Elevated serum insulin-like growth factor 1 in recurrent aphthous stomatitis.

Over 100 million Americans experience recurrent aphthous stomatitis (RAS) at some point in life. To develop targeted drugs for RAS treatment, it is critical to identify its etiology. We determined if serum insulin-like growth factor 1 (IGF-1) and related factors are associated with RAS, because both RAS prevalence and IGF-1 are highest during puberty. We analyzed data from 1,480 Third National Health and Nutrition Examination Survey participants aged 20-40 years. Participants with a history of diabetes or lupus, cotinine levels 6 ng/ml or higher or glycemia 110 mg/dl or higher were excluded. We compared levels of IGF-1, IGFBP-3, leptin, and insulin in participants with a positive vs. negative RAS history in the prior 12 months. We used logistic regression in SAS/SUDAAN to account for the complex sampling design. The odds of a positive RAS history were 1.31 times higher for every 100 ng/ml increase in serum IGF-1. This association persisted after adjustment for age, race/ethnicity, medication intake, body mass index, insulin, leptin, glycemia, and income (adjusted OR = 1.30, 95% CI [1.06, 1.60]; p = 0.013). The odds of a positive RAS history were also higher among non-Hispanic white compared with non-Hispanic black participants (adjusted OR = 4.37, 95% CI [3.00, 6.38]). Leptin, IGFBP-3, and insulin levels did not differ by RAS status. The significantly higher IGF-1 levels in participants with a positive RAS history compared with controls suggest a possible role of the IGF-1 pathway in RAS etiology.

Verification of association of elevated serum IDO enzyme activity with acute rejection and low CD4-ATP levels with infection.

BACKGROUND: Both acute rejection (AR) and major infection events (MIE) can reduce long-term allograft survival. We assessed the simultaneous efficacy of serum and urine biomarker indoleamine 2,3-dioxygenase (IDO) enzyme activity and peripheral blood CD4-ATP levels for AR and MIE association, respectively. METHODS: We prospectively tested 217 blood and 167 urine serial samples, collected monthly for 12 months after transplantation from 29 consecutive children receiving a kidney transplant. The indoleamine 2,3-dioxygenase activity was assessed by mass spectrometry assays using the ratio of product L-kynurenine (kyn) to substrate tryptophan (trp). Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with AR, MIE, or stable group (no events) in the next 30 days. RESULTS: Using absolute cutoffs and allocating to samples to AR, MIE, or stable group, mean serum kyn/trp ratios were significantly elevated in the group that experienced AR (P=0.0007). Similarly, peripheral blood CD4-ATP levels were significantly lower in the group experiencing MIE (P=0.0351). Urine kyn/trp ratios and blood tacrolimus levels were not different between AR and stable groups. Within-subject analyses, accounting for repeated measures in subjects, also showed that, over time, serum kyn/trp ratios were higher before AR (P=0.031) and blood CD4-ATP levels were lower before MIE (P=0.008). CONCLUSIONS: These results from our pilot discovery group suggest that a panel of biomarkers together can predict overimmunosuppression or underimmunosuppression. Further independent validation in a multicenter cohort is suggested.

Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes.

We sought to determine if autologous umbilical cord blood (UCB) infusion followed by 1 year of supplementation with vitamin D and docosahexaenoic acid (DHA) can preserve C-peptide in children with type 1 diabetes. We conducted an open-label, 2:1 randomized study in which 15 type 1 diabetes subjects with stimulated C-peptide > .2 pmol/mL received either (1) autologous UCB infusion, 1 year of daily oral vitamin D (2000 IU), and DHA (38 mg/kg) and intensive diabetes management or (2) intensive diabetes management alone. Primary analyses were performed 1 year after UCB infusion. Treated (N = 10) and control (N = 5) subjects had median ages of 7.2 and 6.6 years, respectively. No severe adverse events were observed. Although the absolute rate of C-peptide decline was slower in treated versus control subjects, intergroup comparisons failed to reach significance (P = .29). Area under the curve C-peptide declined and insulin use increased in both groups (P < .01). Vitamin D levels remained stable in treated subjects but declined in control subjects (P = .01). DHA levels rose in treated subjects versus control subjects (P = .003). CD4/CD8 ratio remained stable in treated subjects but declined in control subjects (P = .03). No changes were seen in regulatory T cell frequency, total CD4 counts, or autoantibody titers. Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide. Lack of significance may reflect small sample size. Future efforts will require expansion of specific immunoregulatory cell subsets, optimization of combined immunoregulatory and anti-inflammatory agents, and larger study cohorts.

