In recent years, there has been an increase in the prevalence of the diagnosis of attention-deficit/hyperactivity disorder (ADHD), a cognitive and behavioral disorder in which individuals present with inattention and impulsivity, in the pediatric population. With an increase in diagnoses, there is also increasing concern regarding overdiagnosis and overtreatment with medications for ADHD. The objective of this study was to map out and compile the recent literature pertaining to alternative therapies (e.g., physical activity, diet, mindfulness, and computer-based interventions) for children and adolescents diagnosed with ADHD in an attempt to reduce or replace the use of pharmacological therapy. This scoping review searched articles from multiple databases (PubMed, ScienceDirect, Web of Science, Directory of Open Access Journals, Scopus, and CINAHL). Using search terms \"children with ADHD,\" \"alternative treatment,\" and \"cognitive behavioral therapy,\" articles were identified that were specific to the research question. The inclusion criteria were patients under the age of 18 with a previous diagnosis of ADHD, no other comorbid illnesses, alternative treatments, and was limited to studies published between 2012 and 2022. After removing duplicates, screening for eligibility criteria, and conducting a critical appraisal of the articles, 16 articles were retained for the final review. The main alternative therapeutic domains that emerged were (1) physical activity, (2) diet, (3) mindfulness, (4) computer-based interventions, and (5) miscellaneous interventions. Seven articles assessed the effect of physical activity on executive and cognitive function in children and adolescents with ADHD. Most findings showed improvement with increased physical activity. Two articles explored the effect of diet on the improvement of ADHD symptoms and reported a positive impact. The two articles that evaluated the effects of mindfulness on ADHD symptoms reported a reduction in ADHD symptoms. Two studies evaluated the use of computer-based interventions as an adjunct treatment in children and adolescents with ADHD; improvements in symptoms were reported. One study each evaluated interventions based on music and nerve stimulation. These showed an improvement in attention, memory, and executive function. With the increasing prevalence of ADHD diagnosis in children and adolescents, alternative and/or adjunctive treatments may be a viable and valuable alternative to pharmaceutical interventions. The findings from this review suggest that multiple non-pharmacological interventions effectively reduce symptoms of ADHD in children and adolescents, including diet, exercise, mindfulness, computer-based interventions, music, and nerve stimulation. While there are implications for alternatives to be used in the future, more research is warranted using larger samples with controlled trials.

The long-term use of pediatric medications can lead to discoloration of dental restorations, which affects their durability and longevity. The present in vitro study evaluated the effects of commonly used pediatric medications on the color stability of a conventional and a bulk-fill composite resin. For this study, 80 disc-shaped specimens of each composite were prepared in molds with a diameter of 6 mm and thicknesses of 2 or 4 mm (n = 40 per thickness per material). A spectrophotometer was used to evaluate the baseline color of the specimens in the International Commission on Illumination L*a*b* color space. Each specimen was immersed separately in a container holding 1 of 8 liquid medications (n = 5 per thickness per medication): amoxicillin/clavulanate, clarithromycin, cephalexin, acetaminophen, ibuprofen, levetiracetam, multivitamin, or albuterol. After the container was shaken for 2 minutes, the specimen was removed from the medication and stored in artificial saliva. The cycle was repeated every 8 hours for 1 week. The color measurements were repeated after 1 week of immersion cycles, and the overall color change (ΔE*) was calculated; a value of ΔE* > 3.3 was considered clinically perceptible. The data were analyzed with 1-way and 2-way analyses of variance as well as the Levene test and Games-Howell post hoc test (P < 0.05). All specimens displayed clinically perceptible color changes after exposure to medications commonly used by children. The mean color change in the 4-mm bulk-fill composite resin group was significantly greater than that in all other groups (P < 0.05). However, there was no significant difference in color change based on the immersion drug for either of the composites (P > 0.05). The study findings show that exposure of composite resin to certain commonly used pediatric drugs causes color changes that are clinically perceptible.

