Correction: Exploring the Effect of the Dynamics of Behavioral Phenotypes on Health Outcomes in an mHealth Intervention for Childhood Obesity: Longitudinal Observational Study.

[This corrects the article DOI: 10.2196/45407.].

Exploring the Effect of the Dynamics of Behavioral Phenotypes on Health Outcomes in an mHealth Intervention for Childhood Obesity: Longitudinal Observational Study.

BACKGROUND: Advancements in mobile health technologies and machine learning approaches have expanded the framework of behavioral phenotypes in obesity treatment to explore the dynamics of temporal changes. OBJECTIVE: This study aimed to investigate the dynamics of behavioral changes during obesity intervention and identify behavioral phenotypes associated with weight change using a hybrid machine learning approach. METHODS: In total, 88 children and adolescents (ages 8-16 years; 62/88, 71% male) with age- and sex-specific BMI ≥85th percentile participated in the study. Behavioral phenotypes were identified using a hybrid 2-stage procedure based on the temporal dynamics of adherence to the 5 behavioral goals during the intervention. Functional principal component analysis was used to determine behavioral phenotypes by extracting principal component factors from the functional data of each participant. Elastic net regression was used to investigate the association between behavioral phenotypes and weight change. RESULTS: Functional principal component analysis identified 2 distinctive behavioral phenotypes, which were named the high or low adherence level and late or early behavior change. The first phenotype explained 47% to 69% of each factor, whereas the second phenotype explained 11% to 17% of the total behavioral dynamics. High or low adherence level was associated with weight change for adherence to screen time (ß=-.0766, 95% CI -.1245 to -.0312), fruit and vegetable intake (ß=.1770, 95% CI .0642-.2561), exercise (ß=-.0711, 95% CI -.0892 to -.0363), drinking water (ß=-.0203, 95% CI -.0218 to -.0123), and sleep duration. Late or early behavioral changes were significantly associated with weight loss for changes in screen time (ß=.0440, 95% CI .0186-.0550), fruit and vegetable intake (ß=-.1177, 95% CI -.1441 to -.0680), and sleep duration (ß=-.0991, 95% CI -.1254 to -.0597). CONCLUSIONS: Overall level of adherence, or the high or low adherence level, and a gradual improvement or deterioration in health-related behaviors, or the late or early behavior change, were differently associated with weight loss for distinctive obesity-related lifestyle behaviors. A large proportion of health-related behaviors remained stable throughout the intervention, which indicates that health care professionals should closely monitor changes made during the early stages of the intervention. TRIAL REGISTRATION: Clinical Research Information Science KCT0004137; https://tinyurl.com/ytxr83ay.

Parent and child characteristics associated with treatment non-response to a short- versus long-term lifestyle intervention in pediatric obesity.

BACKGROUND/OBJECTIVES: This study aimed to identify the factors associated with short- or long-term non-response to an obesity intervention in children and adolescents. SUBJECTS/METHODS: In this observational study, a total of 242 children and adolescents (sex- and age-specific body mass index (BMI) ≥ 85th percentile) were divided into three groups according to the BMI z-score change after 6 (n = 163) and 24 months (n = 110) of participating in an obesity intervention: responders, low responders, and non-responders if the BMI z-score decrease was ≥0.25, 0 to 0.25, and if it increased, respectively. RESULTS: Short-term non-response was associated with higher maternal psychosocial stress (OR = 2.34, 95% CI [1.07-5.11]) and adolescence (>11 years; OR = 2.40, 95% CI [1.10-5.22]). The odds of long-term non-response were reduced by an increased vegetable consumption of more than five dishes per week (OR = 0.21, 95% CI [0.07-0.69]) and an hour of increased sleep duration during weekends (OR = 0.14, 95% CI [0.04-0.53]). CONCLUSIONS: Short-term non-response was associated with child and maternal characteristics, whereas long-term non-response was associated with actual lifestyle changes such as sleep duration and vegetable consumption. Children with obesity may benefit from an hour of weekend catch-up sleep in lowering the risk of long-term treatment non-response. An individualized approach should be considered for children of older age and mothers with a higher level of stress, as they may not benefit from a conventional short-term lifestyle intervention.

