Defining and identifying predictors of rapid response to pediatric obesity treatment.
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ABSTRACT:
SUBMITTER: Eichen DM
PROVIDER: S-EPMC7202991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA subset of patients with nonalcoholic steatohepatitis (NASH) respond to treatment with vitamin E. The characteristics of responders are not known. The objective of this study was to investigate the outcomes of vitamin E use in clinical practice and to determine factors associated with response to treatment.MethodsA pediatric cohort with NASH treated with vitamin E for 6-24 months was studied retrospectively. Vitamin E response was defined as alanine aminotransferase (ALT) normalization or >50% ALT reduction from baseline. Univariate and multivariate logistic regression was used to determine the predictors of response to vitamin E. Available paired liver biopsy data were analyzed to determine histologic response.ResultsOf the 151 children prescribed vitamin E, 73 met inclusion/exclusion criteria. Of those, 28 (38%) were vitamin E responders. Higher baseline serum alkaline phosphatase (ALP) levels, steatosis grade, and Nonalcoholic Fatty Liver Disease Activity Score (NAS) were associated with response to vitamin E (ALP: odds ratio [OR], 14.1; 95% CI, 1.7-118.6; steatosis: OR 2.5; 95% CI, 1.2-5.0; NAS: OR 1.6; 95% CI, 1.1-2.4). In a multivariate logistic regression model, ALP and steatosis grade rendered an area under the curve of 0.75 (P < .001) for the prediction of response to treatment. Ballooning, NAS, and portal inflammation improved significantly with vitamin E in the subcohort (n = 15) with paired liver biopsies.ConclusionsVitamin E treatment was associated with significant ALT response in 38% of children. Baseline serum ALP levels and steatosis grade were associated with response to treatment.
| S-EPMC7590297 | biostudies-literature
Project description:BackgroundAn agreed-upon definition of treatment response for clinical trials of pediatric acute asthma does not exist, limiting meaningful comparisons among therapeutic interventions and advances in asthma management.ObjectiveTo develop a consensus definition of treatment response for clinical trials of pediatric acute asthma.MethodsA multidisciplinary panel of 22 experts participated in a Web-based modified Delphi process to achieve consensus on a definition of treatment response. Round 1 consisted of closed- and open-ended questions in which panelists ranked measures of treatment response developed by literature review, suggested additional measures, and explained their responses. In rounds 2 and 3, panelists reviewed summary statistics of the panel's rating from prior rounds and reconsidered their rankings. In round 3, pairwise ranking was performed to determine the ranked importance of components. Consensus was defined as 70% or greater agreement among panelists choosing Likert-scale values of 1 to 6 (extremely unimportant to extremely important) and an interquartile range less than 2.ResultsDrawing on results from the expert panel, we developed a definition of treatment response that includes Clinical Severity Score, need for additional therapies, and hospitalization. Clinical Severity Score encompassed most ranked criteria (eg, respiratory distress, wheeze) for a treatment response definition. Panelists recommended that a valid and pragmatic severity score be used consistently across institutions. Panelists also achieved consensus on the top 10 criteria that appropriately classify need for hospitalization.ConclusionsThis consensus definition of treatment response can be used in clinical trials of children with acute asthma to standardize outcome measurement and report meaningful outcomes.
| S-EPMC10164688 | biostudies-literature
Project description:BACKGROUND:In patients with obesity-related hypertension (ORH), reaction to antihypertensive medication is likely influenced by patientcharacteristics. METHODS:Effects of aliskiren, moxonidine and hydrochlorothiazide on 24-h blood pressure (BP) were compared to placebo. Linear mixed effect models were used to analyze the effect of patient characteristics on BP levels and treatment response. RESULTS:Systolic BP response to aliskiren was higher in patients with a BMI >?30.7 kg/m2 compared to patients with a BMI ??30.7 kg/m2 (-21 mmHg versus -4 mmHg). In patients with a hsCRP >?1.8 mg/L the systolic BP response to aliskiren was higher than in patients with a low hsCRP (-15 mmHg versus -7 mmHg). Hydrochlorothiazide (HCTZ) treatment effect on systolic BP was -13 mmHg when heart rate >?71 beats/min compared to -3 mmHg when heart rate was ??71 beats/min. CONCLUSION:In patients with ORH, BP response to aliskiren is positively related to BMI and hsCRP. Systolic BP response to HCTZ is positively related to heart rate and negatively to renin levels. TRIAL REGISTRATION:NCT01138423. Registered June 4th, 2010.
