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There are no validated measures to assess hyperphagia associated with rare MC4R pathway diseases, such as Bardet-Biedl Syndrome (BBS). Symptoms of Hyperphagia© (SoH) and Impacts of Hyperphagia© (IoH) are novel questionnaires designed to assess signs and symptoms of hyperphagia and their impacts on patients and caregivers. We evaluated the psychometric performance of the caregiver-versions of the SoH: Caregiver (Observer-reported) and IoH: Caregiver (Observer-reported and Self-reported subscales). Reliability and validity were evaluated using data from a multi-country cross-sectional survey of adult caregivers of patients with BBS experiencing hyperphagia and obesity. Other instruments included were Impact of Weight on Quality of Life (IWQOL)-Kids (Parent Proxy), PROMIS Scale Global Health of Caregiver, Revised Impact on Family Scale (RIOFS), and Work Productivity and Activity Impairment. 242 eligible caregivers completed the survey. Exploratory factor analysis identified 1 factor per subscale. Strong internal consistency was observed for IoH: Caregiver (Observer) (Cronbach's a = 0.66) and IoH: Caregiver (Self) (a = 0.72) and moderate for SoH: Caregiver (Observer) (a = 0.40). Moderate-to-strong correlations were observed with school days missed and all domains of IWQOL-Kids except Physical Comfort (range = 0.315-0.573, p's < 0.001). Known-groups indicated significantly worse SoH: Caregiver subscores for patients using appetite suppressants or implementing more weight management approaches (6-10 vs. ≤5 or > 10). Caregivers reporting greater strain on RIOFS items and worse mental health had worse IoH subscores. The SoH: Caregiver and IoH: Caregiver demonstrated preliminary validity, reliability, and consistency in a real-world setting. Research is underway to further validate these measures for use in clinical trials for BBS and other MC4R pathway-related diseases associated with obesity.

This study measured the effectiveness and feasibility of therapeutic drumming for autistic children, targeting the meaningful occupational components of authentic social and personal participation of children. A 6-week therapeutic drumming intervention was implemented interprofessionally in two early-childhood classrooms with ten autistic children (N = 10), ages two through six. Two outcome measures were completed pre- and post-intervention: the Behavior Assessment System for Children, Third Edition (BASC-3), the Social and Personal Relationship Scale (SPRS). Descriptive statistics on pre- and post-intervention mean scores were generated and Wilcoxon signed rank tests were used to determine the areas where mean score changes were statistically significant. Significant differences were found between each component of the SPRS, and on two BASC-3 subsections (e.g. response to teacher, transition movement). Misalignment between language on the BASC-3 and neurodiversity affirming practice was identified as a notable limitation of the study. Feedback collected from lead facilitators regarding efficacy and implementation feasibility was collected via interview following the program. The implication of this pilot study provides preliminary evidence supporting the effectiveness and feasibility of therapeutic drumming, which must be further explored.

BackgroundRapid and abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment-related damage to the hypothalamus, is called acquired hypothalamic obesity (aHO), and is often linked to craniopharyngioma and/or sellar/suprasellar tumors. Here, we examine the healthcare resource use (HCRU) and costs of aHO following treatment of these tumors.MethodsWe used a retrospective matched cohort design with German statutory health insurance data on 5.42 million people from 2010 to 2021. We applied a novel three-step approach using diagnostic and prescription data to identify patients with treatment- or tumor-related (TTR)-aHO. We measured HCRU and costs across hospitalizations, outpatient visits, visits per specialist group, and outpatient prescription medications.ResultsCompared to non-HO obesity, TTR-aHO is associated with increased hospitalizations, increased outpatient physician visits, and increased prescription use in the two years after incident tumor surgery/radiotherapy. Excess costs of TTR-aHO are €19,900 per patient in the first year and €10,700 in the second, driven by inpatient costs. Cost-intensive hormone replacement therapies like somatropin lead to a sharp increase in prescription costs in the second year.ConclusionsThis study provides the first real-world analysis of TTR-aHO economics, emphasizing the importance of HCRU and costs for decision-making. Previously, economic evaluations have been missing due to the lack of a standard method to identify patients with aHO in retrospective studies. Using a new identification approach, the study reveals that TTR-aHO poses a significant burden in extensive treatment requirements for patients and high related costs for the healthcare system.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10198-025-01786-3.

