New kids on the CPET: age-appropriate outdoor cardiopulmonary exercise testing in preschoolers

Purpose Cardiopulmonary exercise testing (CPET) in preschoolers (4–6 years) represents a challenge. Most studies investigating CPET have been limited to older children (> 8 year). However, knowledge of the performance of small children is essential for evaluating their cardiorespiratory fitness. This study strives to compare a modified Bruce protocol with a new age-appropriate incremental CPET during natural movement running outdoors, using a mobile device. Methods A group of 22 4–6-year-old healthy children was tested indoor on a treadmill (TM) using the modified Bruce protocol. The results were compared with a self-paced incremental running test, using a mobile CPET device in an outdoor park. The speeds were described as (1) slow walking, (2) slow running, (3) regular running, and (4) running with full speed as long as possible. Results Mean exercise time outdoors (6,57 min) was significantly shorter than on the treadmill (11,20 min), $$\dot{V}{O}_{2peak}$$ V ˙ O 2 p e a k (51.1 ml/min/kg vs. 40.1 ml/min/kg), RER (1.1 vs. 0.98) and important CPET parameters such as $$\dot{V}E$$ V ˙ E max, O2pulse, heart rate and breath rate were significantly higher outdoors. The submaximal parameter OUES was comparable between both the tests. Conclusions Testing very young children with a mobile device is a new alternative to treadmill testing. With a significantly shorter test duration, significantly higher values for almost all cardiopulmonary variables can be achieved without losing the ability to determine VT1 and VT2. It avoids common treadmill problems and allows for individualized exercise testing. The aim is to standardize exercise times with individual protocols instead of standardizing protocols with individual exercise times, allowing for better comparability.

Functional outcomes in children related to self-care, mobility, and social function after stroke in early childhood: a cohort study

ABSTRACT Background: Stroke has been increasingly recognized as an important morbidity and mortality factor in neonates and children. Children have different and more diverse risk factors than adults, commonly related to an underlying disease. Stroke may compromise functional capacity in children. Few studies have focused on functional outcomes related to activities and participation. Objectives: To investigate post-stroke functionality of children related to self-care, mobility, and social function. Methods: We assessed the functional outcome of 14 children younger than 7.5 years who suffered a stroke in early childhood through the use of the Pediatric Evaluation of Disability Inventory (PEDI). Results: The average age of the sample at assessment was 3.6 ± 1.4 years (2 - 6 years). The average scores in the PEDI functional domains of self-care, mobility, and social function were, respectively, 37.6 ± 15.4, 36.2 ± 15.4, and 48.7 ± 11.1. Children showed age-appropriate functional outcomes in the PEDI functional domains: 71.4% of them in self-care and mobility and 92.9% in social function. Children with bilateral injuries (p = 0.05) and longer hospital stays (r = -0.79, p = 0.001) showed the worst scores in PEDI's social function domains. Conclusions: Overall, our sample of preschool children showed age-appropriate functional outcomes on self-care, mobility, and social function domains after stroke. However, children with bilateral injuries and longer hospital stays showed the worst scores in social function domains. We recommend focusing on functional rehabilitation to promote activities and participation and to monitor the development of children's social skills after stroke.

Performance Evaluation of Montelukast Pediatric Formulations: Part II — a PBPK Modelling Approach

This study aimed to build a physiologically based pharmacokinetic (PBPK) model coupled with age-appropriate in vitro dissolution data to describe drug performance in adults and pediatric patients. Montelukast sodium was chosen as a model drug. Two case studies were investigated: case study 1 focused on the description of formulation performance from adults to children; case study 2 focused on the description of the impact of medicine co-administration with vehicles on drug exposure in infants. The PBPK model for adults and pediatric patients was developed in Simcyp® v18.2 informed by age-appropriate in vitro dissolution results obtained in a previous study. Oral administration of montelukast was simulated with the ADAM™ model. For case study 1, the developed PBPK model accurately described montelukast exposure in adults and children populations after the administration of montelukast chewable tablets. Two-stage dissolution testing in simulated fasted gastric to intestinal conditions resulted in the best description of in vivo drug performance in adults and children. For case study 2, a good description of in vivo drug performance in infants after medicine co-administration with vehicles was achieved by incorporating in vitro drug dissolution (under simulated fasted gastric to fed intestinal conditions) into a fed state PBPK model with consideration of the in vivo dosing conditions (mixing of formulation with applesauce or formula). The case studies presented demonstrate how a PBPK absorption modelling strategy can facilitate the description of drug performance in the pediatric population to support decision-making and biopharmaceutics understanding during pediatric drug development. Graphical abstract

Performance Evaluation of Montelukast Pediatric Formulations: Part I—Age-Related In Vitro Conditions

