Transforming health care and outcomes for children with rare diseases is difficult within the current health care system. There is great variation in care delivery, inadequate and slow application of existing evidence, and ineffective use of available data to generate new knowledge. Individual care centers have inadequate numbers of patients for robust learning and improvement. In order to redesign the system, changes must take place at multiple levels, including the patient and family, clinician, practice and the network. The purpose of this project is to design, develop, and test further refinements to an improvement and research network focused on HLHS, the most severe congenital heart defect, and to use a registry to simultaneously improve clinical care, redesign care delivery systems and to conduct quality improvement, health services, outcomes, and comparative effectiveness research. The purpose of this initiative, specifically, is to improve care and outcomes for infants with HLHS by: 1) expanding the established NPC-QIC national registry to gather clinical care process, outcome, and developmental data on infants with HLHS between diagnosis and 12 months of age, 2) improving implementation of consensus standards, tested by teams, into everyday practice across pediatric cardiology centers, and 3) engaging parents as partners in improving care and outcomes. We utilize a quality improvement methodology, known as the adapted learning collaborative model, which expedites the implementation of tools and strategies that facilitate changes such as systematic care coordination, cardiovascular monitoring, and nutritional monitoring into every day practice. The NPC-QIC registry is used to document the impact of these changes on various care processes and outcomes (e.g., mortality rate, readmissions, and weight gain).

This study is being conducted to assess safety and efficacy of bone marrow transplant in severe and less severely affected children. In this study, we will transplant bone marrow or cord blood from a HLA-matched brother or sister instead of the currently more common method with a HLA-identical sibling donor. This is a multicenter, single arm trial for patients between 2 and 10 years of age who have less severe HbSS or sickle beta zero thalassemia. Patient must have an HLA identical sibling donor who is less than 10 years old and who does not have HbSS, SC or sickle beta zero thalassemia.

We recently published results from a NIDA-funded study of a brief behavioral treatment that was designed to reduce the troublesome cravings that smokers encounter when they attempt to quit smoking. This intervention was based on a growing body of neuroscience studies showing that memories for prior learning can be retrieved by the presentation of cues involved in that learning. Once retrieved, the memories enter into a brief period of vulnerability, during which they can be modified, but after which they are reconsolidated (restabilized) back into long-term storage. The treatment potential of this phenomenon was initially demonstrated in a Science report in which inpatient heroin addicts were briefly exposed to cues associated with heroin use in order to prompt the heroin use memories into a vulnerable state. Once the memories were in this state, the heroin addicts received extinction training consisting of protracted exposure to heroin associated cues. It was argued that extinction would change the memories such that the cues would no longer be associated with heroin administration and reward. Remarkably, after just two sessions of retrieval-extinction training (RET), the investigators found that craving in response to heroin cues was substantially reduced for up to 6-months post-treatment. This effect was observed relative to a control group that received retrieval involving non-heroin cues, followed by extinction. These impressive initial findings led us to replicate and extend the study in cigarette smokers. In our study, one group of smokers received two sessions of RET with smoking cues whereas a control group received the same training except that retrieval consisted of brief exposure to neutral, smoking-unrelated cues. Craving and other reactions to familiar and novel smoking cues were assessed in test sessions performed 24-hrs, 2-weeks and 1-month after intervention; smoking behavior was also assessed over 1-month follow-up. Remarkably, at 1-month follow-up, craving to both familiar and novel smoking cues was significantly lower in the group receiving R-E training vs. control. Even more striking was the 25% reduction in the number of cigarettes smoked per day in the RET group vs. control. [Also of significance was suggestive evidence that, relative to control participants, more participants in the RET group achieved a 60% reduction in smoking (from pretreatment levels)]. The proposed project will replicate and extend these findings by 1) increasing the dose of intervention so as to bolster the observed treatment effects, 2) employing brain imaging methods to identify patterns of brain activity uniquely associated with the intervention and potentially predictive of treatment outcome, 3) adding a control group that will enhance understanding of the effects of RET, and 4) extending follow-up period to more completely document the long-term effects of RET. Positive findings from this study could lead to the development of a brief, effective behavioral intervention to reduce the burden levied against society by smoking. Importantly, this intervention could be easily adapted to treat other forms of addiction and co-occurring anxiety disorders, such as PTSD.

This is an open-label study designed to investigate the feasibility and tolerability of a novel TMS treatment protocol to treat depression in women with post-partum depression. It is known that TMS can effectively treat depression. The FDA approved protocol lasts 6 weeks and is not feasible for many women with post-partum depression. We are investigating a 6 day treatment for depression which may be more acceptable for this population. We further hope to characterize the anti-depressant effect and durability of this protocol in order to design a larger trial.

