Effects of a Virtual Reality Game on Children's Anxiety During Dental Procedures (VR-TOOTH): Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Dental fear and anxiety (DFA) is a condition that affects approximately one-quarter of children and adolescents. It is a significant cause for pediatric patients to avoid dental care later in adulthood. Lack of patient cooperation due to DFA can create an environment of stress, often obligating dentists to end appointments prematurely and consider alternative pharmacological treatment options. Virtual reality (VR) use during dental care, providing an immersive experience through sensory stimuli, is potentially an additional nonpharmacologic tool to better manage DFA in children with special health care needs (SHCN) undergoing dental procedures. OBJECTIVE: This pilot study aims to assess the feasibility and acceptability of VR immersion as a tool to reduce DFA in pediatric special needs patients undergoing dental procedures. The study also aims to gain insight on parent and health care provider perspectives on the use of VR during dental appointments. METHODS: This pilot randomized controlled trial study will follow a parallel design including 2 groups: a control group (clinic's standard care using a wall TV) and an experimental group (using a VR game). We will randomize 20 participants to either group. Recruitment will be carried out at the dental clinic of the Centre Hospitalier Universitaire Sainte-Justine, a tertiary-quaternary care center that mostly serves pediatric patients with SHCN. The primary outcome will be patient recruitment rates and completion rates of planned procedures. DFA in children will be assessed using both an observation-based proxy assessment with the Venham Anxiety and Behavior Rating Scale and physiological assessments using parameters such as change in heart rate and levels of salivary alpha-amylase as a stress biomarker before and 10 minutes after the procedure. Sociodemographic characteristics, measures of the levels of parent and health care professional satisfaction, occurrence of side effects, and any deviation from normal procedure length will also be collected. Descriptive statistics, nonparametric tests, and effect sizes will be used for demographic and clinical variables and to present parent and health care professional satisfaction levels as well as procedural time. RESULTS: This study will be conducted from May 2023 to May 2024, with results expected to be available in December 2024. CONCLUSIONS: The pilot study will provide insight on the feasibility and acceptability of VR use in clinical dentistry to reduce DFA for pediatric patients with SHCN. This study will guide future research on VR use in pediatric dentistry and can serve as a framework for a larger randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05898100; https://classic.clinicaltrials.gov/ct2/show/NCT05898100. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49956.

The Three W's of Acetaminophen In Children: Who, Why, and Which Administration Mode.

Acetaminophen is one of the oldest medications commonly administered in children. Its efficacy in treating fever and pain is well accepted among clinicians. However, the available evidence supporting the use of acetaminophen's different modes of administration remains relatively scarce and poorly known. This short report summarizes the available evidence and provides a framework to guide clinicians regarding a rational use of acetaminophen in children.

The Efficacy of Virtual Reality Game Preparation for Children Scheduled for Magnetic Resonance Imaging Procedures (IMAGINE): Protocol for a Randomized Controlled Trial.

