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BACKGROUND/OBJECTIVES: Bariatric surgery produces robust weight loss, however, factors associated with long-term weight-loss maintenance among adolescents undergoing Roux-en-Y gastric bypass surgery are unknown. SUBJECTS/METHODS: Fifty adolescents (mean±s.d. age and body mass index (BMI)=17.1±1.7 years and 59±11 kg m-2) underwent Roux-en-Y gastric bypass surgery, had follow-up visits at 1 year and at a visit between 5 and 12 years following surgery (Follow-up of Adolescent Bariatric Surgery at 5 Plus years (FABS-5+) visit; mean±s.d. 8.1±1.6 years). A non-surgical comparison group (n=30; mean±s.d. age and BMI=15.3±1.7 years and BMI=52±8 kg m-2) was recruited to compare weight trajectories over time. Questionnaires (health-related and eating behaviors, health responsibility, impact of weight on quality of life (QOL), international physical activity questionnaire and dietary habits via surgery guidelines) were administered at the FABS-5+ visit. Post hoc, participants were split into two groups: long-term weight-loss maintainers (n=23; baseline BMI=58.2 kg m-2; 1-year BMI=35.8 kg m-2; FABS-5+ BMI=34.9 kg m-2) and re-gainers (n=27; baseline BMI=59.8 kg m-2; 1-year BMI=36.8 kg m-2; FABS-5+ BMI=48.0 kg m-2) to compare factors which might contribute to differences. Data were analyzed using generalized estimating equations adjusted for age, sex, baseline BMI, baseline diabetes status and length of follow-up. RESULTS: The BMI of the surgical group declined from baseline to 1 year (-38.5±6.9%), which, despite some regain, was largely maintained until FABS-5+ (-29.6±13.9% change). The BMI of the comparison group increased from baseline to the FABS-5+ visit (+10.3±20.6%). When the surgical group was split into maintainers and re-gainers, no differences in weight-related and eating behaviors, health responsibility, physical activity/inactivity, or dietary habits were observed between groups. However, at FABS-5+, maintainers had greater overall QOL scores than re-gainers (87.5±10.5 vs 65.4±20.2, P<0.001) and in each QOL sub-domain (P<0.01 all). CONCLUSIONS: Long-term weight outcomes for those who underwent weight-loss surgery were superior to those who did not undergo surgical treatment. While no behavioral factors were identified as predictors of success in long-term weight-loss maintenance, greater QOL was strongly associated with maintenance of weight loss among adolescents who underwent Roux-en-Y gastric bypass surgery surgery.
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Cirurgia Bariátrica/estatística & dados numéricos , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Redução de Peso/fisiologia , Adolescente , Adulto , Dieta/estatística & dados numéricos , Exercício Físico , Feminino , Seguimentos , Humanos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
Phentermine is the most widely prescribed obesity medication in adults, yet studies of its use in the pediatric population are limited. We conducted a retrospective chart review of adolescents with obesity treated in a pediatric weight management clinic to examine the weight loss effectiveness of phentermine added to standard of care (SOC) lifestyle modification therapy versus SOC alone. All patients receiving phentermine plus SOC (n=25) were matched with a comparison group receiving only SOC (n=274). Differences at 1, 3 and 6 months were evaluated using generalized estimated equations adjusting for age, sex and baseline body mass index (BMI) and robust variance standard error estimates for confidence intervals and P-values. Phentermine use was associated with a greater percent change in BMI at 1 month (-1.6%; 95% confidence interval (CI): -2.6, -0.6%; P=0.001), 3 months (-2.9%; 95% CI: -4.5, -1.4%; P<0.001) and 6 months (-4.1%; 95% CI: -7.1, -1.0%; P=0.009) compared with SOC alone, with no differences in systolic or diastolic blood pressure between groups. Heart rate was higher at all time-points in the phentermine plus SOC compared with SOC-only group. These data suggest that short-term use of phentermine added to SOC may enhance weight loss in adolescents with obesity in the clinical setting.