This study is for patients that have been diagnosed with High Risk B-Lymphoblastic Leukemia (HR B-ALL). The investigational drug in this study is Ruxolitinib. The purpose of this study is to find out if the study drug, ruxolitinib, in combination with standard HR B-ALL treatment is safe and effective in children, adolescents, and young adults with HR B-ALL. Participants can expect to be in this study for the treatment period of approximately 26 months (females) or 38 months (males) plus the post-treatment follow-up. Subjects are considered on study during the post-treatment follow-up period until the subject is deceased, lost to follow-up, or until the study is completed. Subjects in this study will be followed until all enrolled subjects have been followed for 3 years from Day 1 or are deceased or lost to follow-up.

The purpose of this study is to determine if the medication lofexidine, taken together with buprenorphine or methadone, is more effective at reducing opioid craving, use and stress response than buprenorphine or methadone alone, and to see if this effect is different for men and women. Participants are randomly assigned to add either lofexidine or placebo to their buprenorphine or methadone treatment for five weeks. They return at the end of five weeks to participate in an opioid imagery task and stress task. Throughout the study, participants complete "CREMA" sessions (Cue Reactivity Ecologic Momentary Assessment) using an iPhone app three times a day. These sessions include looking at stressful and neutral pictures and rating stress and craving.

Pain control after tonsillectomy is imperative but often difficult. Current post-operative pain medication regimens include opioid analgesics and are often still inadequate. Though not standard of care, it is our practice to prescribe a single dose of oral steroid medication on the third day after surgery, when pain and swelling are at their peak, in order to assist with pain control and reduce opioid consumption. Though this practice has a rational theoretical basis, there is no prospective data supporting or discounting it. We aim to compare pain control, opioid consumption, and complication rates in children receiving post-operative steroids versus those who do not.

The study team is recruiting 20 adults with spasticity due to chronic stroke and 20 adults with no neurological injuries for a 4 day study over 1 week. In people with chronic stroke, one of the most common and disabling problems is spasticity (increased muscle tone or muscle stiffness). The purpose of this research study is to examine effects of dry needling on the nervous system (pathways between the muscle, spinal cord, and brain) in people with spasticity due to chronic stroke. Dry needling is a procedure in which a thin, stainless steel needle is inserted into your skin to produce a muscle twitch response. It is intended to release a knot in your muscle and relieve pain.

The total study duration is 4 visits over one week. The first visit will take about 1.5 hours, during which the study team will determine the best electrode placement and create a removeable cast of your arm or leg to aid in placing electrodes in the next visits. The second visit will take about 3 hours, during which dry needling will take place, and the fourth and fifth visits will take about 1.5 hour. During all visits you will be asked to participate in examinations of reflexes (muscle responses to non-invasive nerve stimulation) and arm/leg function.

This study is for patients that have been diagnosed with Non-Small Cell Lung Cancer (NSCLC).The investigational drug used in this study is CLN-081.

This study has 3 parts; Phase 1 Dose Escalation, Phase 1 Dose Expansion, and Phase 2a Dose Expansion:
-Phase 1 Dose Escalation: The main aim of this part of the study is to find a maximum tolerated dose for CLN-081. This will be done by slowly increasing the dose given to each participant or to small groups of participants until certain adverse effects are seen. All participants will be closely monitored by the study doctor and team. When the maximum tolerated dose has been found, it will be used in the subsequent parts of the study.
-Phase 1 Dose Expansion: In this part of the study more participants will receive the maximum tolerated dose to confirm the safety of this dose of the study medicine and to explore different dosing schedules, for example, taking the study medicine once a day versus twice a day.
-Phase 2a Dose Expansion: The main aim of this part of the study will be to see how well the study medicine works in reducing tumor size.

Participants can expect to be on this study for about 3 years.

The main objective of this study is to analyze sputum collected from the residue remaining from bronchoalveolar lavage (BAL) procedures to compare the cellular characteristics of BAL samples to those of sputum samples collected from the acapella® airway assist device. We intend to enroll volunteers who are being evaluated by an MUSC pulmonologist as part of their standard medical care. The Control Sputum sample will be collected by volunteers at home over a three day period using an acapella® airway assist device. The cellular profiles of the BAL and sputum samples will be analyzed by flow cytometry. Active participation in this study is expected to last less than one month and will be complete once a sample is obtained from the BAL procedure.