OBJECTIVE:  To investigate the color stability of light-cured (LC) restorative material in different pediatric drug formulations.
METHODS:  Two distinct restorative materials, specifically LC resin and LC glass ionomer cement (GIC), were employed to create 88 disc-shaped specimens. These comprised 44 specimens fabricated from each material. Each specimen had a diameter of 5 mm and a height of 3 mm. To conduct the experiment, specimens were randomly allocated into four experimental groups, each containing 11 specimens made of each material. This division was accomplished through the use of a stratified random sampling method. The five experimental groups and their respective liquid medications were as follows: Group 1 - montelukast sodium and levocetirizine dihydrochloride syrup, Group 2 - cefixime, Group 3 - sodium valproate, and Group 4 - metronidazole. To ensure thorough exposure to the medications, all samples underwent a two-minute agitation cycle, which was repeated every 12 h over the course of one week. Following the immersion period, the color stability of all specimens was assessed using a spectrophotometer. The data obtained from the color stability measurements were subjected to statistical analysis using one-way analysis of variance (ANOVA), followed by a post hoc test. The aim was to determine whether significant differences in color stability were observed among the groups studied.
RESULTS:  The mean values and standard deviations of ΔE were calculated. The highest values of ΔE were observed in Group 3 (4.70 ± 1.89), followed by Group 4 (4.04 ± 2.10). Conversely, the lowest ΔE values were observed in Group 2 (3.23 ± 2.02) and Group 1 (3.24 ± 2.31). The calculated p-value was 0.298, and the F-value was 1.269.
CONCLUSIONS:  This study concludes that both restorative materials, LC composite and LC GIC, are susceptible to discoloration. Sodium valproate exhibited the greatest staining effect on both materials. Conversely, cefixime had the least impact on the color of the LC composite, whereas montelukast had the least effect on the color of LC GIC.

The development of oral pediatric forms by pharmaceutical companies is still insufficient. In fact, many drugs used in paediatric oncology, such as temozolomide, are not labeled and adapted for paediatric use. Temozolomide (TMZ) is an alkylating agent used as the standard of care for many adult and pediatric brain tumours, such as neuroblastoma, glioblastoma and medulloblastoma. The present study was carried out to propose a suitable and palatable formulation of the oral liquid preparation of TMZ. The suspension is composed of TMZ suspended in SyrSpend SF pH 4, as well as TMZ crystallization stabilizing agents and sweetening agents. To reach this formulation, several taste-masking agents were evaluated. Here, we describe the method of preparation of the formation as well as the monocentric population treated with the formulation over a 5-year period. A 20 mg/mL TMZ suspension was developed. TMZ suspension is stable for 6 weeks, stored between 2 and 8 degrees, protected from light, and compatible with nasogastric tubes. Thirty-eight patients participated in the palatability study and choose cola flavour, and 104 patients were treated in Gustave Roussy with the developed suspension; no unexpected event was reported. To conclude, we propose here a new TMZ liquid formulation which is stable for at least 6 weeks and well-tolerated with extensive feedback.

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OBJECTIVE: The recommended first-line treatment for young children infected with HIV includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra® [Abbott Laboratories, Chicago, Illinois]). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas others strongly reject it, which can deter therapeutic adherence and outcomes.
METHODS: As a proof-of-concept approach, a sensory panel of genotyped adults was used to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients. Panelists rated taste sensations using generalized labeled magnitude scales to determine genotype-phenotype relationships. Several months later, the panelists were retested to assess response reliability.
RESULTS: Not all panelists had the same sensory experience when tasting Kaletra. Palatability ratings varied widely, from moderate like to strongest imaginable dislike, and were reliable over time. The more irritating and bitter Kaletra tasted, the more disliked by the panelist. The more they disliked the taste of Kaletra, the more they disliked the taste of its excipient ethanol and the bitter stimulus denatonium. Those who experienced less bitter and sweeter taste sensations had a different genetic signature than the other panelists. Bitterness and irritation ratings of Kaletra varied by the orphaned bitter receptor gene (TAS2R60), whereas sweetness ratings of Kaletra varied according to the cold receptor gene (TRPM8), which is activated by menthol, an excipient of Kaletra. Neither genotype related to ratings for ethanol or denatonium, however.
CONCLUSIONS: The use of a sensory panel holds promise as a first step in determining the nature of individual differences in the palatability of existing pediatric drug formulations and sources of variation. In this era of personalized medicine, the need is great to develop psychophysical tools to determine which drugs will show variation in acceptance by children and whether patterns of individual variation in taste as assessed by adults mirror those of young patients. ClinicalTrials.gov identifier: NCT01841710.

There is a need for information on the bioavailability in pediatric patients of drugs from manipulated dosage forms when applied in combination with food and/or co-medication under realistic daily practice circumstances. We describe the development, validation and application of a dynamic, computer-controlled in vitro system mimicking the conditions in the upper gastrointestinal tract of neonates, infants and toddlers: TIMpediatric. Paracetamol and diclofenac in age-related food matrices and with esomeprazole co-medication were tested. The experiments showed relevant results on the impact of drug manipulation and co-medication on the availability for absorption of active compounds. Without ethical constraints, alternative approaches for oral dosing and new pediatric formulations can be studied in TIMpediatric with a high predictive value.