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Fármacos Antiobesidade/uso terapêutico , Obesidade Infantil/prevenção & controle , Fentermina/uso terapêutico , Redução de Peso , Adolescente , Terapia Comportamental , Dieta Redutora , Feminino , Humanos , Masculino , Minnesota/epidemiologia , Obesidade Infantil/terapia , Estudos Retrospectivos , Comportamento de Redução do Risco , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND/OBJECTIVES: Inflammation, oxidative stress and dysregulation of adipokines are thought to be pathophysiological mechanisms linking obesity to the development of insulin resistance and atherosclerosis. In adults, bariatric surgery reduces inflammation and oxidative stress, and beneficially changes the levels of several adipokines, but little is known about the postsurgical changes among adolescents. SUBJECTS/METHODS: In two separate longitudinal cohorts we evaluated change from baseline of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemo-attractant protein-1 (MCP-1), oxidized low-density lipoprotein cholesterol (oxLDL), adiponectin, leptin and resistin up to 12 months following elective laparoscopic Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) surgery in adolescents with severe obesity. RESULTS: In cohort 1, which consisted of 39 adolescents (mean age 16.5±1.6 years; 29 females) undergoing either RYGB or VSG, IL-6 (baseline: 2.3±3.4 pg ml(-1) vs 12 months: 0.8±0.6 pg ml(-1), P<0.01), leptin (baseline: 178±224 ng ml(-1) vs 12 months: 41.4±31.9 ng ml(-1), P<0.001) and oxLDL (baseline: 41.6±11.6 U l(-1) vs 12 months: 35.5±11.1 U l(-1), P=0.001) significantly decreased and adiponectin significantly increased (baseline: 5.4±2.4 µg ml(-1) vs 12 months: 13.5±8.9 µg ml(-1), P<0.001). In cohort 2, which consisted of 13 adolescents (mean age 16.5±1.6 years; 10 females) undergoing RYGB, results were similar: IL-6 (baseline: 1.7±0.9 pg ml(-1) vs 12 months: 0.4±0.9 pg ml(-1), P<0.05) and leptin (baseline: 92.9±31.3 ng ml(-1) vs 12 months: 37.3±33.4 ng ml(-1), P<0.001) significantly decreased and adiponectin significantly increased (baseline: 6.1±2.9 µg ml(-1) vs 12 months: 15.4±8.0 µg ml(-1), P<0.001). When the cohorts were combined to evaluate changes at 12 months, oxLDL also significantly decreased (baseline: 39.8±16.7 U l(-1) vs 12 months: 32.7±11.9 U l(-1), P=0.03). CONCLUSIONS: Bariatric surgery produced robust improvements in markers of inflammation, oxidative stress and several adipokines among adolescents with severe obesity, suggesting potential reductions in risk for type 2 diabetes and cardiovascular disease.
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Adipocinas/sangue , Aterosclerose/etiologia , Derivação Gástrica , Inflamação/etiologia , Obesidade Mórbida/cirurgia , Obesidade Infantil/cirurgia , Redução de Peso , Adiponectina/sangue , Adolescente , Aterosclerose/fisiopatologia , Aterosclerose/prevenção & controle , Biomarcadores/sangue , Feminino , Humanos , Inflamação/fisiopatologia , Inflamação/prevenção & controle , Resistência à Insulina , Interleucina-6/sangue , Lipoproteínas LDL/sangue , Masculino , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/fisiopatologia , Estresse Oxidativo , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Obesidade Infantil/fisiopatologia , Período Pós-Operatório , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Estados Unidos/epidemiologiaRESUMO
Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices with regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to (1) offer a background of the current state of the field of pediatric obesity medicine, (2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials, and (3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial end-point selection, trial duration, implementation of lifestyle modification therapy and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity.
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Fármacos Antiobesidade/uso terapêutico , Obesidade Infantil/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Massa Corporal , Criança , Aconselhamento Diretivo/tendências , Exenatida , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Obesidade Infantil/epidemiologia , Obesidade Infantil/prevenção & controle , Peptídeos/uso terapêutico , Comportamento de Redução do Risco , Peçonhas/uso terapêutico , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: Dynamic oximetry provides a new way to assess the effect of blood storage on the oxygen transport rate (OTR). MATERIALS AND METHODS: In dynamic oximetry, the rate at which oxyhemoglobin becomes deoxyhemoglobin is measured optically, thereby, indirectly measuring the rate at which oxygen leaves the red blood cell (RBC) making it available for transfer to tissues. Extending the physiologic diffusion time in an in vitro apparatus, consisting of a diffusion system and gas exchanger capable of controlling the surface area and the time of exposure for oxygenation and deoxygenation, makes OTR measurement feasible. Eight normal blood donor units, collected in adenine, dextrose, sorbitol, sodium chloride and mannitol , were stored for 8 weeks under standard conditions and serially sampled for OTR. RESULTS: We report that the OTR at the time of blood bank donation appears to be singular for each donor, that the interdonor differences are maintained over time, and that the individual OTR increased 1.72-fold (95% CI 1.51, 1.95) over 8 weeks, adjusting for sex, age and plasma cholesterol level. CONCLUSION: Oxygen transport rate increases during storage; blood units with similar haemoglobin content may have significant differences in OTR. Studies examining blood parameters at the time of donation and blood storage on patient outcomes should consider measuring OTR, as it may contribute to differences in observed efficacy of tissue oxygenation.