Clinical and genetic analyses of patients with lateralized overgrowth.

BACKGROUND: The genetic features and treatment strategies of lateralized overgrowth have been elusive. We performed this study to analyze the genetic characteristics and treatment results of propranolol- or alpelisib-treated patients with lateralized overgrowth. METHODS: Fifteen patients with lateralized overgrowth were involved. Clinical characteristics and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Targeted exome sequencing with a gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and treatment results were evaluated. The PIK3CA inhibitor alpelisib was prescribed via a managed access program. RESULTS: The identified mutations were PIK3CA (n = 7), KRAS (n = 2), PTEN (n = 1), MAP2K3 (n = 1), GNAQ (n = 1), TBC1D4 (n = 1), and TEK (n = 1). Propranolol was prescribed in 12 patients, and 7 experienced mild improvement of symptoms. Alpelisib was prescribed in two patients with a PIK3CA mutation, and the reduction of proliferated masses after 1 year of treatment was proved by WB-MRI. CONCLUSIONS: Targeted exome sequencing identified various genetic features of lateralized overgrowth. Propranolol could be applied as an adjuvant therapy for reducing vascular symptoms, but a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.

Factors associated with the perception of parents and children regarding obesity-related terminology used by healthcare professionals in a sample of Korean children and adolescents with obesity.

OBJECTIVE: This study aimed to compare how children with overweight or obesity and their parents perceive the obesity-related terms used by healthcare professionals and investigate the factors associated with these perceptions. METHODS: Children and adolescents aged 8-16 years with overweight or obesity (n = 192) and their parents participated in the cross-sectional study by responding to a 5-point Likert-scale questionnaire on 10 obesity-related terms, including "chubby," "weight problem," "weight," "overweight," "BMI," "obese," "heavy," "fleshy," "fat," and "severely obese." RESULTS: For both children and parents, "chubby" was the most desirable term (mean ± standard deviation: 3.50 ± 1.12 and 2.95 ± 0.83, respectively), and "severely obese" was the least acceptable term (2.83 ± 1.17 and 2.02 ± 1.02, respectively). Although the parents preferred all the terms less than the children did (p < 0.001), "weight problem" was considered most motivating for a child to lose weight (3.93 ± 0.94). Among children, older age and a larger self-perceived body size were associated with a more positive response towards obesity-related terms, whereas having internalized or externalized problems were negatively associated with these terms. Parents with a history of cardiovascular disease considered "severely obese" (ß = -0.419, [95% CI: -0.739, -0.099]) and "fat" (ß = -0.457, [95% CI: -0.750, -0.164]) less desirable. CONCLUSIONS: Children and adolescents had a higher preference for obesity-related terms than their parents and preferred that healthcare professionals use euphemistic terms such as "chubby," or neutral terms such as "weight problem." Children with larger self-perceived body sizes or older age had a higher preference for obesity-related words. The terms used by healthcare professionals to describe excess weight must be motivating and respectful for all family members participating in the treatment.

Evaluation of users' level of satisfaction for an artificial intelligence-based diagnostic program in pediatric rare genetic diseases.

The artificial intelligence (AI)-based genetic diagnostic program has been applied to genome sequencing to facilitate the diagnostic process. The objective of the current study was to evaluate the experience and level of satisfaction of participants using an AI-based diagnostic program for rare pediatric genetic diseases. The patients with neurodevelopmental disorders or hearing impairments, their guardians, and their physicians from 16 tertiary general hospitals were enrolled. The study period was from April 2020 to March 2021. A survey was designed to assess their experience and level of satisfaction. A total of 30 physicians and 243 patients and guardians (199 neurodevelopmental disorders and 44 hearing impairments) completed the survey. DNA samples of the subjects were collected through buccal swabs or blood collection: 211 subjects (86.8%) through buccal swab and 29 subjects (11.9%) through blood collection. Average turnaround time for result receipt was 57.54 ± 32.42 days. For the sampling method, 193 patients and guardians (81.1%) and 28 physicians (93.3%) preferred buccal swab. The level of satisfaction of the 2 groups participating in the AI-based diagnostic program was 8.31 ± 1.71 out of 10 in the patient and guardian group and 8.42 ± 1.23 in the physician group. Clinicians, patients, and guardians are satisfied with the AI-based diagnostic program in general. With an increase in AI-based precision medicine solutions, the evaluation of the user's satisfaction with appropriate provision will help improve personal health care.

