Browsing by Subject "Pediatric"
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Item Central Blood Pressure Regulation in Relation to Obesity in Youth(2017-08) Hultgren, NeilAbstract Introduction Measures of central blood pressure (BP) are hypothesized to be positively associated with obesity status in youth. However, few studies have addressed this topic with a large sample size and wide range of BMI values. Methods A total of 310 participants (males/females =151/159) aged of 8 to 18 years old (mean±SD: 12.8±2.7 years) were recruited. Height (cm) and weight (kg) were measured using a wall-mounted stadiometer and an electric scale. Body mass index (BMI) was calculated (kg/m2) and obesity status was determined using age – and sex- derived BMI percentile (BMI%) with the following categories: normal weight (NW) represented as <85th BMI percentile; overweight/obesity (OW/OB) represented as between 85th to < 1.2 times the 95th BMI percentile); severe obesity (SO) represented as ≥ 1.2 times the 95th BMI percentile. Dual energy X-ray absorptiometry (DXA) was used to measure body composition. Brachial systolic (SBP) and diastolic (DBP) blood pressure was measured with an automated cuff. Central BP was obtained from SphygmoCor MM3 systems, which utilizes applanation tonometry to derive radial-aorta SBP (r-a SBP), radial-aorta DBP (r-a DBP), carotid-aorta SBP (c-a SBP), and carotid-aorta DBP (c-a DBP). Central BP measures were compared across obesity groups using ANCOVA with post-hoc Tukey HSD, adjusted for age, Tanner stage, sex, and race, with further adjustment of height for brachial BP. Unadjusted Pearson correlations examined the relationship between central BP measures with obesity (BMI, BMI%, body fat (%), visceral fat mass (kg)). Linear regression analyses examined the association between body fat (%) and visceral fat mass (kg) with brachial and central SBP and DBP after adjusting for age, Tanner stage, sex, and race, with height included for brachial BP. Results There were 120 NW, 89 OW/OB, and 99 SO participants. Body fat (%) was significantly different (p<0.001) among all obesity groups: NW (25.1±6.1 %), OW/OB (39.5±7.2 %), SO (48.0±4.9 %). Brachial SBP (bSBP), r-a SBP, and c-a SBP significantly increased (p<0.001 all) with increasing obesity status. BMI was significantly correlated (p<0.001 all) with bSBP (r=0.64), r-a SBP (r=0.57), and c-a SBP (r=0.52). BMI%, body fat (%), and visceral fat mass (kg) were also all significantly correlated to all brachial and Central BP measures. In multiple regression models, higher values of body fat (%) were significantly associated (all p<0.001) with higher brachial (r=0.66) and central SBP (r-a r=0.59) (c-a r=0.55) as well as brachial (r=0.44) and central DBP (r-a r=0.42) (c-a r=0.46). Higher values of visceral fat mass (kg) were significantly associated (all p<0.001) with higher brachial (r=0.61) and central SBP (r-a r=0.60) (c-a r=0.55) as well as brachial (r=0.39) and central DBP (r-a r=0.42) (c-a r=0.44). Older age was significantly associated with higher r-a SBP (r=0.59. p<0.001) and c-a SBP (r=0.55, p<0.01). Conclusion Central BP, regardless of measurement site, is highly associated with Obesity status (BMI, BMI%, body fat (%), and visceral fat mass (kg)) and hypertension status among youth.Item Comparing cutaneous sensory reactivity between children with and without global developmental delay(2014-05) Barney, Chantel C.Our scientific understanding of pain among individuals with developmental delays and disabilities with associated intellectual, motor, and/or communicative impairments is limited because of the difficulty in reliably and validly assessing a complex experience when verbal self-report is compromised. One approach is to rely on non-verbal pain behaviors. There has been no work comparing non-verbal pain behavior of very young children with global developmental delays with age and gender matched typically developing children. This study used a calibrated tactile sensory test to provide a mechanisms-based approach to indirectly compare the functionality of the somatosensory pathways in children with and without global developmental delay (GDD). A case control design was used to test the reactivity of 20 children with GDD (60% male; M age = 4.91 years, SD=1.13) and 20 typically developing children (60% male; M age = 3.49 years, SD=1.08). Sensory reactivity was indexed by vocal, facial, and body activity during the sensory test. This sample of children with GDD exhibited significantly greater duration of overall reactivity during the sensory test (p<.01) and specifically exhibited greater vocal (p<.01) and body (p<.05) reactivity compared to controls. For children with GDD, severity of self-injurious behavior significantly correlated with vocal (r=.58, p=.01) and body (r=.56, p<.05) reactivity during the pin prick trial. Children with GDD who were more reactive to the sensory test had significantly reduced epidermal nerve fiber densities (p<.05). This study was the first to measure the behavioral response of children with GDD to a calibrated sensory test and in comparison to a typically developing control group. The results of the study provide information about the physiology and nociceptive pathways of children with GDD. Despite limitations in verbal self-report, children with GDD exhibited non-verbal pain behaviors to signal their reactivity to a calibrated sensory test.Item Effect of obesity on hepatic drug metabolism(2013-09) Chiney, Manoj ShriramObesity has increased markedly over the last few decades and is now a major public health crisis in the U.S. affecting over 1/3 of the US population. Optimization of dosing in obese individuals is a challenge