BACKGROUND: It is known that magnetic resonance imaging (MRI) procedures generate fear and anxiety. Children may become restless during scanning, which results in movement artifacts requiring the MRI procedure to be repeated with sedation. Few studies seem to have looked at the effect of immersive virtual reality (IVR) on anxiety in children scheduled for MRI scans and how to identify which children are more responsive. OBJECTIVE: The aims of this study are 3-fold: develop an algorithm of predictability based on biofeedback, address feasibility and acceptability of preprocedural IVR game preparation for anxiety management during MRI procedures, and examine the efficacy of IVR game preparation compared with usual care for the management of procedural anxiety during MRI scans. METHODS: This study will have 2 phases. We will first conduct a field test with 10 participants aged 7 to 17 years to develop a predictive algorithm for biofeedback solution and to address the feasibility and acceptability of the research. After the field test, a randomized controlled trial will be completed using a parallel design with 2 groups: an experimental group (preprocedural IVR game preparation) and a usual care group (standard care as per the radiology department's protocol) in an equal ratio of 49 participants per group for 98 participants. Recruitment will be carried out at a hospital in Quebec, Canada. The experimental group will receive a preprocedural IVR game preparation (IMAGINE) that offers an immersive simulation of the MRI scan. Participants will complete a questionnaire to assess the acceptability, feasibility, and incidence of side effects related to the intervention and the biofeedback device. Data collected will include sociodemographic and clinical characteristics as well as measures of procedure-related anxiety with the French-Canadian version of the State-Trait Anxiety Inventory for Children (score 1-3) and the Children's Fear Scale (score 0-4). Physiological signs will be noted and include heart rate, skin conductance, hand temperature, and muscle tension. Measures of the level of satisfaction of health care professionals, parents, and participants will also be collected. Analyses will be carried out according to the intention-to-treat principle, with a Cronbach α significance level of .05. RESULTS: As of May 10, 2022, no participant was enrolled in the clinical trial. The data collection time frame is projected to be between April 1, 2022, and March 31, 2023. Findings will be disseminated through peer-reviewed publications. CONCLUSIONS: Our study provides an alternative method for anxiety management to better prepare patients for an awake MRI procedure. The biofeedback will help predict which children are more responsive to this type of intervention. This study will guide future medical practice by providing evidence-based knowledge on a nonpharmacological therapeutic modality for anxiety management in children scheduled for an MRI scan. TRIAL REGISTRATION: ClinicalTrials.gov NCT04988516; https://clinicaltrials.gov/ct2/show/NCT04988516. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30616.

Virtual reality mobility for burn patients (VR-MOBILE): A within-subject-controlled trial protocol.

In the acute phase, burn patients undergo several painful procedures. Pediatric burn care procedures conducted in hydrotherapy have been known to generate severe pain intensity and moderate to high levels of anxiety. Hydrotherapy treatments are done with the use of opioids and benzodiazepines for pain and anxiety. Unfortunately, nonpharmacological methods are rarely combined with pharmacological treatments despite evidence showing that distraction can serve as an effective method for pain management and can potentially decrease analgesic requirements in other painful medical procedures. Virtual reality (VR) is a method that uses distraction to interact within a virtual environment. The use of VR is promising for pain reduction in varying settings. Considering the lack of optimal pain and anxiety management during burn wound care and the positive effect of an immersive distraction for painful procedures, using VR for burn wound care procedures may show promising results. This is a within-subject randomized controlled trial design in which each participant will serve as his/her own control. A minimum of 20 participants, aged 7 to 17 years old undergoing a burn care session, will receive both standard and experimental treatments during the same session in a randomized order. The experimental treatment will consist of combining VR distraction using the video game Dreamland® to the current standard pharmacological care as per unit protocol. The control group will only receive the unit's standard pharmacological care. The mean difference in both pain intensity scores and in anxiety between the two different sequences will be the primary outcomes of this study. This study evaluates the effect of VR on burn wound care. If results from this study show a positive effect of VR compared to standard care, this protocol may provide guidance on how to implement this type of immersive care as part of the tools available for distraction of painful procedures for acute burn victims.

Reopening Schools After a Novel Coronavirus Surge.

The coronavirus disease 2019 (COVID-19) pandemic shook the world in ways not seen since the pandemic influenza of 1918-1919. As of late August 2020, over 25 million persons had been infected, and we will see the global death toll exceed one million by the end of 2020. Both are minimum estimates. All segments of society have been drastically affected. Schools worldwide have been forced to close due to illness and absenteeism, transmission and risk to vulnerable members of the school community, and community concerns. The decision to reopen school during a pandemic will have a tremendous impact on children's safety, growth, and well-being. Not opening invites social isolation and suboptimal educational experiences, especially for youth whose computing assets and online access are limited and those with special needs. The opening has hazards as well, and the mitigation of these risks is the topic of this chapter. Opening schools requires careful considerations of benefits, risks, and precautions. Guiding principles for safety and strategic application of the principles in each educational niche are critical issues to consider during school reopening. The fundamental principles of disease control involve school-directed initiatives (physical distancing and mask use, hand/face and surface cleansing, administrative controls, engineering controls) and individual-level risk reduction approaches to maximize adherence to new guidelines. The school-initiated "top-down" approaches and the individual-level "bottom-up" approaches must be synergized, as no single method will ensure safety. We discuss how to effectively layer strategies in each educational space to increase safety. Since the vulnerability of children has been heightened during this pandemic crisis, we highlight the special considerations for mental health support that should be considered by schools. The safety principles, disease control strategies, and other critical issues discussed here will serve as a starting point for developing a safe, comprehensive, and feasible reopening plan.

