Treatment Of Pediatric Obesity Research Articles

Medical treatment of pediatric obesity

Background: The increasing prevalence of pediatric obesity over the past few decades has become a serious public health concern. Quarantine measures during the coronavirus disease pandemic have led to an increase in childhood obesity rates. Children with obesity are at greater risk for type 2 diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, obstructive sleep apnea, and adult obesity. Lifestyle modification therapy is the firstline treatment for pediatric obesity. Pharmacotherapy is the next logical treatment option in patients in whom lifestyle modifications alone are ineffective.Current Concepts: Anti-obesity medications for pediatric obesity include metformin, orlistat, glucagon-like peptide-1 agonists, phentermine, and phentermine/topiramate combination. Metformin, a medication used for type 2 diabetes has not been approved for treatment of pediatric obesity. Orlistat, a lipase inhibitor, prevents fat absorption from the human diet. Liraglutide, a glucagon-like peptide-1 agonist, is associated with decreased gastric emptying, increased satiety, and appetite suppression. Phentermine, a norepinephrine reuptake inhibitor, is approved by the Food and Drug Administration for short-term treatment of patients aged >16 years. Phentermine/topiramate is a combination of the conventional anti-obesity medication, phentermine and an antiepileptic agent, topiramate that is commonly associated with weight loss as an adverse effect.Discussion and Conclusion: Anti-obesity treatment may serve as the next logical therapeutic option for pediatric obesity. However, sufficient lifestyle modification therapy should be attempted before considering medication, and anti-obesity medications should preferably be used in combination with lifestyle modifications. Monitoring growth and pubertal development during anti-obesity treatment is essential to ensure healthy development of children and adolescents.

Families Benefit After Utilization of a Clinic-Based Food Pantry Irrespective of Food Insecurity Experiences in a Pediatric Obesity Treatment Program.

To evaluate the congruence between food insecurity screening outcome and clinic-based food pantry utilization and to examine caregiver reported comfort, motivation, and benefits of utilization. Mixed-methods study. Academic pediatric obesity treatment clinic. Convenience sample of caregivers. Clinic-based food pantry offered irrespective of food insecurity screening outcome. Food insecurity screening (Hunger Vital Sign) and severity, self-rated caregiver health, willingness to disclose food insecurity and receive food, and food-related stress. Chi-square and t-tests were utilized to examine associations and descriptive analysis explored benefits. Rapid qualitative analysis was utilized to identify themes. Caregivers of 120 children were included (child mean age 11.8; 56.7% female, 67.6% Non-Hispanic Black), with 47 of 59 eligible completing follow-up surveys and 14 completing in-depth interviews. Approximately half (N = 30/59, 50.8%) of families utilizing the food pantry screened negative for food insecurity. Families utilizing the food pantry were more likely to report severe food insecurity (N = 23/59; 38.9%) compared to those declining (N = 3/61; 4.9%, P < .001). Caregivers accepting food were able to meet a child health goal (N = 30/47, 63.8%). Caregivers reported feeling comfortable receiving food (N = 13/14) and felt utilizing the food pantry led to consumption of healthier foods (N = 7/14). Families who screened both positive and negative for food insecurity utilized and benefited from a clinic-based food pantry. Clinics should consider strategies offering food resources to all families irrespective of screening outcome.

Cost-effectiveness analysis of individual-level obesity treatment in paediatrics: A scoping review.

This scoping review informs a health economics perspective on the treatment of paediatric obesity. The results detail recently published research findings on the cost-effectiveness of paediatric obesity treatments and identify key characteristics of cost-effective interventions. A structured search was applied to six databases with no data restriction through March 2023: Medline, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO. Studies that included a cost analysis of an individual level, weight management intervention (behavioural, pharmacotherapy, and surgical) in youth, with obesity, ages 2 to 21 years were eligible for inclusion. Of the 4371 records identified in the initial search, 353 underwent full-text review, 39 studies met the pre-specified inclusion criteria. The majority were published after 2010 (n = 36/39, 92%) and applied to high-income countries (n = 39/39, 100%). Thirty-five of the studies assessed the cost-effectiveness of lifestyle interventions (90%), and four studies assessed surgical outcomes (10%). No pharmacotherapy studies met eligibility criteria. Although the outcome measures differed across the studies, all four surgical interventions were reported to be cost-effective. Thirty of the 35 (85%) lifestyle modification studies were reported to be cost-effective compared to the study comparator examined. There is a small amount of evidence that individual-level paediatric obesity treatment interventions are cost-effective and, in some cases cost-saving, with most of this work conducted on behavioural interventions. The economic evaluation of paediatric obesity interventions poses various methodologic challenges, which should be addressed in future research to fully use the potential of economic evaluation as an aid to decision-making.