This study aimed to explore the potential of biopharmaceutics in vitro tools to predict drug product performance in the pediatric population. Biorelevant dissolution set-ups were used to predict how age and medicine administration practices affect the in vitro dissolution of oral formulations of a poorly water-soluble compound, montelukast. Biorelevant age-appropriate dissolution studies of Singulair® (granules and chewable tablets) were conducted with the µDISS profiler™, USP 4 apparatus, USP 2 apparatus, and mini-paddle apparatus. Biorelevant simulating fluids representative of adult and pediatric conditions were used in the dissolution studies. The biorelevant dissolution conditions were appropriately selected (i.e. volumes, transit times, etc.) to mimic the gastrointestinal conditions of each of the subpopulations tested. Partial least squares regression (PLS-R) was performed to understand the impact of in vitro variables on the dissolution of montelukast. Montelukast dissolution was significantly affected by the in vitro hydrodynamics used to perform the dissolution tests (µDISS profiler™: positive effect); choice of simulation of gastric (negative effect) and/or intestinal conditions (positive effect) of the gastrointestinal tract; and simulation of prandial state (fasted state: negative effect, fed state: positive effect). Age-related biorelevant dissolution of Singulair® granules predicted the in vivo effect of the co-administration of the formulation with applesauce and formula in infants. This study demonstrates that age-appropriate biorelevant dissolution testing can be a valuable tool for the assessment of drug performance in the pediatric population. Graphical Abstract

Patient Centricity Driving Formulation Innovation: Improvements in Patient Care Facilitated by Novel Therapeutics and Drug Delivery Technologies

Innovative formulation technologies can play a crucial role in transforming a novel molecule to a medicine that significantly enhances patients’ lives. Improved mechanistic understanding of diseases has inspired researchers to expand the druggable space using new therapeutic modalities such as interfering RNA, protein degraders, and novel formats of monoclonal antibodies. Sophisticated formulation strategies are needed to deliver the drugs to their sites of action and to achieve patient centricity, exemplified by messenger RNA vaccines and oral peptides. Moreover, access to medical information via digital platforms has resulted in better-informed patient groups that are requesting consideration of their needs during drug development. This request is consistent with health authority efforts to upgrade their regulations to advance age-appropriate product development for patients. This review describes formulation innovations contributingto improvements in patient care: convenience of administration, preferred route of administration, reducing dosing burden, and achieving targeted delivery of new modalities.

Mindfulness and the Elderly

With growing life expectancy, age-related mental health issues are rising in the elderly. Whether normal aging or pathological senility, mindfulness practices are useful, economic, and accessible. The elderly experience many forms of anxiety with varying severity. There can be stress, anxiety, depression, and negative emotions. Quality of life and sleep, cognitive impairments, chronic pain, decreased social contacts are common concerns of the elderly. There is growing evidence that mindfulness practices mitigate their suffering. This chapter covers details on mindfulness-based tools for the elderly, their practices, exercises, and techniques. The recommended techniques are group-based, participatory, age-appropriate, and reflective. Given the vulnerability of the elderly, the chapter cautions about latent medico-legal and ethical issues in using mindfulness for the elderly. They must be blended with cultural, religious, moral, and spiritual elements to derive optimum benefits for the individual or small groups of such persons. A future road map is given.

Design of Signed Language Tests for Deaf L1 Children

Recent changes in the earlier diagnosis of deafness and improved amplification options have meant that deaf children increasingly have better opportunities to develop spoken language. Nevertheless, a significant proportion of children continue to use signed language as a first language (L1), including deaf and hearing children in deaf signing families and deaf children in hearing families where families use signed language in the home. For both groups, mastery of sign language as an L1 is important because it paves the way to communication and also because it provides the basis for development of spoken language, in either its oral or written form, as a second language (L2). It is crucial that signed language development proceeds in an age-appropriate manner, and assessments of signed language are therefore important to ensure that this is the case. However, the development of effective tests of signed language acquisition is not without challenges. This chapter presents these challenges and other issues and gives examples of how available tests seek to overcome them.

Application of Healthy and Safe Internet in Controlling Negative Internet Impacts for Students at MI Darussa'adah, South Jakarta.

The use of gadgets today has become a major requirement for everyone. In the present, many children are using gadget since childhood especially to watch videos on youtube, play online games, and search for learning materials through the help of the internet.This can be a good step so that children easily adapt to technological developments. But on the other hand, parents must worry if children play gadgets too often and access things that are not age-appropriate, which is not necessarily suitable for their age. It is important for parents to monitor the use of gadgets in children. The role of parents and teachers in dealing with this situation, they must have the ability to monitor and control the use of the internet by parental control applications. It is able to select, limit, and supervise what applications can be accessed by children and adolescents so they can still use gadgets as a learning and entertainment medium without having to be addicted and poisoned by negative content.