Sedentary Time and Fast-Food Consumption Associated With Weight Gain During COVID-19 Lockdown in Children and Adolescents With Overweight or Obesity.

BACKGROUND: The coronavirus disease pandemic is predicted to have adverse health effects on children and adolescents who are overweight or obese due to restricted school activity and stay-at-home orders. The purpose of this observational study was to determine the factors associated with weight gain in children and adolescents with overweight and obesity during coronavirus disease 2019 (COVID-19) lockdown. METHODS: Ninety-seven participants (sex- and age-specific body mass index (BMI) ≥ 85th percentile) were included. A baseline examination was conducted pre-COVID-19 (August 2019 to January 2020), and re-examination was performed post-lockdown (June to September 2020) and the results were compared. Correlation and regression analyses were conducted to investigate the association among changes in cardiometabolic markers and lifestyle behaviors with changes in BMI z-score. RESULTS: During the COVID-19 pandemic, an increase in BMI z-score (2.56 [2.01-2.94] to 2.62 [2.03-3.18]) was noticed in children and adolescents with obesity. Changes in cardiometabolic markers including liver enzymes, triglycerides (r = 0.398), leptin (r = 0.578), and adiponectin (r = -0.326), as well as muscular strength (r = -0.212), were correlated with the increase in BMI z-score. According to a multivariate regression analysis, changes in sedentary time (B = 0.016; 95% confidence interval [CI], 0.001-0.032) and fast-food consumption (B = 0.067; 95% CI, 0.013-0.122) were the lifestyle variables associated with BMI z-score increase. CONCLUSION: Changes in lifestyle behaviors including fast-food consumption and sedentary time during the COVID-19 pandemic may be associated with weight gain. In order to prevent health-related risks in children and adolescents with obesity during the pandemic, it is important to maintain the level of physical activity and healthy dietary habits.

Clinical and genetic features of four patients with Pearson syndrome: An observational study.

ABSTRACT: Pearson syndrome (PS) is a multisystem mitochondrial cytopathy arising from deletions in mitochondrial DNA. Pearson syndrome is a sporadic disease that affects the hematopoietic system, pancreas, eyes, liver, and heart and the prognosis is poor. Causes of morbidity include metabolic crisis, bone marrow dysfunction, sepsis, and liver failure in early infancy or childhood. Early diagnosis may minimize complications, but suspicion of the disease is difficult and only mitochondrial DNA gene testing can identify mutations. There is no specific treatment for PS, which remains supportive care according to symptoms; however, hematopoietic stem cell transplantation may be considered in cases of bone marrow failure.We herein describe the clinical and genetic characteristics of four patients with PS. One patient presented with hypoglycemia, two developed pancytopenia, and the final patient had hypoglycemia and acute hepatitis as the primary manifestation. All patients had lactic acidosis. Additionally, all patients showed a variety of clinical features including coagulation disorder, pancreatic, adrenal, and renal tubular insufficiencies. Two patients with pancytopenia died in their early childhood. Our experience expands the phenotypic spectrum associated with PS and its clinical understanding.

Additive Effects of Exercise or Nutrition Intervention in a 24-Month Multidisciplinary Treatment with a Booster Intervention for Children and Adolescents with Overweight or Obesity: The ICAAN Study.