The psychosocial functioning in adolescents with severe obesity evaluated throughout the strengths and difficulties questionnaire (SDQ): a preliminary report.

Childhood obesity is associated with poor psychological adjustment. Severely impacts the psychological adjustment of young patients. To assess the psychological functioning of children and adolescents, several questionnaires have been proposed so far. Although the Strengths and Difficulties Questionnaire (SDQ) is one of the most well-used tools, its application in obesity research is scarce. The study is aimed at assessing the psychological profile of a sample of Italian children and adolescents seeking an in-hospital multidisciplinary body weight reduction program for obesity, via SDQ. One hundred and fourteen consecutive Italian children and adolescents with obesity (43 males/71 females, age range: 11-17 years, mean age ± SD: 15.1 ± 1.66, body mass index-BMI ± SD: 37.4 ± 6.13 kg/m2), were recruited at the Division of Auxology, Istituto Auxologico Italiano IRCCS, Piancavallo (VB). Obese Females reported worse conditions of emotional symptoms (t = 5.48; p < 0.001) and peer problems (t = 2.34; p = 0.021), as well as higher which were associated with greater scores of pro-social behaviors than obese males (t = 3.07; p = 0.003). The total difficulties score (t = 4.00; p < 0.001) and the total impact score (t = 4.53; p < 0.001) were significantly higher in females than males. No statistically significant differences in SDQ variables were found in relation to the degree of obesity (BMI SDS: 2-2.99; BMI SDS: > 3). These findings can contribute to understand the psychological condition of adolescents with obesity in a better way and also to develop effective interventions for the treatment of pediatric obesity which not only take into account the medical and physical aspects but also the emotional and social difficulties expressed by adolescents with obesity.

A scoping review of physical activity-based interventions for obesity management in children and adolescents during the COVID-19 pandemic.

Overweight and obesity have emerged as global health issues among children and adolescents. Restrictions related to the COVID-19 pandemic have aggravated the threat of paediatric obesity due to the prevalent reduction in physical activity (PA) in children and adolescents. However, this has also created an opportunity for healthcare professionals to explore new strategies to address this persistent problem. A systematically conducted scoping review was performed on 15 online databases to summarise and analyse the design, efficacy, and feasibility of PA-based weight management interventions for children and adolescents during the pandemic. Finally, we reviewed 23 eligible studies that were published between 2021 and 2023. The included interventions were presented to 1938 children and adolescents and 355 parents using a virtual or virtually blended face-to-face approach during the pandemic. The intervention design included a basic PA programme with three optional components (nutritional education, sociopsychological counselling, and medication consultations). Implementation generally resulted in favourable changes in body mass index (BMI) and/or body size or composition (primary outcomes), as well as health behaviours, physical health or fitness, and individual well-being (secondary outcomes). A longer duration of exposure to the intervention, female sex, and older age were associated with a higher efficacy of the included interventions. Moreover, the interventions showed high feasibility, with medium-high participant attendance, high acceptance/satisfaction in both children and adolescents and their parents and teachers, and strong participant engagement. This may be related to the high accessibility of health information, timely social support, and enhanced self-efficacy. In conclusion, both the virtual and blended delivery of well-planned weight management interventions during the pandemic show promise for the treatment and control of paediatric obesity. The lessons learned from the pandemic may help improve the design of future interventions and inform the proper integration of new technologies that have emerged in the post-pandemic world.

Applications of artificial intelligence in the management of childhood obesity.