Validation of anamnestic diagnostic criteria for recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is characterized by painful recurrent oral ulcers and is typically diagnosed via history and clinical examination. Our aim was to validate a set of anamnestic diagnostic criteria (RASDX) to increase the accuracy of RAS diagnosis, particularly when a clinical examination is not feasible. METHODS: Participants were enrolled during an unmatched case-control study. RASDX consisted of an initial phone screening using standardized questionnaires and recognition of RAS photographs in the clinic. The proportion of agreement with an examination by an oral medicine expert was calculated. RESULTS: A total of 115 participants were scheduled for a clinical diagnostic visit and 11 were withdrawn. The remaining 104 participants were aged 18-50 years, 54% women, 64% White and 20% Hispanic. Of these, all 49 controls with negative RASDX had no clinical ulcers. Of the 54 cases diagnosed with RAS by RASDX, 53 were clinically confirmed to have RAS lesions (99% agreement; exact one-sided 95% CI = 95-100%). CONCLUSIONS: RASDX, based on a combination of history and photograph recognition, was highly accurate compared with a diagnosis that employed an oral examination.

Plasma concentration of N-terminal pro-atrial and N-terminal pro-brain natriuretic peptides and fluid balance in children with bronchiolitis.

The aim of this study was to evaluate the plasma levels of N-Terminal pro-brain natriuretic peptide (N-BNP), N-Terminal pro-atrial natriuretic peptide (N-ANP) and antidiuretic hormone (ADH) over time and their relationship to clinical indicators in hospitalized children with bronchiolitis. Prospective crossover clinical investigation. Hospitalized children in a university-affiliated hospital. Twenty-seven children (birth to 24 mo) with first episode of bronchiolitis and 34 age-matched healthy controls. Daily blood samples up to five consecutive days were obtained for N-BNP, N-ANP and ADH in the bronchiolitis group and on the initial blood draw in the control group. Daily total fluid intake, net fluid balance and clinical bronchiolitis severity levels were recorded. N-BNP and N-ANP levels were measured by enzyme-linked immunosorbent assay. ADH levels were measured by a double antibody technique. The mean age (months ± SD) in the bronchiolitis group was 4.2 ± 5.9 mo and 12.0 ± 6.1 mo in the control group; 51.9% of bronchiolitis patients were positive for respiratory syncytial virus (RSV). In patients with bronchiolitis on admission, plasma N-BNP measurements (mean ± SD) were elevated (996.0 ± 570.2 fmol/mL) compared to controls (552.7 ± 264.7 fmol/mL P < 0.005). Serum N-ANP levels were also initially elevated (3,889 ± 1,769.7 fmol/mL) compared to controls (2,173 ± 912 fmol/mL P < 0.005). The serum levels of N-BNP and N-ANP remained significantly elevated from day 2 through day 5. Similarly, ADH levels were significantly higher on admission in the bronchiolitis group (10 ± 7.49 pg/mL) vs. the control group (5.8 ± 5.5 pg/mL P < 0.05), but quickly decreased from day 2 through day 5. N-BNP, N-ANP and ADH concentrations were elevated in hospitalized children with bronchiolitis at admission. Based on our observation, judicious fluid management is indicated in children hospitalized with bronchiolitis.