This study compared the effects of a real-world multidisciplinary intervention with additional exercise or nutritional elements and investigated the effectiveness of a booster intervention after weight regain. A total of 242 children and adolescents (age- and sex-specific body mass index [BMI] ≥ 85th percentile, mean age: 10.82 years, 60% male) were allocated to three groups: usual care, exercise, or nutrition. Six-month active treatment with 1:1 session and a maintenance stage with group activities were repeated twice to comprise a 24-month intervention. The primary outcome was change % of the BMI z-score (zBMI). A total of 110 (45.4%) participants completed the 24-month intervention. A mixed-effects model analysis indicated no significant interaction effect of the intervention group and treatment phase on the zBMI change % (p = 0.976). However, there was a significant main effect of the treatment phase on zBMI change % at 6 months (ß = -2.98, [95% CI, -5.69-0.27]), 18 months (ß = -3.99, [95% CI, -6.76-1.22]), and 24 months (ß = -3.23, [95% CI, -5.94-0.52]; p = 0.042). The improvements in zBMI, body fat %, and cardiometabolic markers were observed only among males. Whereas the additive effect of intensive exercise or nutritional feedback was not detected in the long term, a booster intervention with 1:1 counseling was effective even after weight regain during the maintenance period. It may be useful to combine individualized counseling with a less intensive form of group care for long-term maintenance in a real-world setting.

Whole-body MRI evaluation in neurofibromatosis type 1 patients younger than 3 years old and the genetic contribution to disease progression.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common human genetic disease with age-dependent phenotype progression. The overview of clinical and radiological findings evaluated by whole-body magnetic resonance imaging (WBMRI) in NF1 patients < 3 years old assessed with a genetic contribution to disease progression is presented herein. METHODS: This study included 70 clinically or genetically diagnosed NF1 patients who received WBMRI before 3 years old. Clinical, genetic, and radiologic features were collected by retrospective chart review. In NF1+, widely spread diffuse cutaneous neurofibromas, developmental delay, autism, seizure, cardiac abnormalities, hearing defect, optic pathway glioma, severe plexiform neurofibromas (> 3 cm in diameter, disfigurement, accompanying pain, bony destruction, or located para-aortic area), brain tumors, nerve root tumors, malignant peripheral nerve sheath tumors, moyamoya disease, and bony dysplasia were included. RESULTS: The age at WBMRI was 1.6 ± 0.7 years old, and NF1 mutations were found in 66 patients (94.3%). Focal areas of signal intensity (FASI) were the most common WBMRI finding (66.1%), followed by optic pathway glioma (15.7%), spine dural ectasia (12.9%), and plexiform neurofibromas (10.0%). Plexiform neurofibromas and NF1+ were more prevalent in familial case (28.7% vs 5.7%, p = 0.030; 71.4% vs 30.2%, p = 0.011). Follow-up WBMRI was conducted in 42 patients (23 girls and 19 boys) after 1.21 ± 0.50 years. FASI and radiologic progression were more frequent in patients with mutations involving GTPase activating protein-related domain (77.8% vs 52.4%, p = 0.047; 46.2% vs 7.7%, p = 0.029). CONCLUSIONS: WBMRI provides important information for the clinical care for young pediatric NF1 patients. As NF1 progresses in even these young patients, and is related to family history and the affected NF1 domains, serial evaluation with WBMRI should be assessed based on the clinical and genetic features for the patients' best care.

Relationship Between Bone Mineral Density and Body Composition According to Obesity Status in Children.

OBJECTIVE: To analyze the relationship between body composition, metabolic parameters, and bone mineral density (BMD) according to sex and the degree of obesity in children and adolescents. METHODS: A total of 236 subjects with obesity, aged 10 to 15 years (36.9% girls), were enrolled. Obesity was classified into simple (SmOb) and extreme (ExOb) forms. The BMD of the total body, less head, was measured by dual energy x-ray absorptiometry, and the BMD z-score was used to evaluate the relationship of body composition with metabolic parameters. RESULTS: BMD z-scores were higher in subjects with ExOb than in those with SmOb. Lean mass index (LMI), body mass index z-score, and vitamin D intake showed positive relationships, whereas percentage of body fat and serum leptin level showed negative relationships with BMD z-scores in boys. In girls, LMI and body mass index z-score showed positive relationships with BMD z-scores. In multivariable linear regressions, serum leptin level showed negative relationships with BMD z-score, only in boys. In addition, positive relationships of LMI and negative relationships of percentage of body fat with BMD z-scores were observed in subjects with SmOb. However, positive relationships of LMI with BMD z-scores were attenuated in subjects with ExOb. CONCLUSION: High BMD appears to be positively associated with lean mass in children and adolescents with obesity, which might be a natural protective mechanism to withstand the excess weight. However, excessive body fat appears to be negatively associated with BMD, which might attenuate the positive relationship between lean mass and BMD in subjects with ExOb.