Childhood obesity has emerged as a significant public health challenge, with long-term implications that often extend into adulthood, increasing the susceptibility to chronic health conditions. The objective of this review is to elucidate the applications of artificial intelligence (AI) in the prevention and treatment of pediatric obesity, emphasizing its potential to complement and enhance traditional management methods. We undertook a comprehensive examination of existing literature to understand the integration of machine learning and other AI techniques in childhood obesity management strategies. The findings from numerous studies suggest a strong endorsement for AI's role in addressing childhood obesity. Particularly, machine learning techniques have shown considerable efficacy in augmenting current therapeutic and preventive approaches. The intersection of AI with conventional obesity management practices presents a novel and promising approach to fortify interventions targeting pediatric obesity. This review accentuates the transformative capacity of AI, thereby advocating for continued research and innovation in this rapidly evolving domain.

Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control.

GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat adolescent obesity. However, the effect on endogenous GLP-1 secretory patterns following treatment in adolescents is unknown. The GLP-1RA exenatide was shown to significantly lower BMI and 2-hour glucose in adolescents with obesity, in the placebo-controlled, randomized controlled trial Combat-JUDO. The aim of this study was to evaluate effects of weekly injections of 2 mg exenatide extended release on secretory patterns of endogenous hormones during OGTT. This study was a pre-planned sub-study of the Combat-JUDO trial, set at the Pediatric clinic at Uppsala University Hospital, Sweden and Paracelsus Medical University, Austria. 44 adolescents with obesity were included and randomized 1:1 to treatment:placebo. 19 patients in the treatment group and 18 in the placebo group completed the trial. Before and after treatment, GLP-1, glucose, insulin, glucagon and glicentin levels were measured during OGTT; DPP-4 and proinsulin were measured at fasting. A per-protocol approach was used in the analyses. Exenatide treatment did not affect GLP-1 levels during OGTT. Treatment significantly lowered DPP-4, proinsulin and the proinsulin-to-insulin ratio at fasting, increased glicentin levels but did not affect insulin, C-peptide or glucagon levels during OGTT. Weekly s.c. injections with 2 mg of exenatide maintains endogenous total GLP-1 levels and lowers circulating DPP-4 levels. This adds an argument in favor of using exenatide in the treatment of pediatric obesity. clinicaltrials.gov, identifier NCT02794402.

The Use of Electronic Health Record Data to Identify Variation in Referral, Consent, and Engagement in a Pediatric Intervention for Overweight and Obesity: A Cross-Sectional Study.

Clinical weight management programs face low participation. The authors assessed whether using electronic health record (EHR) data can identify variation in referral, consent, and engagement in a pediatric overweight and obesity (OW/OB) intervention. Using Epic EHR data collected between August 2020 and April 2021, sociodemographic and clinical diagnostic data (ie, International Classification of Disease [ICD] codes from visit and problem list [PL]) were analyzed to determine their association with referral, consent, and engagement in an OW/OB intervention. Bivariate analyses and multivariable logistic regression modeling were performed, with Bayesian inclusion criterion score used for model selection. Compared with the 581 eligible patients, referred patients were more likely to be boys (60% vs. 54%, respectively; P = 0.04) and have a higher %BMIp95 (119% vs. 112%, respectively; P < 0.01); consented patients were more likely to have a higher %BMIp95 (120% vs. 112%, respectively; P < 0.01) and speak Spanish (71% vs. 59%, respectively; P = 0.02); and engaged patients were more likely to have a higher %BMIp95 (117% vs. 112%, respectively; P = 0.03) and speak Spanish (78% vs. 59%, respectively; P < 0.01). The regression model without either ICD codes or PL diagnoses was the best fit across all outcomes, which were associated with baseline %BMIp95 and health clinic location. Neither visit nor PL diagnoses helped to identify variation in referral, consent, and engagement in a pediatric OW/OB intervention, and their role in understanding participation in such interventions remains unclear. However, additional efforts are needed to refer and engage younger girls with less extreme cases of OW/OB, and to support non-Hispanic families to consent.

Attrition rate and predictors of a monitoring mHealth application in adolescents with obesity.

