Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation.

BACKGROUND: When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR. METHODS: The Clinical Islet Transplantation consortium 01 study was a phase II, multicenter, open label, active control, randomized study. Twenty-four subjects were randomized to peritransplant intraportal and systemic treatment with either LMW-DS or heparin, targeting an activated partial thromboplastin time of 150 ± 10 seconds and 50 ± 5 seconds, respectively. C-peptide response was measured with a mixed meal tolerance test at 75 and 365 days after transplant. RESULTS: Low molecular dextran sulfate was safe and well tolerated with similar observed adverse events (mostly attributed to immunosuppression) as in the heparin arm. There was no difference in the primary endpoint (stimulated C-peptide 75 ± 5 days after the first transplant) between the 2 arms (1.33 ± 1.10 versus 1.56 ± 1.36 ng/mL, P = 0.66). Insulin requirement, metabolic parameters, Clarke and HYPO score, quality of life, and safety were similar between the 2 treatments groups. CONCLUSIONS: Even with low dosing, LMW-DS showed similar efficacy in preventing IBMIR to promote islet engraftment when compared to "state-of-the art" treatment with heparin. Furthermore, no substantial differences in the efficacy and safety endpoints were detected, providing important information for future studies with more optimal dosing of LMW-DS for the prevention of IBMIR in islet transplantation.

Body Image and Quality of Life and Brace Wear Adherence in Females With Adolescent Idiopathic Scoliosis.

BACKGROUND: Clinical evidence regarding the ability of braces to decrease the risk of curve progression to surgical threshold in patients with adolescent idiopathic scoliosis (AIS) continues to strengthen. Unfortunately, there is still a great deal of uncertainty regarding the impact of brace wear on psychosocial well-being or the impact of psychological well-being on brace wear adherence. The purpose of this study is to evaluate psychosocial well-being, in particular body image and quality of life (QOL), and brace wear adherence in female AIS patients undergoing brace treatment. METHODS: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) was a multicenter, controlled trial using randomized and preference assignments into an observation or brace treatment group. BrAIST patients were skeletally immature adolescents diagnosed with AIS having moderate curve sizes (20 to 40 degrees). Patients in the bracing group were instructed to wear a thoracolumbosacral orthosis, at least 18 h/d. Scores on the Spinal Appearance Questionnaire and the PedsQL4.0 Generic Scales from 167 female BrAIST patients who were randomized to brace treatment (n=58) and patients who chose brace treatment (n=109) were analyzed. RESULTS: At baseline and at 12 months, no differences were found between the least-adherent brace wear group (<6 h/d) and most-adherent brace wear group (≥12 h/d) patients in terms of major curve, body image, and QOL. In the most-adherent group, poorer body image scores were significantly correlated with poorer QOL scores at baseline, at 6 months, and at 12 months but not at 18 months. In general, body image scores and QOL scores were not significantly correlated in the least-adherent group. When comparing patients that had a ≥6 degree increase of their major curve between baseline and 12 months to patients that did not, there were no significant differences in body image or QOL scores. CONCLUSIONS: For females adolescents with AIS, body image and QOL do not have a significant impact on brace wear adherence and are subsequently not significantly impacted by brace wear. LEVEL OF EVIDENCE: Level II-therapeutic (prospective comparative study).

An exploration of information exchange by adolescents and parents participating in adolescent idiopathic scoliosis online support groups.

BACKGROUND: Research indicates that healthcare providers frequently fail to adequately address patients' health information needs. Therefore, it is not surprising that patients or parents of a sick child are seeking health information on the internet, in particular in online support groups (OSGs). In order to improve our understanding of the unmet health information needs of families dealing with adolescent idiopathic scoliosis (AIS), this study assessed and compared the types of information that adolescents and parents are seeking in OSGs. METHODS: This study used two publicly accessible AIS-related OSGs on the National Scoliosis Foundation (NSF) website that targeted those who are receiving brace treatment and those under observation without treatment. Information exchanges were coded as providing or seeking information. Types of information being exchanged were categorized into several AIS-specific and brace-specific categories. Through a review of over 8,000 messages, 305 adolescents with AIS and 300 parents of a child with AIS were identified and categorized based on stage of illness/treatment. One message from each individual was randomly selected and coded for analysis. RESULTS: There were significantly more (p < 0.001) parents that had a recently diagnosed child compared to recently diagnosed adolescents participating in the AIS-related OSGs, whereas there were significantly more (p = 0.004) adolescents that experienced brace treatment compared to parents of a child that experienced brace treatment. The most frequent information exchanged by adolescents and parents was AIS-related concerns regarding causes, diagnosis, and progression of the condition. However, compared to adolescents, parents exchanged this AIS-related information significantly more (p < .001) in their posts. Finally, compared to parents, adolescents exchanged significantly more information about appearance-related concerns regarding both AIS-related deformity (p < 0.002) and wearing a brace (p < 0.001). CONCLUSION: Families dealing with AIS are participating in OSGs to exchange information, in particular information related to the condition and to treatment. This study found similarities and differences regarding how information was exchanged (providing or seeking) and regarding frequency and types of information exchanged. Knowledge of these similarities and differences may be useful for improving health communication in the healthcare setting, at home, and for development and improvement of AIS-related website support.