Association of Dietary Patterns with Weight Status and Metabolic Risk Factors among Children and Adolescents.

Unhealthy dietary patterns are associated with obesity in children and adolescents. However, few studies have investigated the relationships between dietary patterns and obesity-related metabolic disorders among Asians. We identified dietary patterns in children and adolescents and examined the associations between these patterns and obesity, insulin resistance, and metabolic syndrome in South Korea. This study is a cross-sectional design. We used baseline data from an intervention study of 435 Korean children and adolescents aged 6-17 years. Insulin resistance was assessed as HOMA-IR ≥ 2.6. Metabolic syndrome was diagnosed by cardiovascular disease risk factor clustering. Dietary intakes were estimated using 3-day food records. Factor analysis was used to obtain dietary patterns, and we examined the associations between dietary patterns and obesity-related markers adjusted for potential covariates. Three dietary patterns were identified as fast food and soda (FFS), white rice and kimchi (WRK), and oil and seasoned vegetable (OSV) patterns. Compared with participants in the lower intake of FFS pattern, those in the top intake were associated with a higher waist circumference (WC) (ß = 1.55), insulin level (ß = 1.25), and body mass index (BMI) (ß = 0.53) and it was positively associated with HOMA-IR ≥ 2.6 (OR = 2.11; 95% CI: 1.227-3.638) (p < 0.05). WRK pattern was associated with lower weight and higher HDL cholesterol, and the OSV pattern was associated with a lower weight, WC, and insulin level (p < 0.05). The FFS pattern showed a positive relation with WC, serum insulin, and BMI, and the other two dietary patterns indicated a preventive effect of those parameters. The FFS pattern was associated with significantly elevated insulin resistance among children and adolescents.

Effects of circuit training or a nutritional intervention on body mass index and other cardiometabolic outcomes in children and adolescents with overweight or obesity.

OBJECTIVE: We aimed to assess the effectiveness of the first 6 months of a 24 month multidisciplinary intervention program including circuit training and a balanced diet in children and adolescents with obesity. METHODS: A quasi-experimental intervention trial included 242 participants (age [mean±standard deviation]: 11.3±2.06 years, 97 girls) of at least 85th percentile of age- and sex-specific body mass index (BMI). Participants were grouped into three to receive usual care (usual care group), exercise intervention with circuit training (exercise group), or intensive nutritional and feedback intervention with a balanced diet (nutritional group). Primary outcome was BMI z-score, while secondary outcomes included body composition, cardiometabolic risk markers, nutrition, and physical fitness. RESULTS: Among the participants, 80.6% had a BMI ≥ the 97th percentile for age and sex. The BMI z-score of the overall completers decreased by about 0.080 after 6 months of intervention (p < 0.001). After the intervention, both exercise and nutritional groups had significantly lower BMI z-scores than the baseline data by about 0.14 and 0.075, respectively (p < 0.05). Significant group by time interaction effects were observed between exercise versus usual care group in BMI z-score (ß, -0.11; 95% confidence interval (CI), -0.20 to -0.023) and adiponectin (ß, 1.31; 95% CI, 1.08 to 1.58); and between nutritional versus usual care group in waist circumference (ß, -3.47; 95% CI, -6.06 to -0.89). No statistically significant differences were observed in any of the other secondary outcomes assessed. CONCLUSION: Multidisciplinary intervention including circuit training and a balanced diet for children and adolescents with obesity reduced the BMI z-score and improved cardiometabolic risk markers such as adiponectin and waist circumference.