Autologous umbilical cord blood transfusion in young children with type 1 diabetes fails to preserve C-peptide.

OBJECTIVE: We conducted an open-label, phase I study using autologous umbilical cord blood (UCB) infusion to ameliorate type 1 diabetes (T1D). Having previously reported on the first 15 patients reaching 1 year of follow-up, herein we report on the complete cohort after 2 years of follow-up. RESEARCH DESIGN AND METHODS: A total of 24 T1D patients (median age 5.1 years) received a single intravenous infusion of autologous UCB cells and underwent metabolic and immunologic assessments. RESULTS: No infusion-related adverse events were observed. ß-Cell function declined after UCB infusion. Area under the curve C-peptide was 24.3% of baseline 1 year postinfusion (P < 0.001) and 2% of baseline 2 years after infusion (P < 0.001). Flow cytometry revealed increased regulatory T cells (Tregs) (P = 0.04) and naive Tregs (P = 0.001) 6 and 9 months after infusion, respectively. CONCLUSIONS: Autologous UCB infusion in children with T1D is safe and induces changes in Treg frequency but fails to preserve C-peptide.

Fecal microbiota in premature infants prior to necrotizing enterocolitis.

Intestinal luminal microbiota likely contribute to the etiology of necrotizing enterocolitis (NEC), a common disease in preterm infants. Microbiota development, a cascade of initial colonization events leading to the establishment of a diverse commensal microbiota, can now be studied in preterm infants using powerful molecular tools. Starting with the first stool and continuing until discharge, weekly stool specimens were collected prospectively from infants with gestational ages ≤32 completed weeks or birth weights≤1250 g. High throughput 16S rRNA sequencing was used to compare the diversity of microbiota and the prevalence of specific bacterial signatures in nine NEC infants and in nine matched controls. After removal of short and low quality reads we retained a total of 110,021 sequences. Microbiota composition differed in the matched samples collected 1 week but not <72 hours prior to NEC diagnosis. We detected a bloom (34% increase) of Proteobacteria and a decrease (32%) in Firmicutes in NEC cases between the 1 week and <72 hour samples. No significant change was identified in the controls. At both time points, molecular signatures were identified that were increased in NEC cases. One of the bacterial signatures detected more frequently in NEC cases (p<0.01) matched closest to γ-Proteobacteria. Although this sequence grouped to the well-studied Enterobacteriaceae family, it did not match any sequence in Genbank by more than 97%. Our observations suggest that abnormal patterns of microbiota and potentially a novel pathogen contribute to the etiology of NEC.

Control in the middle (CIM) for three-period crossover studies.

Three-period crossover studies can be efficient and convenient methods of conducting Phase II clinical trials. Non-randomly placing control in the middle (CIM) has not been practiced but may be extremely useful in studies testing herbal products for which placebos are not available, or for distinguishing between behavioral and biological effects. Furthermore, this design can serve as a valuable addition to classical studies of either (a) two competing treatments or (b) treatment versus placebo versus an open label "nothing" as the control. Therefore, we propose rigorous designs that will help practitioners efficiently answer research questions where (1) two active treatments need to be compared against each other with treatment vs. placebo comparisons being of secondary importance; (2) a single active treatment needs to be tested where no placebo is available; or (3) the placebo effect is of interest in a treatment vs. placebo trial. For studies where no placebo is available, deception will be required, with participants told that in one randomly selected period (#1 or #3) they will receive the active treatment, and that they will receive a new experimental inert placebo in the other period. Assuming this design is approved by an ethics committee, it can be very useful in biomedical research.

Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels: prediction of acute rejection vs. viral replication events.

Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.

Long-term pain, stiffness, and functional disability after total knee arthroplasty with and without an extended ambulatory continuous femoral nerve block: a prospective, 1-year follow-up of a multicenter, randomized, triple-masked, placebo-controlled trial.