A randomized clinical trial of a nurse telephone follow-up on paediatric tonsillectomy pain management and complications.

AIMS: To determine the effect of a nurse telephone follow-up on paediatric post-tonsillectomy pain intensity, complications, and use of other healthcare services. BACKGROUND: After tonsillectomy, children experience moderate-to-severe pain for days. Parents tend to give insufficient analgesia, with resulting increases in pain and postoperative complications. In adults, nurse telephone follow-up for ambulatory surgeries reduces postoperative pain. DESIGN: The study design was a randomized clinical trial. METHODS: In this trial, children aged 4-12 years undergoing elective tonsillectomy in June-October 2010 were assigned to a nurse telephone follow-up with parents on postoperative days 1, 3, 5 and 10, or standard care with no follow-up but data collection. Outcomes included pain intensity, analgesics administered, complications, and healthcare use. RESULTS: Of 45 participants, the intervention group (n = 24) received more analgesics on postoperative days 1 and 3, increased their fluid intake at days 1 and 3, but had more constipation at day 3 than the control group (n = 21). There was no significant difference regarding pain intensity or use of healthcare resources. CONCLUSION: Nurse telephone follow-up was beneficial for some pain management and prevention of complications, although better analgesic treatments are needed. The intervention was simple, safe, and appreciated by parents.

Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis.

Amyloid beta-peptide (Abeta) is a major constituent of senile plaques in Alzheimer's disease (AD). Neurotoxicity results from the conformational transition of Abeta from random-coil to beta-sheet and its oligomerization. Among a series of ionic compounds able to interact with soluble Abeta, Tramiprosate (3-amino-1-propanesulfonic acid; 3APS; Alzhemedtrade mark) was found to maintain Abeta in a non-fibrillar form, to decrease Abeta(42)-induced cell death in neuronal cell cultures, and to inhibit amyloid deposition. Tramiprosate crosses the murine blood-brain barrier (BBB) to exert its activity. Treatment of TgCRND8 mice with Tramiprosate resulted in significant reduction (approximately 30%) in the brain amyloid plaque load and a significant decrease in the cerebral levels of soluble and insoluble Abeta(40) and Abeta(42) (approximately 20-30%). A dose-dependent reduction (up to 60%) of plasma Abeta levels was also observed, suggesting that Tramiprosate influences the central pool of Abeta, changing either its efflux or its metabolism in the brain. We propose that Tramiprosate, which targets soluble Abeta, represents a new and promising therapeutic class of drugs for the treatment of AD.

Mapping genetic modulators of amyloid plaque deposition in TgCRND8 transgenic mice.

Alzheimer's disease (AD) is a complex disorder for which various in vivo models exist. The TgCRND8 mouse, transgenic for the human amyloid precursor protein, is an aggressive early onset model of brain amyloid deposition. Preliminary studies revealed that when the transgene is expressed on an A/J genetic background, these mice not only survive longer but also deposit less parenchymal amyloid-beta (Abeta) peptides as compared to those on a C57BL/6 background. We performed a genome-wide study of an F2 intercross between TgCRND8 on an A/J background and C57BL/6 mice, to identify genetic modulators of amyloid accumulation and deposition. We identified four highly significant QTLs that together account for 55% of the phenotypic variance in the number of plaques (Thioflavin S). QTLs were found on the distal part of chromosome 4 with an LOD score of 8.1 at D4Mit251, on chromosome 11 with an LOD score of 5.5 at D11Mit242, on chromosome 9 with an LOD score of 5.0 at D9Mit336 and on the proximal part of chromosome 8 with an LOD score of 4.5 at D8Mit223. A/J alleles at these loci are protective and all decreased the amount of Abeta deposition. Interestingly, the QTL on chromosome 11 is also significantly linked to the levels of brain Abeta(42) and Abeta(40). Although these QTLs do not control the levels of plasmatic Abeta, other regions on chromosomes 1 and 6 show significant linkage. Further characterization of these QTL regions may lead to the identification of genes involved in the pathogenesis of AD.