A 24-week intervention based on nutrition care process improves diet quality, body mass index, and motivation in children and adolescents with obesity.

Higher motivation could support to lead behavioral change for obese children and adolescents. This study aimed to evaluate the effects of a nutrition care process (NCP)-based intervention targeted on diet and weight status in moderate to severe obese children and adolescents in Korea. One hundred four subjects (mean age: 10.95 years, body mass index (BMI) ≥97th percentile of age-sex) participated in the present study. Subjects were divided into a usual care group (UG) and a nutrition group (NG). All participants underwent nutrition education 6 times. The NG received individual access and continuous monitoring and setting goals with respect to nutritional problems. Consumption of high-calorie, low-nutrient (HCLN) food was significantly decreased (P < .05) and the Diet Quality Index-International (DQI-I) score also increased with respect to sodium (P < .001). The total self-efficacy score was increased from 9.15 to 10.14 points (P < .01). After 24 weeks, the BMI-z-score decreased from 2.27 to 2.19 in the NG (P < .05); however, no group difference was found. BMI-z-score was negatively associated with self-efficacy (ß = -0.03, P < .019). NCP-based intervention might be helpful to solve dietary problems by enhancing self-efficacy and lower BMI-z-score in moderately to severely obese children and adolescents.

Factors associated with dropout in a lifestyle modification program for weight management in children and adolescents.

BACKGROUND: Significant dropout rates remain a serious concern in pediatric weight control program, but few studies have identified predictors of dropout. AIMS: The objective of the study is to identify factors associated with dropout from a pediatric lifestyle modification weight control program at different phases. METHODS: Data on overweight and obese participants (n = 242) aged 11-18 years in the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition (ICAAN) study were collected at baseline, 6-months, and 24-months through self-report and a laboratory test. Logistic regression analysis was performed for those who dropped out during the first 6-months, and multivariate generalized estimating equation analysis identified longitudinal factors associated with those who dropped out after 24 months. RESULTS: Lower family functioning (OR = 2.30, 95% CI [1.18-4.46]), exercise group (OR = 0.36, 95% CI [0.15-0.86]), lower initial attendance rate (OR = 6.09, 95% CI [2.94-12.6]), and non-self -referral pathways (OR = 2.35, 95% CI [1.05-5.27]) were significantly associated with 6-month dropouts. For late dropout, lower family functioning (OR = 1.71, 95% CI [1.06-2.77]) and lower initial attendance rates (OR = 2.06, 95% CI [1.12-3.81]) remained significant. CONCLUSION: Family function and initial attendance rate were associated with lower dropout rates. Developing a supportive family environment and focusing on the early-stage factors at the intervention's outset may reduce overall dropout rates in obesity prevention intervention.

Evidence-based customized nutritional intervention improves body composition and nutritional factors for highly-adherent children and adolescents with moderate to severe obesity.

BACKGROUND/OBJECTIVES: Evidence-based customized nutritional interventions are required for effective treatment of moderate to severe obese children and adolescents. SUBJECTS/METHODS: Sixty six (64.1% of 103) of the eligible participants who joined the usual care or physical activity group in the clinic were involved in 16-week intervention. Customized nutritional intervention was implemented for each participant based on a nutrition care process (NCP) model. Sociodemographic assessment, anthropometrics data, health- and dietary-related behaviors, and dietary intake of the study subjects were assessed at baseline and follow-up. All participants engaged in 30-minute nutritional sessions on a monthly basis. RESULTS: After 16 weeks, there were significant improvements in body composition [BMI (-0.8 ± 0.9, P < 0.05), BMI z-score (-0.3 ± 0.2, P < 0.001), body fat (kg) (-1.3 ± 2.1, P < 0.05), and body fat (%)(-1.5 ± 1.9, P < 0.05)] as well as macronutrient intake [total energy intake (kcal) (-563.7 ± 656.8, P < 0.05), energy (%) (-26.5 ± 30.0, P < 0.05) and fat (g) (-28.3 ± 40.6, P < 0.05)] in the adherent group than the non-adherent group. The SOC was higher in both groups after the intervention (P < 0.001). CONCLUSIONS: Our results highlight the positive effects of an evidence-based approach as a multidisciplinary intervention for people-centered nutritional care and weight management.

Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types.

Neurofibromatosis type 1 (NF1) is caused by heterozygous mutation in the NF1 gene. NF1 is one of the most common human genetic diseases. However, the overall genotype-phenotype correlation has not been known, due to a wide spectrum of genotypic and phenotypic heterogeneity. Here we describe the detailed clinical and genetic features of 427 Korean NF1 patients from 389 unrelated families. Long range PCR and sequencing of genomic DNA with multiplex ligation-dependent probe amplification analysis identified 250 different NF1 mutations in 363 families (93%), including 94 novel mutations. With an emphasis on phenotypes requiring medical attention (classified and termed: NF1+), we investigated the correlation of NF1+ and mutation types. NF1+ was more prevalent in patients with truncating/splicing mutations and large deletions than in those with missense mutations (59.6%, 64.3% vs. 36.6%, p = 0.001). This difference was especially significant in the patients younger than age 19 years. The number of items in NF1+ was a higher in the former groups (0.95 ± 0.06, 1.18 ± 0.20 vs. 0.56 ± 0.10, p = 0.002). These results suggest that mutation types are associated not only with higher prevalence of severe phenotypes in NF1 but also with their earlier onset.

Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy.

BACKGROUND: Ambroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD. METHODS: ABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed. RESULTS: Enhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2-8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events. CONCLUSIONS: Long-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.

What Is the Role of Resistance Exercise in Improving the Cardiometabolic Health of Adolescents with Obesity?

Traditionally, individuals with obesity have been encouraged to participate in aerobic exercise for long-term weight management and improved obesity-related health outcomes. Recently, resistance exercise has become a popular mode of exercise among youth with obesity. However, to date, the literature is mixed as to whether resistance exercise training alone improves body weight, fat free mass, body composition, cardiovascular risk factors, or atherogenic lipoprotein profiles. The limited research in this area suggests potential sex differences in response to resistance training in youth. The literature is more consistent in demonstrating improvements in muscular fitness and insulin resistance independent of caloric restriction and weight loss. Although major health organizations recommend combining aerobic and resistance training, little research has examined the effects of their combination versus their individual effects, thus it is unclear whether their combination is associated with benefits that extend beyond those of either exercise modality alone. The purpose of this review is to examine the effects of resistance exercise on body composition and the health risk factors associated with cardiovascular disease and type 2 diabetes in youth with obesity.

The Effect of a Multidisciplinary Lifestyle Intervention on Obesity Status, Body Composition, Physical Fitness, and Cardiometabolic Risk Markers in Children and Adolescents with Obesity.

This study aimed to develop a multidisciplinary lifestyle intervention program targeted at children and adolescents with moderate to severe obesity, and assess the additional effects of exercise intervention when compared to usual care. Overall, the 103 enrolled participants were ≥85th percentile of age and sex-specific body mass index (BMI). Participants were divided into groups that received 16 weeks of either usual care or exercise intervention. The BMI z-score of the overall completers decreased by about 0.05 after the 16-week intervention (p = 0.02). After the intervention, only the exercise group had a significantly lower BMI z-score than the baseline score by about 0.1 (p = 0.03), but no significant group by time interaction effects were observed. At the 16-week follow-up, significant group by time interaction effects were observed in percentage body fat (%BF) (ß = -1.52, 95%CI = -2.58⁻-0.45), lean body mass (LM) (ß = 1.20, 95%CI = 0.12⁻2.29), diastolic blood pressure (ß = -5.24, 95%CI = -9.66⁻-0.83), high-sensitivity C-reactive protein (ß = -1.67, 95%CI = -2.77⁻-1.01), and wall sit test score (ß = 50.74, 95%CI = 32.30⁻69.18). We developed a moderate-intensity intervention program that can be sustained in the real-world setting and is practically applicable to both moderate and severe obesity. After interventions, the exercise group had lower %BF and cardiometabolic risk markers, and higher LM and leg muscle strength compared to the usual care group.