mg/100 mg b.i.d. TMC114/RTV. Total treatment duration of 144 weeks.

The purpose of this study is to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir

Transporting acute-care patients who require mechanical ventilation within a hospital can be fraught with hazards. Prior studies have revealed a high level of transport-associated complications including episodes of hypertension, hypoxemia, respiratory arrest, and death (1). In many institutions, the preferred method of transporting intubated patients is to use manual ventilation with a resuscitator bag, an approach that fully occupies one member of the transport team. Using a transport ventilator involves taking an intubated patient who has been placed on one ventilator and switching the patient to the transport ventilator; until now, transport ventilators had not been designed to match the capabilities of the more robustly engineered critical care ventilators.~The use of noninvasive ventilation (NIV) to treat patients with COPD exacerbations and other forms of respiratory failure has increased because of its demonstrated efficacy in reducing the need for intubation as well as morbidity and mortality (2). None of the ventilators usually used for noninvasive ventilation was designed for in-patient transport.~Currently, the standard of care in this institution is to transport intubated patients receiving mechanical ventilation by using a manual resuscitation bag and to transport patients receiving NIV by placing the patient on oxygen therapy without ventilatory support.~The VersaMed iVent ventilator was designed to treat respiratory failure in the acute care setting. The device is suitable for patients who are intubated as well as for patients receiving noninvasive ventilation, has a backup battery so that it can function during transport, and has been approved by the FDA for invasive and noninvasive mechanical ventilation. This device permits continuity of mechanical ventilation virtually regardless of patient status.~We propose to evaluate the utility of the VersaMed iVent ventilator in the acute care setting, hypothesizing that, in comparison to the standard approach, the use of the VersaMed will facilitate transport, reduce transport-associated complications, and provide equivalent ventilatory support and transport-success rates for both intubated patients and patients receiving NIV.~References~Braman SS, Dunn SM, Amico CA, Millman RP. Complications of intrahospital transport in critically ill patients. Ann Intern Med 1987; 107:469-73.~Mehta S, Hill NS. Noninvasive ventilation-state of the art. Am J Respir Crit Care Med 2001; Feb; 163(2):540-77.

The purpose of this study is to evaluate the use of the VersaMed iVent ventilator in the acute care setting, hypothesizing that, in comparison to the standard approach, the use of the VersaMed will facilitate transport and reduce transport-associated complications while providing equivalent ventilatory support and transport success rates for both intubated patients and patients receiving noninvasive ventilation.

This was a multicentre, single-arm, open-label study. The objective of this phase IV study was to document the experience of women with the transdermal contraceptive patch (a weekly contraceptive patch delivering 150 mg norelgestromin/20 mg ethinyl estradiol daily) over a period of 9 cycles, compared to their previous contraceptive method. An open-label, multicentre, descriptive cohort study of 392 women requiring contraception were enrolled to receive the patch for nine cycles. A single treatment cycle consisted of three consecutive 7-day patch applications followed by one patch-free week. At the final visit, overall satisfaction and preference for the patch was rated compared to the previous contraceptive method.) The primary outcomes were treatment preference and overall satisfaction. Compliance, contraceptive efficacy, adhesion, and safety measures were secondary outcomes. Study participants were scheduled to receive the contraceptive patch for up to nine consecutive treatment cycles. Participants attended the clinic for 3 study visits: baseline/screening, Day 28 of Cycle 3 and Day 28 of Cycle 9 (or at early termination). A telephone interview was conducted on Day 28 of Cycle 6. Approximately 400 women were to be enrolled into the study and receive the transdermal contraceptive patch. Patients were recruited using ethics approved advertisements, in addition to investigators approaching patients presenting for routine well-woman checks. Participants who met all of the eligibility criteria were instructed to apply the first patch on the first day of their next menses (or 13 weeks following the last medroxyprogesterone acetate injection) and to wear this patch for seven days. They were then instructed to apply a new patch for weeks 2 and 3, and then be patch-free for week 4. Applying a new patch on the day after week 4 ended started a new cycle. All patches were to be applied/changed on the same day of the week and at approximately the same time of day. Only one patch was to be worn at a time. Patches could be applied to the buttocks, abdomen, upper outer arm, or upper torso (excluding breasts) and participants were instructed to apply new patches to a different site. Patches were to adhere on their own; no supplemental tape or adhesive was permitted. If a patch partially detached, participants could reapply it; however, patches that completely detached were to be replaced immediately and the replacement patch would be worn for the remainder of that week. Eligible patients were instructed to apply the 1st patch on the first day of their next menses (or 13 weeks following last medroxyprogesterone acetate injection) and to wear this patch for 7days. They were then instructed to apply a new patch for weeks 2 and 3, and then be patch-free for week 4. Applying a new patch on the day after week 4 ended started a new cycle. All patches were to be applied/changed on the same day of the week and at approximately the same time of day.