Abstract BackgroundDuring atypical atrioventricular nodal reentrant tachycardia (AVNRT), the earliest atrial activation site following retrograde slow pathway (SP) conduction is at the atrial exit of the left inferior extension of the compact node (LIE) in the coronary sinus (CS) or the right inferior extension (RIE) on the tricuspid annulus (TA). We tested the validity of conventional electrode placement-based mapping of the atrial ends of these extensions.MethodsWe retrospectively evaluated the efficiency of the two catheter (His bundle and CS) mapping method for localization of LIE and RIE in atypical AVNRT patient using electroanatomical 3D mapping validation.ResultsAmong 19 atypical AVNRTs (15 fast/slow and 4 slow/slow) in 14 patients (9 females, age 59±17), 8 AVNRTs had LIE involvement and 11 had RIE. The 8 LIE exits were inside the CS, and localization by 3D mapping and CS electrode catheter matched in all. In contrast, RIE exits were on the posterior TA where electrode catheters are conventionally not placed. All RIE exits required 3D mapping for accurate localization. During retrograde RIE conduction, comparison of the activation time of the CS ostium and HBE showed that the CS ostium was earlier in 7 RIEs, HBE was earlier in 1, and they were simultaneous in 3, resulting in the presence of RIE being missed in 4/11 (36%) AVNRTs using current diagnostic criteria. Activation time of the CS ostium and His bundle were determined by their relative closeness to the RIE exit.ConclusionsConventionally placed electrode catheter mapping in atypical AVNRT was able to identify 100% of LIE, but only 64% of RIE. It is critical to place a catheter on or use a 3D mapping system for the posterior TA in cases of suspected atypical AVNRT, so that all inferior extensions of the AV node can be identified and targeted for treatment.

In the mass production of multi-element silicon p-i-n photodiodes, the problem of systematic rejection of products due to a decrease in the insulation resistance between the active elements of photodetectors has been revealed. The purpose of this work is to study the causes of insulation resistance degradation and to establish optimal methods for avoiding this phenomenon. A comparative analysis of three insulation methods was carried out: classical insulation by the surface of a non-conductive substrate and a dielectric layer; insulation by means of mesaprofile grooves with a dielectric film; insulation by means of areas of limitation of surface leakage channels isotypic with the substrate material (in this case, p+-type) formed in the gaps between active elements. The study found that the reason for the deterioration of the insulation resistance between the active elements of photodiodes is the presence of conductive inversion channels at the Si-SiO2 interface due to the use of silicon with high resistivity. One mechanism for the formation of inversion channels is the redistribution of impurities in the masking oxide (in particular, phosphorus) and their diffusion to the interface during thermal operations. Another mechanism for the formation of inversion layers is the diffusion of boron from silicon into SiO2 during heat treatment due to the fact that the boron segregation coefficient is less than one. In the manufacture of samples with insulation using non-conductive areas of the substrate, a decrease in insulation resistance was observed as the technological route was performed (after each subsequent operation, the resistance degraded). The degree of degradation can be reduced by reducing the duration of thermal operations. It has been shown that reducing the thickness of the masking oxide causes a decrease in insulation resistance. When using mesa-technology, it is possible to increase the insulation resistance by eliminating the high-temperature oxidation operation and, in fact, due to the absence of a masking coating during phosphorus deposition. Insulation by means of p+-type areas in the gaps between the active elements allows to obtain the highest insulation resistance values. The formation of these regions with a width of 100 μm in the gaps with a width of 200 μm allowed us to obtain an insulation resistance of 25-30 MΩ. To ensure the insulation of the active elements of photodiodes by this method, two thermal operations are added to the technological route. The number of thermal operations can be reduced by doping the entire silicon surface with a low boron concentration before forming a masking coating.