due to the lack of knowledge regarding changes in the pharmacokinetics (PK) of therapeutic agents in obese individuals. Thus the aim of this thesis was to determine the effect of obesity on drug metabolism and evaluate methods that could potentially predict changes in pharmacokinetics in the obese population. The impact of obesity on drug metabolism in children has not been determined and our clinical study (Chapter 2) was the first of its kind to examine the effect of childhood obesity on CYP1A2, CYP2D6, CYP3A4, xanthine oxidase, and NAT2 activity using caffeine and dextromethorphan as probe drugs. Our results conclusively indicate that obesity results in an elevation of xanthine oxidase and NAT2 enzyme activities in obese children as compared to lean children, whereas there was no difference in CYP1A2, CYP2D6 and CYP3A4 activity between obese and lean children. This study provides a potential mechanism of altered 6-mercaptopurine exposure in the obese pediatric cancer population. While clinical studies would provide the most optimum method to predict clearance of therapeutic agents in humans, studies have reported that clearance can also be predicted using animal data. In Chapter 3, we examined mouse, rat and porcine model of obesity in order to determine the utility of these animal models to predict PK in obese humans and to identify a model that would best reflect the human obesity mediated changes in drug metabolism. The study indicated species dependent differences in CLint of various drugs that were due to, either changes in expression of drug metabolizing enzymes or changes in enzyme substrate affinity. The study demonstrated that obesity can alter enzyme activity in a species and model dependent manner. Furthermore this study identified that the rat High Fat Diet animal model of obesity is the best representation of the obesity mediated alterations in humans. In Chapter 4, in collaboration with Drs. Scott Rector and Jim Perfield, University of Missouri, Columbia, we demonstrated obesity mediated alterations of drug metabolism enzyme activity can be prevented by sterculic oil dietary supplementation. These effects are mediated through signal transduction pathways which regulate CAR and PXR transcription factors. These results establish that obesity mediated changes are biochemically dependent and not weight dependent. In Chapter 5, we developed a proof of concept that would help generate biochemically obese hepatocytes. In absence of hepatocytes from obese individuals, these hepatocytes can be used as a tool to predict obesity mediated changes in drug clearance. Our studies indicate that individually, leptin, resistin, IL-6 and TNF-α can modulate expression of various DMEs in a concentration dependent and isoform specific manner. This study demonstrates that the obesity microenvironment is important in obesity mediated changes in drug metabolism. Additional studies would help establish a more robust method to generate and validate these obese hepatocytes. In summary, the work in this thesis has helped identify the drug metabolism enzymes that are altered in the obese children, the utility of using animal models of obesity as tools to study the impact of obesity on pharmacokinetics/pharmacodynamics, proven that it is possible to reverse obesity mediated changes in drug metabolism and developed an in vitro model that may be used to predict changes in drug disposition in the obese population. These findings are important for to better develop dosing strategies in obese humans with concomitant disease.Item Method to Determine Compressive Bending Performance in Static and Fatigue Loading for Pediatric Non-Fusion Devices(2016-01) Foltz, MaryBackground: Early onset scoliosis is a three-dimensional deformity of the spine and trunk – diagnosed before the age of 10 – and occurs in 3 to 5 out of 100,000 infant and juvenile populations. Surgical intervention is often necessary for pediatric patients with severe curvatures. During thesis procedures, spinal rods – known as pediatric non-fusion devices (i.e. growing rods) – are placed in the patients to allow for spinal growth. ASTM standards exist for fusion constructs. Growing-rod constructs place greater demands on the rods as no fusion is performed and the rods are continually loaded. Also, the constructs are serially lengthened at 6-month intervals placing additional demands on the construct. Currently, there are no standards on how to develop and utilize a finite element model – to predict durability of commonly used constructs within the patient. Methods: Finite element models representing static compression bending were implemented using Abaqus CAE (Dassault Systemés Simulia Corporation, Providence, Rhode Island). The model geometry and loading was based on ASTM standard 1537 and 136. The models were created with C3D8R type elements. The model applied a controlled displacement until failure or contact occurred between the superior and inferior UHMWPE blocks. Failure was defined as the point at which permanent deformation of the construct occurs, due to fracture, plastic deformation, or slip. Eight constructs were analyzed based on the rod material (titanium and cobalt chrome), active length (76-mm and 376-mm), and construct type (F1717 and growing-rod). Results: The force-displacement curves and maximum principle stress for each whole model were evaluated. The longer active lengths required a smaller force for failure. Failure at the pedicle screw head was found on each model. Conclusions: A new ASTM standard for growing-rod constructs should be created based off of a longer active length, the overlap of the rod connectors, and location of the rod connectors.Item Pediatric nurses‘ grief experience: its relationship with burnout and job satisfaction.