The purpose of this study is to document the experience of transdermal contraceptive patch over a period of 9 cycles, compared to their previous contraceptive method.

Controlled, randomized, split-face study in which subjects receive JUVÉDERM™ Injectable Gel with Lidocaine (Ultra or Ultra Plus) in one nasolabial fold and JUVÉDERM™ Injectable Gel without Lidocaine (Ultra or Ultra Plus) in the other nasolabial fold. The investigator determines whether the subject receives JUVÉDERM™ Ultra or Ultra Plus per the level of correction desired; the lidocaine assignment is randomized.

Safety and effectiveness of JUVÉDERM™ Injectable Gel with Lidocaine compared to JUVÉDERM™ without Lidocaine for procedural pain in the treatment of nasolabial folds.

This was a Phase III, randomized, double blind, placebo controlled, multicenter, repeat dose study of the safety and efficacy of 2 dose levels of Acurox™ Tablets versus placebo for the treatment of moderate to severe postoperative pain following bunionectomy surgery.~Patients underwent a primary unilateral first metatarsal bunionectomy with or without ipsilateral hammer toe repair during standardized local anesthesia with intravenous (IV) sedation. Eligible patients who reported moderate or severe pain within 6 hours after surgery entered the Treatment Phase and were randomized to 1 of 3 double blind treatments: placebo tablets or 1 of 2 dose levels of Acurox™ Tablets (ocyxcodone HCl/niacin). The Treatment Phase continued with study medication every 6 hours (irrespective of rescue medication use) for 48 hours (8 doses of study medication). Toradol (ketorolac tromethamine) was available as a rescue medication upon request.

The purpose of this study is to determine whether oxycodone HCl and niacin are effective in the treatment of pain following bunionectomy surgery.

Acute respiratory distress syndrome (ARDS) is a pulmonary disease process that affects post-surgical patients in the intensive care unit and leads to significant patient morbidity and mortality and hospital cost. Extensive research has been conducted in the diagnosis and treatment of ARDS. To date, however, very little research examining the effect of the operative course on the development of ARDS has been reported. By examining the intraoperative anesthetic characteristics of patients who developed ARDS postoperatively, we hope to identify variables which have a positive or negative association on the development of ARDS. Once identified, the variables can be confirmed by future studies and encourage change in clinical care to decrease the occurrence of ARDS in surgical patients.

By examining the intraoperative anesthetic characteristics of patients who developed ARDS postoperatively, we hope to identify variables which have a positive or negative association on the development of ARDS.

This Phase IV, randomized, double-blinded study in volunteer subjects to evaluate the tolerability, safety, and flow rates of different solutions subcutaneously (SC) infused and preceded by human recombinant hyaluronidase (hylenex) 150 units. The study will be conducted in two sequential stages.~In Stage 1, the comparison will be NS solution to LR solution. Each subject will receive simultaneous SC infusions of 500 mL (from a 500 mL bag) of solution in each anterior thigh, consisting of NS in one thigh and LR in the other thigh. The thighs (left vs. right) to receive NS and LR will be randomized and double blinded. Immediately prior to the infusions, each thigh will have 150 units of hylenex simultaneously injected.~Tolerability will be assessed based on the subject's self-assessment of discomfort on a visual analog scale (VAS). Safety will be assessed by physical examination targeted at infusion sites, vital signs, and adverse events. The amount of fluid infused will be assessed by weighing the infusion bag, fluid and tubing at designated time points, and allowing the determination of flow rate.~Stage 2 will be conducted only if the observed Stage 1 VAS mean maximum pain score is at least 25 mm higher for one solution compared to the other. Stage 2 will evaluate the tolerability, safety, and flow rates of subcutaneously infused NS solution and buffered NS solution.