Integrating mobile health (mHealth) into paediatric obesity treatment can provide opportunities for more personalized and lifetime treatment. However, high attrition rates pose a significant challenge. The current study attempts to better understand attrition by exploring (1) attrition rates of a monitoring mHealth application for usage over 14 days and (2) testing predictors of attrition in adolescents with obesity. Participants were 69 adolescents between 12 and 16 years old who engaged in a multidisciplinary obesity treatment centre (either outpatient or inpatient) in two countries (Belgium and France). To assess the attrition rates, frequency distributions were used. To test the predictors of attrition, zero-inflated negative binomial regression was performed. Attrition rates were high, in the outpatient group, more than half of the participants (53.3%) used the app for only 0-7 days. In the inpatient group, this percentage was 24.1%. Only deficits in initiating (a component of executive functions) were a negative predictor of attrition, indicating that deficits in initiating lead to lower attrition rates. This study provides evidence for high attrition rates in mHealth interventions for adolescents with obesity and was the first to investigate psychological predictors of attrition to an mHealth monitoring tool in adolescents with obesity in treatment. Findings regarding predictors of attrition should be approached with caution due to the small sample size.

Overlooked Outcomes in Pediatric Obesity Management—Unintended Consequences

This Viewpoint describes unintended consequences of pediatric obesity treatment plans and the need for evidence balancing potential benefits vs harms of these plans.

A Narrative Review: Phentermine and Topiramate for the Treatment of Pediatric Obesity.

The prevalence of pediatric obesity has increased exponentially over the past four decades. The American Academy of Pediatrics recently released updated clinical practice guidelines highlighting the importance of identifying pediatric obesity as a chronic disease. The guidelines support consideration of concurrent treatment with intensive lifestyle interventions, obesity pharmacotherapy, and bariatric surgery. The dramatic rise in pediatric obesity has spurred interest in utilizing obesity pharmacotherapy to support sustained weight reduction in pediatric cohorts, in the hopes of preventing the emergence of later-appearing, significant co-morbidities. Despite the enormous demand, the obstacles posed by performance of needed clinical trials in the pediatric population markedly limits available pharmacotherapy for the treatment of obesity in pediatrics. Currently, there are five medications approved by the Food and Drug Administration for use in youth with obesity. In 2022, the phentermine/topiramate (PHEN/TPM), once-daily, controlled-release, combination product received FDA approval, for the indication of chronic weight management, in youth with obesity, ages 12 years and older. The objectives of this narrative review are to: (1) Review the mechanism of action of phentermine and topiramate, (2) Summarize the safety and efficacy data of topiramate and phentermine use as both monotherapies and in combination, and (3) Discuss clinical practice guidelines and clinical implications, for the use of these agents in youths with obesity.

Updates in the Treatment of Pediatric Obesity

Updates in the Treatment of Pediatric Obesity

A Multidisciplinary Approach to Pediatric Obesity Shows Improvement Postintervention.

Outpatient management of pediatric obesity can be difficult, requiring a significant time commitment from both provider and patient. Multidisciplinary clinic-based programs have shown promising effects in reducing BMI during intervention, but whether these changes are sustained over time is not well studied. The purpose of this study was to determine the post-treatment outcomes of children seen in a multidisciplinary pediatric obesity clinic (MPOC). A retrospective chart review was performed using the MPOC database, which included all clinic patients from January 2008 to August 2016 who attended a minimum of 2 visits (n=472). The primary outcome was the absolute change in BMI Z-score (BMIZ) from the final intervention visit compared to 1- and 2-years post-intervention. Multivariate regression analysis was performed to characterize predictors of change in BMIZ. MPOC patients ranged in age from 3 to 18 years. Mean BMIZ decreased significantly during intervention (-0.13 ± 1.47, P < .001) and was maintained at 1- and 2-years post-intervention. In participants ages 3 to 5, BMIZ further decreased at 1 year post intervention (-0.27 ± 0.26, P < .001). Age at time of referral was the only significant predictor of change in BMIZ. Outpatient, multidisciplinary intervention for pediatric obesity was effective in reducing or stabilizing BMIZ during and beyond the intervention, particularly when patients were referred at an early age. Although primary prevention is the ideal management, multidisciplinary clinic intervention can be effective in the sustained treatment of pediatric obesity.

Current and future pharmacotherapies for obesity in children and adolescents.