(2010-07) Adwan, Jehad ZakiThe goal of this correlational study on 120 pediatric nurses was to examine relationships among grief experience following patients death, burnout, job satisfaction, and other environmental variables. Measurement used the Revised Grief Experience Inventory (RGEI), Maslach Burnout Inventory (MBI), Index of Work Satisfaction (IWS) and Demographic Information Form (DIF). Results showed grief to have significant correlations; positive with burnout, negative with job satisfaction. Some nurses tended to have significantly higher emotional exhaustion if more of their primary patients died and higher guilt if dying patients were younger. Conclusions suggest a dynamic interaction among grief, burnout, job satisfaction, and environmental variables where they interact and relate to nurses' intention to leave unit, organization, or nursing. Recommendations for practice call for grief intervention and education programs. Recommended future research includes RGEI instrument refinement, evaluation of grief intervention and education programs and their impact on burnout and job satisfaction as outcome variables.Item Preventing Childhood Migraines(2010-07-22) Herseth, JonathanMigraines in children can be a serious problem affecting both life and school. Recurrent headaches on one side of the head or both with throbbing sensation associated with an upset stomach and vomiting, changes in vision, dizziness may indicate migraines. Lifestyle changes can help to decrease these headaches. In some cases, medications may be used to prevent headache or decrease the frequency of headaches for those who do not respond to more conservative efforts to decrease. Topiramate (Topamax) is a medication that has been shown in kids to reduce the frequency and the severity of headaches. Some side effects may be nervousness, electrolyte imbalance, emotional changes and kidney stones. Other medications have also been used with good results.Item Role of Gender, Age, Pubertal Status and Adiposity on Endothelium-Independent Dilation in Children and Adolescents(2015-05) Zavala, HananThis study examined how gender, age, pubertal status, and obesity influence endothelium-independent dilation (EID) in youth. Three hundred twenty-two healthy youth (142 females), aged 9 to 18 years (mean±SEM, age=14.1±0.14years) were included. The change in brachial artery diameter following administration of 0.3mg of sublingual nitroglycerin was measured using conventional ultrasound scanner. Multiple linear regression models were created using the predictors gender, age, BMI-percentile, percent body fat and baseline diameter. Differences between gender, pubertal status and BMI category was conducted using one-way ANOVA. Females had higher EID-area under the curve (EID-AUC) compared to males (p=0.012) but not EID% (p=0.112). Age was a significant predictor of EID% (p=0.04) and EID-AUC (p=0.02) in females but not males. No differences in EID% or EID-AUC were observed across Tanner stage or BMI category. These data suggest that gender differences in EID are apparent early in life, with aging-related changes observable in females, but not males.Item Severe childhood autism: The family lived experience(2016-04) Gorlin, JocelynBackground: There is limited literature that focuses solely on the experiences of families when a child has severe autism and includes data collected from multiple family members. Related review of the literature includes studies addressing family quality of life and qualitative studies on the experience of families with a child who has autism. Objective: The goal of this study was to understand the lived experience of families with children who have severe autism by narrowing the focus to only families of children with severe autism and broadening the interviews to include multiple family members. Method: The study used van Manen’s (2014) phenomenological approach for data collection and analysis based on in-depth unstructured interviews of 11 families with 22 family members including mothers, father, grandmothers, an aunt, a sibling, and a friend. Findings: Six essential themes were identified. First, families found autism a mysterious and complex condition. This included the misconception that autism is a mild disability, that autism is an invisible condition, the unpredictable nature of autism, and the challenges of assessing severity. Second, families dealt with startling and severe autism-related behaviors that were often self-injurious, harmed others, and damaged homes. Third, families dealt with profound communication deficits that resulted in isolation between the family and child. Fourth, families experienced unrelenting stress related to their lack of sleep, caring for a child with developmental delays, coordinating myriad health care services, cost and concern for the child’s long-term future. Fifth, extreme isolation from their child, friends, school, the public, and health care providers ensued. Sixth was a strong dependence on families for support and formation of hybrid families which included nuclear and extended families and friends coupled with a compassion that seemed to blossom over time. Conclusion: The findings inform health care providers about the need to recognize and provide better quality of care for children with severe autism and their families. Implications include the importance of education for health care providers on caring for these families. The findings emphasize the importance of developing appropriate health care policy to provide much needed resources for children with severe autism and their families.