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Eritrócitos/metabolismo , Soluções para Preservação de Órgãos/farmacologia , Oximetria/métodos , Oxigênio/sangue , Adenina/farmacologia , Adulto , Câmaras de Exposição Atmosférica , Transporte Biológico , Preservação de Sangue/métodos , Colesterol/sangue , Difusão , Desenho de Equipamento , Eritrócitos/efeitos dos fármacos , Feminino , Glucose/farmacologia , Hemoglobinas/análise , Humanos , Técnicas In Vitro , Masculino , Manitol/farmacologia , Pessoa de Meia-Idade , Oximetria/instrumentação , Oxigênio/administração & dosagem , Oxiemoglobinas/análise , Projetos Piloto , Cloreto de Sódio/farmacologia , Sorbitol/farmacologia , Adulto JovemRESUMO
BACKGROUND: Although obesity affects approximately one in five youths, only a fraction is treated in pediatric weight management clinics. Characteristics distinguishing youth with obesity who seek weight management treatment from those who do not are largely unknown. Yet identification of specific health characteristics which differentiate treatment-seeking from non-treatment seeking youth with obesity may shed light on underlying motivations for pursuing treatment. OBJECTIVES: Compare the cardiometabolic profiles of an obesity treatment-seeking sample of youth to a population-based sample of youth with obesity, while controlling for body mass index (BMI). METHODS: This cross-sectional study included participants, ages 12-17 years, with obesity from the Pediatric Obesity and Weight Evaluation Registry (POWER) and National Health and Nutrition Examination Survey, representing the treatment-seeking and population samples, respectively. Mean differences were calculated for systolic and diastolic blood pressure percentiles, total cholesterol, low-density and high-density lipoprotein-cholesterol, triglycerides, fasting glucose, glycated hemoglobin and alanine aminotransferase, while adjusting for age, sex, race/ethnicity, insurance status, and multiple of the 95th BMI percentile. RESULTS: The POWER and National Health and Nutrition Examination Survey cohorts included 1,823 and 617 participants, respectively. The POWER cohort had higher systolic blood pressure percentile (mean difference 17.4, 95% confidence interval [14.6, 20.1], p < 0.001), diastolic blood pressure percentile (21.8 [19, 24.5], p < 0.001), triglycerides (42.3 [28, 56.5], p < 0.001) and alanine aminotransferase (7.5 [5.1, 9.8], p < 0.001) and lower fasting glucose (-6.9 [-8.2, -5.6], p < 0.001) and high-density lipoprotein-cholesterol (-2.3 [-3.8, -0.9], p < 0.002). There were no differences in total cholesterol or low-density lipoprotein-cholesterol or clinical differences in glycated hemoglobin. CONCLUSION: For a given BMI, obesity treatment-seeking youth are more adversely affected by cardiometabolic risk factors than the general population of youth with obesity. This suggests that treatment-seeking youth may represent a distinct group that is at particularly high risk for the development of future cardiometabolic disease.
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The study purposes were to: (i) Investigate eating behaviours among patients in a paediatric weight management clinical practice and (ii) Compare eating behaviour phenotypes between children with severe obesity and obesity. This was a retrospective cross-sectional study using data collected during clinical encounters. Participants were included if they were 2-12 years old, had a body mass index ≥95th percentile and if a parent or guardian completed the Child Eating Behaviour Questionnaire (CEBQ). Participants (n = 149) were children with severe obesity (n = 108) and obesity (n = 41). The mean Satiety Responsiveness score was significantly lower for children with severe obesity than for children with obesity. Girls with severe obesity had significantly higher Enjoyment of Food and significantly lower Satiety Responsiveness and Slowness in Eating than girls with obesity. The findings demonstrate the potential clinical utility of the CEBQ for informing tailored treatment strategies through identifying eating behaviour phenotypes.
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Comportamento Alimentar , Obesidade Mórbida/psicologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/psicologia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
In two previous, separate clinical trials, we demonstrated significant reductions in body mass index (BMI) with exenatide in adolescents with severe obesity. In the present study, we pooled data from these near identical trials to evaluate factors that may predict BMI reduction at 3 months. Data from 32 patients (mean age 14.3 ± 2.2 years; 69% female; mean BMI 39.8 ± 5.8 kg m(-2)) were included. Exenatide treatment consisted of 5 mcg twice daily for 1 month, followed by an increase to 10 mcg twice daily for 2 additional months. Predictor variables included baseline BMI, BMI percent change at 1 month, incidence of nausea or vomiting and baseline appetite and satiety measures. Treatment effects of percent change in BMI from baseline were estimated within predictor subgroups using generalized estimating equations with exchangeable working correlation and robust variance estimation for confidence intervals and P-values to account for paired observations. The pooled data treatment effect on absolute BMI at 3 months was -3.42% (95% confidence interval: -5.41%, -1.42%) compared to placebo. Within treated participants, appetite at baseline (treatment effect in high [-4.28%] vs. low [1.02%], P = 0.028) and sex (treatment effect in female [-4.78%] vs. male [0.76%], P = 0.007) were significant predictors of change in BMI at 3 months. Baseline BMI, BMI percent change at 1 month, age, incidence of nausea, vomiting, or other gastrointestinal symptoms and satiety scores did not predict 3-month responses. Sex and measures of appetite may serve as useful predictors of glucagon-like peptide-1 receptor agonist treatment response among adolescents with severe obesity.