BackgroundSigns and symptoms of Bardet–Biedl syndrome (BBS) occur during early childhood, progress over time, and place substantial, multifaceted burden on patients and their caregivers. Hyperphagia may be a contributing factor to early-onset obesity in BBS; however, there are limited insights into its impacts on patients and caregivers. We quantified disease burden as it relates to the physical and emotional impacts of hyperphagia in BBS.MethodsThe CAREgiver Burden in BBS (CARE-BBS) study was a multicountry, cross-sectional survey of adult caregivers of patients with BBS who have had hyperphagia and obesity. The survey consisted of questionnaires including Symptoms of Hyperphagia, Impacts of Hyperphagia, Impact of Weight on Quality of Life (IWQOL)-Kids Parent Proxy, and Patient-Reported Outcome Measurement Information System (PROMIS) v1.0-Global Health 7. In addition, clinical characteristics, medical history, and weight management questions were included. Outcomes were scored and summarized descriptively in aggregate and by country, age, and obesity severity according to weight class.ResultsThere were 242 caregivers of patients with BBS who completed the survey. Caregivers observed hyperphagic behaviors throughout the day, with negotiating for food (90%) and waking up and asking or looking for food during the night (88%) being the most frequent. Hyperphagia had at least a moderate negative impact on most patients’ mood/emotions (56%), sleep (54%), school (57%), leisure (62%), and familial relationships (51%). Hyperphagia affected concentration at school (78%), and symptoms of BBS contributed to patients missing ≥ 1 day of school a week (82%). Responses from the IWQOL-Kids Parent Proxy suggested obesity most greatly negatively affected physical comfort (mean [standard deviation (SD)], 41.7 [17.2]), body esteem (41.0 [17.8]), and social life (41.7 [18.0]). On the PROMIS questionnaire, mean (SD) global health score for pediatric patients with BBS and overweight or obesity (36.8 [10.6]) was lower than the general population (mean, 50).ConclusionsEvidence from this study suggests that hyperphagia and obesity may have broad negative impacts on the lives of patients with BBS, including physical health, emotional well-being, school performance, and personal relationships. Therapies that target hyperphagia may alleviate the extensive clinical and nonclinical impacts experienced by patients with BBS and their caregivers.

IntroductionBardet-Biedl syndrome (BBS) is a rare genetic disease associated with hyperphagia, a pathologic insatiable hunger, due to impaired signaling in the melanocortin-4 receptor (MC4R) pathway. The impact of hyperphagia on the lives of patients with BBS and their families has not been fully characterized.MethodsPatients with BBS or their caregivers who participated in clinical trials of the MC4R agonist setmelanotide (NCT03013543 and NCT03746522) were included in this qualitative study. Telephone interviews were conducted using a semistructured interview guide to explore patient experience and caregiver observations of hyperphagia before and during setmelanotide treatment.ResultsNineteen interviews (8 patients, 11 caregivers) were conducted. The term “hunger” (rather than “hyperphagia”) was used in interviews to ensure common terminology. Before setmelanotide treatment, all participants described their (or their child’s) hunger as all-consuming, leading to an obsessive focus on food. Nine participants recalled intense, continuous hunger, and most participants (5 patients, 10 caregivers) reported lack of control with eating. Negative impacts on patients’ lives included difficulties with concentration, emotional and physical manifestations, and impaired relationships. All participants experienced or observed improvements in hunger and health outcomes during treatment, the most meaningful of which included weight loss and decrease in obsessive focus on food and food-seeking behaviors. All participants reported improvements in either physical and/or emotional well-being and being satisfied with setmelanotide.ConclusionsHyperphagia and resulting food-seeking behaviors have notable negative impacts on quality of life in patients with BBS and caregivers. Setmelanotide improved hyperphagia, reduced body weight and obsessive focus on food, and facilitated improvements in physical and emotional well-being for both patients and caregivers.Trial RegistrationNCT03013543 and NCT03746522Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-023-02443-y.