| S-EPMC5654008 | biostudies-literature
Project description:ObjectiveThere is wide variation in the number and types of obesity policies enacted across states, and prior studies suggest that partisan factors may not fully explain this variation. In this exploratory analysis, we examined the association of a broad array of state-level factors with the number and types of obesity policies across states.DesignWe analyzed 32 predictor variables across 7 categories of state-level characteristics. We abstracted data from 1652 state obesity policies introduced during 2009-2014. We used multilevel regression models and principal component analysis to examine the association between state-level characteristics and policy outcomes.Main outcome measuresOur outcome measures included whether bills involved topics that were public health-oriented or business interest-oriented, whether bills were enacted into law, and the number of introduced bills and enacted laws per state.ResultsNumerous state-level characteristics were associated with obesity-related bill introduction and law enactment, and different state characteristics were associated with public health-oriented versus business interest-oriented policies. For example, state-level demographics, economic factors, policy environment, public programs, and the prevalence of obesity's downstream consequences were associated with the number of public health laws whereas obesity prevalence and policy environment were associated with the number of business interest laws.ConclusionsOur results support the hypothesis that a variety of factors contribute to a complex state obesity policymaking environment, highlighting the need for future research to disentangle these key predictors.
| S-EPMC7012724 | biostudies-literature
Project description:This article reviews factors that contribute to excessive weight gain in children and outlines current knowledge regarding approaches for treating pediatric obesity. Most of the known genetic causes of obesity primarily increase energy intake. Genes regulating the leptin signaling pathway are particularly important for human energy homeostasis. Obesity is a chronic disorder that requires long-term strategies for management. The foundation for all treatments for pediatric obesity remains restriction of energy intake with lifestyle modification. There are few long-term studies of pharmacotherapeutic interventions for pediatric obesity. Bariatric surgical approaches are the most efficacious treatment but, because of their potential risks, are reserved for those with the most significant complications of obesity.
| S-EPMC2736391 | biostudies-literature
Project description:This article reviews factors that contribute to excessive weight gain in children and outlines current knowledge regarding approaches for treating pediatric obesity. Most of the known genetic causes of obesity primarily increase energy intake. Genes regulating the leptin signaling pathway are particularly important for human energy homeostasis. Obesity is a chronic disorder that requires long-term strategies for management. The foundation for all treatments for pediatric obesity remains restriction of energy intake with lifestyle modification. There are few long-term studies of pharmacotherapeutic interventions for pediatric obesity. Bariatric surgical approaches are the most efficacious treatment but, because of their potential risks, are reserved for those with the most significant complications of obesity.
| S-EPMC3260452 | biostudies-literature
Project description:The global population has been severely affected by the coronavirus disease 2019 (COVID-19) pandemic, however, with older age identified as a risk factor, children have been underprioritized. This article discusses the factors contributing to the less severe response observed in children following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including, differing viral entry receptor expression and immune responses. It also discusses how emerging and future variants could present a higher risk to children, including those with underlying comorbidities, in developing severe disease. Furthermore, this perspective discusses the differential inflammatory markers between critical and non-critical cases, as well as discussing the types of variants that may be more pathogenic to children. Importantly, this article highlights where more research is urgently required, in order to protect the most vulnerable of our children.
| S-EPMC10248061 | biostudies-literature
Project description:BackgroundUnderlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment.ObjectivesTo present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center.MethodsThis is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients.ResultsThe diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort.ConclusionsTo our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.