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Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/administração & dosagem , Obesidade Mórbida/tratamento farmacológico , Peptídeos/administração & dosagem , Peçonhas/administração & dosagem , Adolescente , Índice de Massa Corporal , Criança , Exenatida , Feminino , Humanos , Masculino , Obesidade Mórbida/fisiopatologia , Resultado do Tratamento , Redução de Peso , Adulto JovemRESUMO
The long-term cognitive and functional outcomes of children with mucopolysaccharidosis type I (MPS-IH) post-hematopoietic cell transplant (HCT) are not well documented, and the role of genetic and treatment factors in these outcomes has yet to be defined. In this multi-site, international study, we (1) characterize the cognitive and functional status of 47 individuals (ages 2-25, mean of 10.6 years) with MPS-IH who are 1-24 years post HCT (mean = 9 years) and (2) examine contributions of genotype, transplant characteristics, and sociodemographic factors to cognitive ability, adaptive behavior, and quality of life. The overall cognitive ability of our sample was mildly impaired, more than two standard deviations below general population norms. Parent reported adaptive behaviors (i.e., communication, daily living, and motor skills) were similarly impaired with a relative strength in socialization. Quality of life, as reported by parents, fell more than two standard deviations below population norms for physical functioning; however, psychosocial quality of life (emotional well-being) approximated population norms. In linear regression analysis, adjusted for demographic and treatment factors, mutation severity was associated with lower cognitive ability (p = 0.005) and adaptive functioning (p = 0.004), but not parent ratings of children's quality of life. Older age at HCT was associated with poorer physical quality of life (p = 0.002); lower socioeconomic status (p = 0.028) and unrelated bone marrow HCT (p = 0.010) were associated with poorer psychosocial quality of life. Implications for screening and early intervention for children at risk for poorer cognitive and functional outcomes are described.
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BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest and most severely by the disease. MATERIALS AND METHODS: Fifty-two high-resolution 3T MR imaging datasets were prospectively acquired on 38 subjects with CLN2. A retrospective cohort of 52 disease-free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness. RESULTS: An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, subjects with CLN2 exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemispheres, respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann regions. The second pattern exhibited a difference in thickness from healthy controls but with no discernable change with age (9 left hemispheres, 5 right hemispheres). In the third pattern, there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemispheres, 3 right hemispheres). CONCLUSIONS: This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomic and functional regions that degenerate sooner and more severely than others compared with those in healthy controls may offer targets for directed therapies. The information gained may also provide neurobiologic insights regarding the mechanisms underlying disease progression.
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Encéfalo/patologia , Degeneração Neural/patologia , Lipofuscinoses Ceroides Neuronais/patologia , Criança , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Tripeptidil-Peptidase 1RESUMO
BACKGROUND AND PURPOSE: LINCL is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene that encodes for tripeptidyl peptidase 1, a lysosomal enzyme necessary for the degradation of products of cellular metabolism. With the goal of developing quantitative noninvasive imaging biomarkers sensitive to disease progression, we evaluated a 5-component MR imaging metric and tested its correlation with a clinically derived disease-severity score. MATERIALS AND METHODS: MR imaging parameters were measured across the brain, including quantitative measures of the ADC, FA, nuclear spin-spin relaxation times (T2), volume percentage of CSF (%CSF), and NAA/Cr ratios. Thirty MR imaging datasets were prospectively acquired from 23 subjects with LINCL (2.5-8.4 years of age; 8 male/15 female). Whole-brain histograms were created, and the mode and mean values of the histograms were used to characterize disease severity. RESULTS: Correlation of single MR imaging parameters against the clinical disease-severity scale yielded linear regressions with R2 ranging from 0.25 to 0.70. Combinations of the 5 biomarkers were evaluated by using PCA. The best combination included ADC, %CSF, and NAA/Cr (R2=0.76, P<.001). CONCLUSIONS: The multiparametric disease-severity score obtained from the combination of ADC, %CSF, and NAA/Cr whole-brain MR imaging techniques provided a robust measure of disease severity, which may be useful in clinical therapeutic trials of LINCL in which an objective assessment of therapeutic response is desired.