Body Image and Quality-of-Life in Untreated Versus Brace-Treated Females With Adolescent Idiopathic Scoliosis.

STUDY DESIGN: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) included skeletally immature high-risk patients with adolescent idiopathic scoliosis (AIS) with moderate curve sizes (20°- 40°). BrAIST was a multicenter, controlled trial using both randomized and preference treatment arms into either an observation group or a brace treatment group. OBJECTIVE: The aim of this study was to analyze and compare body image and quality-of-life (QOL) in female AIS patients who were observed or treated with a brace. SUMMARY OF BACKGROUND DATA: Brace treatment is an effective means for controlling progressive scoliosis and preventing the need for surgery, but there is no consensus regarding the effect of brace treatment on body image or on QOL in adolescents with AIS. METHODS: Data from female BrAIST patients in the randomized (n = 132) or preference (n = 187) arms and were observed (n = 120) or brace treated (n = 199) were analyzed. Patients completed the Spinal Appearance Questionnaire (SAQ) and the Pediatric Quality of Life Inventory (PedsQOL) 4.0 Generic Scales at baseline and 6 month follow-up visits up to 2 years. Items on the SAQ measured three body image constructs (self, ideal, and overall). The PedsQOL measured health, activities, feelings, social factors, and school. RESULTS: . In general, there were no significant differences within or between study arms or treatments regarding body image or QOL through 2 years of follow-up. Poorer body image was significantly correlated with poorer QOL during the first 2 years of follow-up regardless of study arm or treatment. Patients who crossed-over to a different treatment and patients with largest Cobb angles ≥ 40 degrees had significantly poorer body image, in particular self-body image, compared with those that did not. CONCLUSION: This study does not support findings from previous research indicating that wearing a brace has a negative impact on or is negatively impacted by body image or QOL. LEVEL OF EVIDENCE: 2.

Consistency of quantitative scores of hypoglycemia severity and glycemic lability and comparison with continuous glucose monitoring system measures in long-standing type 1 diabetes.

BACKGROUND: In long-standing type 1 diabetes (T1D), loss of endogenous insulin secretion and glucose dysregulation can lead to severe hypoglycemia and associated complications. Here, we report the serial consistency and the correlation between different scores that characterize glucose dysregulation using self-monitoring of blood glucose (SMBG), in a cohort of T1D individuals being evaluated for transplant eligibility in Clinical Islet Transplantation Consortium trials. SUBJECTS AND METHODS: In total, 152 C-peptide-negative T1D subjects with at least one severe hypoglycemia episode in the prior year documented SMBG at enrollment and every 6 months until deemed ineligible or transplanted. SMBG was used to calculate the HYPO score, Lability Index (LI), and mean amplitude of glycemic excursion (MAGE). Additionally, a blinded continuous glucose monitoring system (CGMS) was worn for 72 h at enrollment and every 12 months. RESULTS: In this cohort, LI was the most consistent (intraclass correlation coefficient=0.70) over time, followed by the HYPO score (0.51), with MAGE being the least consistent (0.36). Although MAGE and LI were highly correlated with each other, neither correlated with CGMS SD or glucose coefficient of variation (CV). Subjects spent a median of 97 min/day at <54 mg/dL using CGMS. The HYPO score correlated with CGMS time below 54 mg/dL and glucose CV. CONCLUSIONS: The HYPO score and LI are more consistent than MAGE in patients with established T1D experiencing severe hypoglycemic events and may be especially useful both for identifying subjects experiencing the greatest difficulty in maintaining glycemic control and for longitudinal assessment of novel interventions.