| S-EPMC7209105 | biostudies-literature
Project description:ObjectiveRisk of open conversion after endovascular aortic aneurysm repair (EVAR-c) is poorly defined. The purpose of this analysis was to determine outcomes of elective EVAR-c compared with elective primary open abdominal aortic aneurysm repair (PAR) in the Vascular Quality Initiative.MethodsVascular Quality Initiative patients who underwent elective EVAR-c and PAR (2002-2014) were reviewed. Candidate predictors of major adverse cardiac event (MACE) and/or 30-day mortality were entered into a multivariable model, and stepwise elimination was used to reduce the number of covariates to a best subset of predictors. To estimate the additive risk of EVAR-c for MACE or 30-day mortality over PAR, this variable was added along with the best subset of predictors into generalized estimating equations logistic regression models.ResultsWe identified 159 EVAR-c and 3741 PAR patients. EVAR-c patients were older (73.5 ± 8.1 vs 69.5 ± 8.4 years; P < .0001), more likely to have diabetes (21% vs 15%; P = .03), and history of lower extremity bypass (9% vs 4%; P = .0006). EVAR-c was associated with a higher incidence of retroperitoneal aortic exposure (41%; n = 64 vs PAR, 26%, n = 976; P < .0001), use of a bifurcated graft (65%; n = 101 vs PAR, 52%; n = 1923; P = .001), greater blood loss (median [interquartile range], 2000 mL [1010-3500] vs PAR, 1200 mL [750-2000]; P < .0001) and longer procedure times (EVAR-c, 275 ± 122 minutes vs PAR, 232 ± 9 minutes; P < .0001). However, PAR more frequently was completed with a suprarenal and/or mesenteric cross-clamp (74%, n = 2749 vs EVAR-c, 53%, n = 83; P < .0001) and had a higher incidence of concomitant procedures (26%; n = 972 vs EVAR-c, 18%; n = 28; P = .03). Nonadjusted 30-day mortality was greater after EVAR-c: EVAR-c, 8% (n = 10) vs PAR, 3% (n = 105); P = .009. There was no difference in complication rates: EVAR-c, 33% (n = 52) vs PAR, 28% (n = 1056); P =.3. Preoperative 30-day mortality predictors included age (odds ratio [OR], 1.06/y, 95% confidence interval [CI], 1.04-1.1; P < .0001), chronic obstructive pulmonary disease (OR, 2.4; 95% CI, 1.6-3.5; P < .0001), history of leg bypass (OR, 2.3, 1.2-4.4;P =.01), suprarenal cross-clamp (OR 2.2, 1.2-4.1;P =.01), prior carotid revascularization (OR 2.2; 95% CI, 1.3-3.8; P = .0004), congestive heart failure (OR, 1.8; 95% CI, 0.9-3.5; P = .08), and female sex (OR, 1.6; 95% CI, 1.1-2.3; P = .02; area under the curve, 0.75). When controlling for covariates, EVAR-c was not significantly associated with MACE (OR, 1.2; 95% CI, 0.7-2.0; P = .4) or 30-day mortality (OR, 2.0; 0.9-4.2; P = .08).ConclusionsEVAR-c patients are typically older, have more comorbidities, and experience greater blood loss and longer procedure times compared with PAR patients. However, postoperative morbidity and mortality are primarily driven by patient covariates and intraoperative factors, rather than the need for endograft explantation. Several preoperative variables were identified as predictors of 30-day mortality after elective EVAR-c and should be considered during the decision-making process for remedial treatment of failed endovascular PAR.
| S-EPMC4808623 | biostudies-literature
Project description:BackgroundAdolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard-of-care treatments (psychotherapy and medication), roughly one third will not.MethodsHere, we have reviewed the literature in order to discuss the concept of treatment-resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials.ResultsWe propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first- and second-line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence-based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted.ConclusionsAs evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.
| S-EPMC8314167 | biostudies-literature