Obesity is a common chronic disease in children and adolescents and its prevalence is increasing worldwide. The causes are multifactorial but involve biological predisposition towards a specific body-weight set point and defended adipose tissue mass converging with an obesogenic environment. Comprehensive treatment of paediatric obesity includes lifestyle modification therapy, anti-obesity medications (AOMs) and/or metabolic surgery. Lifestyle modification therapy used alone produces fairly modest weight loss for most youth with obesity. The emergence of new AOMs has changed the landscape of paediatric weight management, improving the outlook for youth with obesity. This Review briefly highlights obesity development pathways in youth and the role that pharmacotherapy can play in counteracting these pathophysiological forces. Here, results from adolescent AOM clinical trials published since 2020 are reviewed, including the safety, efficacy and tolerability of the newest treatments (glucagon-like peptide 1 receptor agonists and phentermine-topiramate). The importance of a comprehensive and chronic care model, including both lifestyle modification and ongoing pharmacotherapy, will be discussed in the context of maximizing long-term health outcomes. Finally, insight will be provided into the emerging pipeline of AOMs (for example, incretin receptor co-agonists and tri-agonists) and how future therapies might fundamentally change the prognosis for youth with obesity.

Recruitment and reach in a school-based pediatric obesity intervention trial in rural areas.

The purpose of this study is to evaluate two recruitment strategies on schools and participant participation rates and representativeness (reach) within a pediatric obesity treatment trial tailored for families who live in rural areas. Recruitment of schools was evaluated based on their progress toward enrolling participants. Recruitment and reach of participants were evaluated using (1) participation rates and (2) representativeness of demographics and weight status of participants compared to eligible participants (who did not consent and enroll) and all students (regardless of eligibility). School recruitment, as well as participant recruitment and reach, were evaluated across recruitment methods comparing opt-in (i.e., caregivers agreed to allow their child to be screened for eligibility) vs. screen-first (i.e., all children screened for eligibility). Of the 395 schools contacted, 34 schools (8.6%) expressed initial interest; of these, 27 (79%) proceeded to recruit participants, and 18 (53%) ultimately participated in the program. Of schools who initiated recruitment, 75% of schools using the opt-in method and 60% of schools using the screen-first method continued participation and were able to recruit a sufficient number of participants. The average participation rate (number of enrolled individuals divided by those who were eligible) from all 18 schools was 21.6%. This percentage was higher in schools using the screen-first method (average of 29.7%) compared to schools using the opt-in method (13.5%). Study participants were representative of the student population based on sex (female), race (White), and eligibility for free and reduced-price lunch. Study participants had higher body mass index (BMI) metrics (BMI, BMIz, and BMI%) than eligible non-participants. Schools using the opt-in recruitment were more likely to enroll at least 5 families and administer the intervention. However, the participation rate was higher in screen-first schools. The overall study sample was representative of the school demographics.

Can prebiotics help tackle the childhood obesity epidemic?

Globally, excess weight during childhood and adolescence has become a public health crisis with limited treatment options. Emerging evidence suggesting the involvement of gut microbial dysbiosis in obesity instills hope that targeting the gut microbiota could help prevent or treat obesity. In pre-clinical models and adults, prebiotic consumption has been shown to reduce adiposity partially via restoring symbiosis. However, there is a dearth of clinical research into its potential metabolic benefits in the pediatric population. Here, we provide a succinct overview of the common characteristics of the gut microbiota in childhood obesity and mechanisms of action of prebiotics conferring metabolic benefits. We then summarize available clinical trials in children with overweight or obesity investigating the effects of prebiotics on weight management. This review highlights several controversial aspects in the microbiota-dependent mechanisms by which prebiotics are thought to affect host metabolism that warrant future investigation in order to design efficacious interventions for pediatric obesity.

Improving Health Behaviors and Weight Parameters With Motivational Interviewing and the TEEEN Program in an Ethnically and Socioeconomically Diverse Pediatric Population