Rapid induction of the intrinsic apoptotic pathway by L-glutamine starvation.

While the amino acid L-glutamine is known to play a role in the survival of several cell types, the underlying molecular mechanisms are still poorly defined. We show in this report that L-glutamine starvation rapidly triggered apoptosis in Sp2/0-Ag14 hybridoma cells. This process involved the activation of both caspases-9 and -3, suggesting that L-glutamine deprivation initiated an intrinsic apoptotic pathway in Sp2/0-Ag14 cells. Supporting this idea, the cytosolic release of the mitochondrial proteins SMAC/DIABLO and cytochrome c (Cyt c) was observed, with an initial limited leakage occurring during the first 30 min of L-glutamine deprivation, followed by a greater release after 60 min. The latter occurred simultaneously with the translocation of the pro-apoptotic protein Bax to the mitochondria. Finally, a decline in XIAP levels and the activation of caspases-3 and -9 were observed. Thus, L-glutamine deprivation of Sp2/0-Ag14 cells rapidly triggers intracellular events, which target the mitochondria, leading to the cytosolic release of apoptogenic factors, the activation of caspases-9 and -3, and the commitment to the death program. This work introduces the Sp2/0Ag14 hybridoma as a unique model for the study of the molecular events underlying the pro-survival function of L-glutamine.

Inflammation occurs early during the Abeta deposition process in TgCRND8 mice.

Alzheimer's disease (AD) is characterized by a progressive cognitive decline leading to dementia and involves the deposition of amyloid-beta (Abeta) peptides into senile plaques. Other neuropathological features that accompany progression of the disease include a decrease in synaptic density, neurofibrillary tangles, dystrophic neurites, inflammation, and neuronal cell loss. In this study, we report the early kinetics of brain amyloid deposition and its associated inflammation in an early onset transgenic mouse model of AD (TgCRND8) harboring the human amyloid precursor protein gene with the Indiana and Swedish mutations. Both diffuse and compact plaques were detected as early as 9-10 weeks of age. Abeta-immunoreactive (Abeta-IR) plaques (4G8-positive) appeared first in the neocortex and amygdala, then in the hippocampal formation, and lastly in the thalamus. Compact plaques (ThioS-positive) with an amyloid core were observed as early as diffuse plaques were detected, but in lower numbers. Amyloid deposition increased progressively with age. The formation of plaques was concurrent with the appearance of activated microglial cells and shortly followed by the clustering of activated astrocytes around plaques at 13-14 weeks of age. This TgCRND8 mouse model allows for a rapid, time-dependent study of the relationship between the fibrillogenic process and the inflammatory response during the brain amyloidogenic process.

Screening and treatment of anxiety disorders in pregnant and lactating women.

Untreated anxiety disorders during pregnancy and the postpartum period may pose significant risks to the unborn fetus and interfere with a mother's ability to properly care for her newborn child. As the symptoms of anxiety disorders are often similar to those found in pregnancy, careful screening for anxiety disorders in pregnant women is essential. For women suffering from anxiety disorders during or after pregnancy, safe and effective treatment is needed. In this article, suggestions are offered for thorough assessment of anxiety disorders in pregnant and breastfeeding women. Treatment options are discussed with an emphasis on pharmacologic and cognitive-behavioral treatment.