BACKGROUND: Previously, we have demonstrated that extending a continuous femoral nerve block (cFNB) from overnight to 4 days after total knee arthroplasty (TKA) provides clear benefits during the infusion, but not subsequent to catheter removal. However, there were major limitations in generalizing the results of that investigation, and we subsequently performed a very similar study using a multicenter format, with many health care providers, in patients on general orthopedic wards, thus greatly improving inference of the results to the general population. Not surprisingly, the perioperative/short-term outcomes differed greatly from the first, more limited study. We now present a prospective follow-up study of the previously published, multicenter, randomized controlled clinical trial to investigate the possibility that an extended ambulatory cFNB decreases long-term pain, stiffness, and functional disability after TKA, which greatly improves inference of the results to the general population. METHODS: Subjects undergoing TKA received a cFNB with ropivacaine 0.2% from surgery until the following morning, at which time patients were randomized to continue either perineural ropivacaine (n=28) or normal saline (n=26). Patients were discharged with their catheter and a portable infusion pump, and catheters were removed on postoperative day 4. Health-related quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis Index preoperatively and then at 7 days, as well as 1, 2, 3, 6, and 12 months after surgery. This index evaluates pain, stiffness, and physical functional disability. For inclusion in the analysis, we required a minimum of 4 of the 6 time points, including day 7 and at least 2 of months 3, 6, and 12. RESULTS: The 2 treatment groups had similar Western Ontario and McMaster Universities Osteoarthritis scores for the mean area-under-the-curve calculations (point estimate for the difference in mean area under the curve for the 2 groups [overnight infusion group - extended infusion group]=3.8; 95% confidence interval, -3.8 to +11.3; P=0.32) and at all individual time points (P>0.05). CONCLUSIONS: This investigation found no evidence that extending an overnight cFNB to 4 days improves (or worsens) subsequent pain, stiffness, or physical function after TKA in patients of multiple centers convalescing on general orthopedic wards.

A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy.

Severe hypoxic-ischemic encephalopathy (HIE) is a devastating condition that can lead to mortality and long-term disabilities in term newborns. No rapid and reliable laboratory test exists to assess the degree of neuronal injury in these patients. We propose two possible biomarkers: 1) phosphorylated axonal neurofilament heavy chain (pNF-H) protein, one of the major subunits of neurofilaments, found only in axonal cytoskeleton of neurons and 2) Ubiquitin C-terminal hydrolase 1 (UCHL1 protein) that is heavily and specifically concentrated in neuronal perikarya and dendrites. High-serum pNF-H and UCHL1 levels are reported in subarachnoid hemorrhage and traumatic brain injury, suggesting that they are released into blood following neuronal injury. We hypothesized that serum pNF-H and UCHL1 were higher in neonates with moderate-to-severe HIE than in healthy neonates. A time-limited enrollment of 14 consecutive patients with HIE and 14 healthy controls was performed. UCHL1 and pNF-H were correlated with clinical data and brain MRI. UCHL1 and pNF-H serum levels were higher in HIE versus controls. UCHL1 showed correlation with the 10-min Apgar score, and pNF-H showed correlation with abnormal brain MRI. Our findings suggest that serum UCHL1 and pNF-H could be explored as diagnostic and prognostic tools in neonatal HIE.

A multicenter, randomized, triple-masked, placebo-controlled trial of the effect of ambulatory continuous femoral nerve blocks on discharge-readiness following total knee arthroplasty in patients on general orthopaedic wards.