Randomized, double-blinded study that will evaluate the tolerability, safety, and flow rates of different solutions subcutaneously (SC) infused and preceded by human recombinant hyaluronidase (hylenex) 150 units.~In Stage 1, the comparison will be Normal Saline (NS) solution to Lactated Ringer's (LR) solution. Each subject will receive 500 milliliters (mL) of solution, consisting of NS in one thigh and LR in the other thigh. Immediately prior to the infusions, each thigh will have 150 units of hylenex.~In Stage 2, the comparison will be NS solution and buffered NS solution.

Clinicians use lidocaine intravenously in a fashion that suggests that it might have analgesic effects. Therefore, we test the hypothesis that lidocaine reduces pain intensity in response to experimental pain.

The purpose of this study is to study if lidocaine, given intravenously, reduces pain.

This project will study whether reminder prompts increase Pre-Admission Medication List (PAML) Builder application feature utilization. PAML Builder is an application designed and maintained by Partners Information Systems that assists clinicians in medication reconciliation - a process important for patient safety and quality of care. We have determined that several potentially helpful features of the application are not being utilized as frequently as had been expected. These features include:~copying the pre-admission medication list (PAML) to the clipboard~viewing the detailed audit trail of all changes made to the PAML~sorting the list of medications obtained from other electronic sources by therapeutic class.~Reminder prompts (sometimes referred to as Tip of the Day) have been employed to increase user awareness of underutilized application features. However, anecdotally some users find them unhelpful and potentially irritating. It is therefore important to determine whether reminder prompts accomplish the stated task of increasing application feature utilization. This project will compare PAML Builder application feature utilization before and after a pilot rollout of reminder prompts to determine whether they should be implemented permanently.

This project will study whether reminder prompts increase PAML Builder application feature utilization.

Renal transplantation is the most common and successful type of organ transplantation. Induction therapy with antibody plus the maintenance immunosuppressive agents have greatly improved graft survival in renal transplantation. Since mesenchymal stem cells(MSCs)have been used successfully to treat graft versus host disease and show immune modulation function both in vitro and in vivo and may help in repairing damaged tissue(s), we evaluate autologous MSCs as an alternative for antibody induction therapy. Moreover, we examine if MSCs could improve the recovery of early function in transplanted kidney.

The goal of this study is to evaluate autologous MSCs as an alternative for antibody induction therapy in renal transplantation.

Craniofacial reconstructive surgery involves a surgical approach to the craniofacial region to repair cranial vault and facial deformities. These procedures are undertaken in young children to improve appearance, prevent functional disturbances, and enhance psychosocial development. The surgery is extensive, often requiring wide scalp dissections and multiple osteotomies and has been associated with significant morbidity. Reported complications include intra-operative cardiac arrest, massive blood loss, intraoperative tracheal extubation, venous air embolism, hypotension, coagulopathy, bradycardia, postoperative seizures, surgical site infections, facial swelling, and unplanned postoperative mechanical ventilation. The most severe and commonly seen problems are associated with the rate and extent of blood loss. Studies report estimated blood loss to average between 60% and 100% of the patient's estimated blood volume, with a range of 20-500%.(Hildebrandt et al 2007) The accurate and timely estimation of blood loss is very difficult and results in imprecise quantitative and qualitative replacement. Clinically important hypotension, metabolic acidosis, anemia, polycythemia, dilutional coagulopathy, cardiac arrest, and death are all related to blood loss. The creation of this prospective observational registry will provide a means to describe the incidence of these and other clinically important perioperative problems.

Craniofacial reconstruction procedures are undertaken in young children to improve appearance, prevent functional disturbances, and enhance psychosocial development. These procedures involve wide scalp dissections and multiple osteotomies and have been associated with significant morbidity. The most commonly seen perioperative complications are associated with the rate and extent of blood loss. This prospective observational registry will be a research tool which will provide a means to evaluate perioperative management of these children at CHOP.