ObjectiveObesity affects 14.7 million children and adolescents in the United States. Children's health behaviors are affected by parental health practices. Therefore, pediatric obesity interventions should include parents. The objective of this study was to assess the changes in self-reported health behaviors in a diverse population attending the TEEEN program, with motivational interviewing of child-parent dyads as a key component, for 1 year. MethodsHere we assessed the changes in Family and Nutrition and Physical Activity (FNPA) screening tool scores, a tool that assesses obesogenic behaviors, in the context of MI of child-parent dyads in a racially, ethnically, and socioeconomically diverse population who attended the TEEEN (Teens, Empowerment, Education, Exercise, Nutrition) program, a nonclinic and family-based behavior program in Massachusetts, for 1 year. ResultsParticipation in the TEEEN program, which includes MI of child-parent dyads, was associated with a significant increase in the overall FNPA score (median change= 4 points, P = .007). We observed that 76.5% of children experienced a decrease in BMI% and BMI z-score. The change in BMI% (median= −0.9, P = .006) and change in BMI z-score (median= −0.2, P = .008) were statistically significant. ConclusionParticipation in the TEEEN program seemed to be beneficial based on aspects of the FNPA screening tool and changes in weight parameters. The FNPA screening tool enhanced-motivational interviewing of child-parent dyads shows promise as an approach to address obesogenic behaviors. This study provides a detailed framework for medical providers to address pediatric obesity in a nonclinic setting with less time constraints.

Authors’ Response: Treatment of Pediatric Overweight and Obesity: Position of the Academy of Nutrition and Dietetics Based on Systematic Reviews

Authors’ Response: Treatment of Pediatric Overweight and Obesity: Position of the Academy of Nutrition and Dietetics Based on Systematic Reviews

Translating knowledge into action for child obesity treatment in partnership with Parks and Recreation: study protocol for a hybrid type II trial

BackgroundSafe and effective treatment exists for childhood obesity, but treatment recommendations have largely not been translated into practice, particularly among racial and ethnic minorities and low-wealth populations. A key gap is meeting the recommended treatment of ≥26 h of lifestyle modification over 6–12 months. Fit Together is an effective treatment model that meets these recommendations by integrating healthcare and community resources. Pediatric providers screen children for obesity, deliver counseling, and treat co-morbidities, while Parks and Recreation partners provide recreation space for a community nutrition and physical activity program.MethodsThis study will use a hybrid type II implementation-effectiveness design to evaluate the effectiveness of an online implementation platform (the Playbook) for delivering Fit Together. Clinical and community partners in two North Carolina communities will implement Fit Together, using the Playbook, an implementation package designed to facilitate new partnerships, guide training activities, and provide curricular materials needed to implement Fit Together. An interrupted time series design anchored in the Process Redesign Framework will be used to evaluate implementation and effectiveness outcomes in intervention sites. Implementation measures include semi-structured interviews with partners, before and after the implementation of Fit Together, and quantitative measures assessing several constructs within the Process Redesign Framework. The participants will be children 6–11 years old with obesity and their families (n=400). Effectiveness outcomes include a change in child body mass index and physical activity from baseline to 6 and 12 months, as compared with children receiving usual care. Findings will be used to inform the design of a dissemination strategy guided by the PCORI Dissemination Framework.DiscussionThis project addresses the knowledge-to-action gap by developing evidence-based implementation tools that allow clinicians and communities to deliver effective pediatric obesity treatment recommendations. Future dissemination of these tools will allow more children who have obesity and their families to have access to effective, evidence-based care in diverse communities.Trial registrationClinicalTrials.gov identifier: NCT05455190. Registered on 13 July 2022

Usability and Satisfaction Outcomes from a Pilot Open Trial Examining Remote Patient Monitoring to Treat Pediatric Obesity during the COVID-19 Pandemic.

Pediatric obesity is common and a significant burden. Supplementing pediatric obesity treatment with technology is needed. This manuscript examines the usability and satisfaction, as well as explores initial effectiveness, of a remote patient monitoring system (RPMS) designed for youth presenting for pediatric weight management treatment. 47 youth, 10 to 17 years old, with obesity and a caregiver participated. For three months, families received treatment via the RPMS. Usability and satisfaction outcomes were examined. Exploratory analyses were conducted to examine initial effectiveness from baseline and post-treatment (month 3) assessments. More than 80% of patients used the RPMS, and overall, patients completed 27 out of 90 daily sessions (30%). Youth and caregivers reported high satisfaction. Non-parametric tests revealed no significant improvements for youth or caregiver weight status after the RPMS treatment. Significant improvements in other outcomes examined were limited. Families were satisfied with the RPMS, but use of the system was limited. Initial effectiveness was not able to be determined due to the amount of missing data, which was impacted by the COVID-19 pandemic. Modifications of the RPMS and future evaluation of usability and effectiveness are warranted to determine utility in supplementing pediatric obesity clinical treatment.