A continuous femoral nerve block (cFNB) involves the percutaneous insertion of a catheter adjacent to the femoral nerve, followed by a local anesthetic infusion, improving analgesia following total knee arthroplasty (TKA). Portable infusion pumps allow infusion continuation following hospital discharge, raising the possibility of decreasing hospitalization duration. We therefore used a multicenter, randomized, triple-masked, placebo-controlled study design to test the primary hypothesis that a 4-day ambulatory cFNB decreases the time until each of three predefined readiness-for-discharge criteria (adequate analgesia, independence from intravenous opioids, and ambulation 30m) are met following TKA compared with an overnight inpatient-only cFNB. Preoperatively, all patients received a cFNB with perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomized to either continue perineural ropivacaine (n=39) or switch to normal saline (n=38). Patients were discharged with their cFNB and portable infusion pump as early as postoperative day 3. Patients who were given 4 days of perineural ropivacaine attained all three criteria in a median (25th-75th percentiles) of 47 (29-69)h, compared with 62 (45-79)h for those of the control group (Estimated ratio=0.80, 95% confidence interval: 0.66-1.00; p=0.028). Compared with controls, patients randomized to ropivacaine met the discharge criterion for analgesia in 20 (0-38) versus 38 (15-64)h (p=0.009), and intravenous opioid independence in 21 (0-37) versus 33 (11-50)h (p=0.061). We conclude that a 4-day ambulatory cFNB decreases the time to reach three important discharge criteria by an estimated 20% following TKA compared with an overnight cFNB, primarily by improving analgesia.

Two-thumb technique is superior to two-finger technique during lone rescuer infant manikin CPR.

OBJECTIVE: Infant CPR guidelines recommend two-finger chest compression with a lone rescuer and two-thumb with two rescuers. Two-thumb provides better chest compression but is perceived to be associated with increased ventilation hands-off time. We hypothesized that lone rescuer two-thumb CPR is associated with increased ventilation cycle time, decreased ventilation quality and fewer chest compressions compared to two-finger CPR in an infant manikin model. DESIGN: Crossover observational study randomizing 34 healthcare providers to perform 2 min CPR at a compression rate of 100 min(-1) using a 30:2 compression:ventilation ratio comparing two-thumb vs. two-finger techniques. METHODS: A Laerdal Baby ALS Trainer manikin was modified to digitally record compression rate, compression depth and compression pressure and ventilation cycle time (two mouth-to-mouth breaths). Manikin chest rise with breaths was video recorded and later reviewed by two blinded CPR instructors for percent effective breaths. Data (mean+/-SD) were analyzed using a two-tailed paired t-test. Significance was defined qualitatively as p< or =0.05. RESULT: Mean % effective breaths were 90+/-18.6% in two-thumb and 88.9+/-21.1% in two-finger, p=0.65. Mean time (s) to deliver two mouth-to-mouth breaths was 7.6+/-1.6 in two-thumb and 7.0+/-1.5 in two-finger, p<0.0001. Mean delivered compressions per minute were 87+/-11 in two-thumb and 92+/-12 in two-finger, p=0.0005. Two-thumb resulted in significantly higher compression depth and compression pressure compared to the two-finger technique. CONCLUSION: Healthcare providers required 0.6s longer time to deliver two breaths during two-thumb lone rescuer infant CPR, but there was no significant difference in percent effective breaths delivered between the two techniques. Two-thumb CPR had 4 fewer delivered compressions per minute, which may be offset by far more effective compression depth and compression pressure compared to two-finger technique.

Maternal voice and short-term outcomes in preterm infants.

This study explored effects of exposure to maternal voice on short-term outcomes in very low birth weight preterm infants cared for within an neonatal intensive care unit (NICU) without an ongoing program of developmental care. Using a comparative design, 53 infants born during their 27th to 28th postmenstrual week were sampled by convenience. Experimental groups were exposed to maternal voice during two developmental time periods. Group 1 listened to a recording of their mothers reciting a rhyme from 28 to 34 postmenstrual weeks. Group 2 waited 4 weeks and heard the recording from 32 to 34 weeks. The control group received routine care. The primary analysis of combined experimental groups compared to the control group revealed that the experimental infants experienced significantly fewer episodes of feeding intolerance and achieved full enteral feeds quicker compared to the control group. Further, in an analysis evaluating all three groups separately, it was noted that Group 1 experienced significantly fewer episodes of feeding intolerance compared to the control group. Study findings warrant further investigation of exposure to maternal voice and the developmental timing at which exposure is begun.