Morsellized compacted bone allograft can be used for revision arthroplasty of the hip. Treating the graft locally with an antiresorptive substance such as a bisphosphonate has decreased the graft resorption in animal studies and led to a remained bone density in a human series of 16 patients. In the present study we investigate if this increased bone density of the graft also causes a decreased micromotion of the implant relative the femur. 36 patients are planned to participate in a 1:1 randomized and prospective study comparing the bisphosphonate Clodronate to saline. Primary outcome will be micromotion over the first year but also secondary parameters such as late micromotion (between 12 and 24 months), re-loosening subjective outcome and safety.~We hypothesize that rinsing the graft in a bisphosphonate solution prevents its resorption and therefore may reduce the risk of mechanical failure. Patients are followed with radiograms, RSA (radiostereography) preop, postop, at 6 weeks, at 12 and 24 months and subjective months and subjective parameters including Womac and SF 12. The treatment is simple, cheap and appears virtually risk-free.

The primary focus of this study is to investigate whether increased bone density of the graft in revision arthroplasty of the hip can cause a decreased micromotion of the implant relative to the femur.

Purpose: to evaluate the effect of a brief computer program to prevent alcohol misuse for patients consulting in an emergency department and screened for alcohol misuse.~Design: A randomized controlled trial with patients blinded of study hypotheses. Randomization will be stratified on centers and the sex~Interventions:~Patients randomized in the experimental group will participate in an interactive computer program with video, questionnaires and information related to alcohol misuse. They will also be contacted by phone at 1 month and 3 months to reinforce the effect of the intervention.~Patients randomized in the control group will participate in an interactive computer program with questionnaires and information related to healthy diet. They will also be contacted by phone at 1 month and 3 months to reinforce the effect of the intervention.~Participants: all patients consulting in an emergency department will be screened regarding their alcohol consumption and misuse. All patients screened as having alcohol misuse will be invited to participate in the trial.~Outcomes: the main outcome is the declared alcohol consumption at 12 months. Patients will be evaluated by phone at 3, 6 and 12 months by an independent outcome assessor.~Analyses: An intention to treat analyses will be performed Number of patients: 600 patients will be included Number of centers:3 centres (university hospital) will participate

The purpose of this study is to evaluate the effect of a brief computer program to prevent alcohol misuse for patients consulting in an emergency department and screened for alcohol misuse.

The purpose of this study is to compare the bioequivalence of a test formulation of zolpidem tartrate tablets to an equivalent oral dose of the commercially available Ambien® (zolpidem tartrate tablets)in adult subjects under fed conditions.~Thirty-eight healthy, non-smoking, non-obese male and female volunteers at least 18 years of age will be randomly assigned in a crossover fashion to receive each of two zolpidem tartrate dosing regimens in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, following an overnight fast of at least 10 hours and a standardized, high fat breakfast, subjects will receive either a single oral dose of the test formulation, zolpidem tartrate (1 x 10 mg tablet) or a single oral dose of the reference formulation, Ambien® (1 x 10 mg tablet). After a 7 day washout period, on the morning of Day 8 following an overnight fast of at least 10 hours and a standardized, high fat breakfast, subjects will receive the alternate regimen. Blood samples will be drawn from all participants before dosing and for 12 hours post dose at times sufficient to adequately define the pharmacokinetics of zolpidem tartrate. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drugs and/or procedures. Blood pressure and pulse rate will be obtained prior to dosing and at 0.5, 1, 2, 4 and 12 hours post-dose. All adverse events whether elicited by query, spontaneously reported or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

The purpose of this study is to compare the bioequivalence of a test formulation of zolpidem tartrate tablets to an equivalent oral dose of the commercially available Ambien® (zolpidem tartrate tablets)in adult subjects under fed conditions.

This is a bioequivalence study designed to compare three solid states of ARQ 197 in normal healthy volunteers using a randomized crossover design.~The primary objective is to obtain pharmacokinetic data to assess bioequivalence among three solid states of ARQ 197: amorphous, crystalline polymorph A and crystalline polymorph B.

This is a bioequivalence study designed to compare three solid states of ARQ 197 in normal healthy volunteers using a randomized crossover design.