Intestinal microbial ecology in premature infants assessed with non-culture-based techniques.

OBJECTIVES: To use high throughput techniques to analyze intestinal microbial ecology in premature neonates, who are highly susceptible to perturbations of the luminal environment associated with necrotizing enterocolitis (NEC) and late-onset sepsis. STUDY DESIGN: With non-culture-based techniques, we evaluated intestinal microbiota shortly after birth and during hospitalization in 23 neonates born at 23 to 32 weeks gestational age. Microbiota compositions were compared in 6 preterm infants in whom NEC, signs of systemic inflammation, or both developed with matched control subjects by using 16S ribosomal RNA pyrosequencing. RESULTS: Microbial DNA was detected in meconium, suggesting an intrauterine origin. Differences in diversity were detected in infants whose mothers intended to breast feed (P = .03), babies born to mothers with chorioamnionitis (P = .06), and in babies born at <30 weeks gestation (P = .03). A 16S ribosomal RNA sequence analysis detected Citrobacter-like sequences only in cases with NEC (3 of 4) and an increased frequency of Enterococcus-like sequences in cases and Klebsiella in control subjects (P = .06). The overall microbiota profiles in cases with NEC were not distinguishable from that in control subjects. CONCLUSIONS: Microbial DNA in meconium of premature infants suggests prenatal influences.

Sleep disordered breathing in infants with Prader-Willi syndrome during the first 6 weeks of growth hormone therapy: a pilot study.

BACKGROUND: Sleep-related breathing disorders are common in individuals with Prader-Willi syndrome (PWS). The US Food and Drug Administration approved the use of growth hormone in PWS in 2000. Many infants with PWS are being started on growth hormone therapy, but no data exist on the respiratory effects of growth hormone treatment in this age group. STUDY OBJECTIVES: To perform overnight polysomnographic studies to evaluate the effects of growth hormone on sleep-related breathing in infants with PWS. METHODS: Pilot study evaluating overnight polysomnography before and 6 weeks after initiation of growth hormone therapy at a dose of 1 mg/m2 per day in 20 infants from 2 to 21 months of age with genetically confirmed PWS. Polysomnography results were analyzed for frequency and severity of obstructive and central apnea and hypopnea events and the overall apnea-hypopnea index. RESULTS: When data were analyzed for the total group, there were no significant changes in sleep-related disorders before and after institution of growth hormone therapy. However, 12 infants had an increase in the frequency of obstructive events associated with either upper respiratory infections or a diagnosis of gastroesophageal reflux at the second sleep study (after institution of growth hormone therapy). Resolution of these conditions was associated with normalization of polysomnography results on follow-up studies. CONCLUSIONS: Overall, growth hormone therapy, per se, had no significant effect on sleep related-breathing disorders in infants with PWS. Infants with upper respiratory infections of gastroesophageal reflux may be at risk for developing more obstructive events after beginning growth hormone treatment. We recommend close monitoring of infants with PWS after they begin growth hormone therapy, especially when they have upper respiratory infections.

A pilot study of Octreotide LAR vs. octreotide tid for pain and quality of life in chronic pancreatitis.

CONTEXT: Chronic abdominal pain is the most difficult management issue in patients with chronic pancreatitis. Recently, a long-acting depo-formulated version of octreotide has been developed that can be given as a once monthly intramuscular injection, Octreotide LAR(R) (O-LAR) rather than as a thrice daily subcutaneous injection (octreotide short-acting, O-SA). OBJECTIVE: To see if O-LAR is similar in efficacy to O-SA in the treatment of painful chronic pancreatitis in a small open-label, unblinded pilot study. PATIENTS: Seven advanced chronic pancreatitis patients with daily, severe abdominal pain who had previously responded to O-SA were recruited from the pancreas clinics of the University of Florida and monitored for one month on O-SA and for four months while on O-LAR. Each patient served as his/her own control as this was a paired data set. MAIN OUTCOME MEASURES: 1) Daily VAS scores; 2) daily morphine equivalents; 3) monthly health related quality of life chronic pancreatitis surveys; 4) daily diaries of work/pleasurable activities missed or hospitalization/Emergency Department visits. RESULTS: Average daily VAS scores for patients during O-SA therapy were 4.50+/-2.28 and during the fourth month of O-LAR therapy, 3.86+/-2.11, difference -0.64+/-0.80 (P=0.078). Average daily morphine equivalents were not dissimilar at 124.3+/-177.3 mg during O-SA therapy and 131.6+/-194.3 mg during O-LAR therapy; difference 7.3+/-17.5 mg P=0.310. Health related quality of life chronic pancreatitis scores were not significantly changed when moving from O-SA to O-LAR. Adverse events were rare. CONCLUSIONS: Octreotide LAR(R) may be a reasonable substitute for tid octreotide in treating chronic pancreatitis pain. Further, larger studies would be useful to better characterize the role of Octreotide LAR(R) in the management of chronic pancreatitis pain.

Improved chest recoil using an adhesive glove device for active compression-decompression CPR in a pediatric manikin model.

OBJECTIVE: We developed an adhesive glove device (AGD) to perform ACD-CPR in pediatric manikins, hypothesizing that AGD-ACD-CPR provides better chest decompression compared to standard (S)-CPR. DESIGN: Split-plot design randomizing 16 subjects to test four manikin-technique models in a crossover fashion to AGD-ACD-CPR vs. S-CPR. Healthcare providers performed 5min of CPR with 30:2 compression:ventilation ratio in the four manikin models: (1) adolescent; (2) child two-hand; (3) child one-hand; and (4) infant two-thumb. METHODS: Modified manikins recorded compression pressure (CP), compression depth (CD) and decompression depth (DD). The AGD consisted of a modified oven mitt with an adjustable strap; a Velcro patch was sewn to the palmer aspect. The counter Velcro patch was bonded to the anterior chest wall. For infant CPR, the thumbs of two oven mitts were stitched together with Velcro. Subjects were asked to actively pull up during decompression. Subjects' heart rate (HR), respiratory rate (RR) and recovery time (RT) for HR/RR to return to baseline were recorded. Subjects were blinded to data recordings. Data (mean+/-SEM) were analyzed using a two-tailed paired t-test. Significance was defined qualitatively as P< or =0.05. RESULTS: Mean decompression depth difference was significantly greater with AGD-ACD-CPR compared to S-CPR; 38-75% of subjects achieved chest decompression to or beyond baseline. AGD-ACD-CPR provided 6-12% fewer chest compressions/minute than S-CPR group. There was no significant difference in CD, CP, HR, RR and RT within each group comparing both techniques. CONCLUSION: A simple, inexpensive glove device for ACD-CPR improved chest decompression with emphasis on active pull in manikins without excessive rescuer fatigue. The clinical implication of fewer compressions/minute in the AGD group needs to be evaluated.

Early childhood obesity is associated with compromised cerebellar development.

As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

Pediatric Atorvastatin in Diabetes Trial (PADIT): a pilot study to determine the effect of atorvastatin on arterial stiffness and endothelial function in children with type 1 diabetes mellitus.

Fifty-one children with type 1 diabetes mellitus (DM1) participated in a double blinded, randomized, cross-over pilot study to determine whether 12 weeks of daily atorvastatin (20 mg daily) would reduce arterial stiffness and improve endothelial function. Secondary analysis demonstrated potential reduction of arterial stiffness following atorvastatin therapy (p = 0.06). Additional long-term prospective studies with larger numbers of patients are needed.