Excessive Use of Benzodiazepines Is a Risk Factor for Endotracheal Intubation in Children Who Present to Emergency With Prehospital Status Epilepticus.

OBJECTIVES: There is lack of evidence-based information on the use and timing of endotracheal intubation (ETI) in children with prehospital status epilepticus (SE). METHODS: The aim of this study was to investigate ETI use, timing, risk factors, and outcomes in children presenting to a single-center children's emergency (CE) with prehospital SE, over a 5-year period. RESULTS: A total of 118 events involving children presenting to CE with ongoing prehospital SE were included, and 39% (46/118) of the events required ETI. The most common indication for ETI was respiratory depression. The median time to intubation after arrival at CE was 20.0 minutes (1-155 minutes). Risk factors associated with ETI use include the administration of more than 2 benzodiazepines (26.1% vs 4.2%, P < 0.001) and the use of second- or third-line antiepileptic therapy ( P < 0.001). The use of more than 2 doses of benzodiazepines was found in 12.7% (15/118) of the patients. In patients who received excessive benzodiazepines, 87% (13/15) of them required intubation. CONCLUSIONS: Excessive use of benzodiazepine was found to be a main risk factor for ETI in patients with prehospital SE. Avoidance of the excessive use of benzodiazepines and adhering to clinical management guidelines may reduce the risk for ETI in the CE. The best approach to airway management in children with prehospital SE is lacking and urgently needed.

Functional Adaptation of LPS-affected Dentoalveolar Fibrous Joints in Rats.

INTRODUCTION: The functional interplay between cementum of the root and alveolar bone of the socket is tuned by a uniquely positioned 70-80 µm wide fibrous and lubricious ligament in a dentoalveolar joint (DAJ). In this study, structural and biomechanical properties of the DAJ, periodontal ligament space (PDL-space also known as the joint space), alveolar bone of the socket, and cementum of the tooth root that govern the biomechanics of a lipopolysaccharide (LPS)-affected DAJ were mapped both in space and time. METHODS: The hemi-maxillae from 20 rats (4 control at 6 weeks of age, 4 control and 4 LPS-affected at 12 weeks of age, 4 control and 4 LPS-affected at 16 weeks of age) were investigated using a hybrid technique; micro-X-ray computed tomography (5 µm resolution) in combination with biomechanical testing in situ. Temporal variations in bone and cementum volume fractions were evaluated. Trends in mineral apposition rates (MAR) in additional six Sprague Dawley rats (3 controls, 3 LPS-affected) were revealed by transforming spatial fluorochrome signals to functional growth rates (linearity factor - RW) of bone, dentin, and cementum using a fast Fourier transform on fluorochrome signals from 100-µm hemi-maxillae sections. RESULTS: An overall change in LPS-affected DAJ biomechanics (a 2.5-4.5X increase in tooth displacement and 2X tooth rotation at 6 weeks, no increase in displacement and a 7X increase in rotation at 12 weeks; 27% increase in bone effective strain at 6 weeks and 11% at 12 weeks relative to control) was associated with structural changes in the coronal regions of the DAJ (15% increase in PDL-space from 0 to 6 weeks but only 5% from 6 to 12 weeks compared to control). A significant increase (p < 0.05) in PDL-space between ligated and age-matched control was observed. The bone fraction of ligated at 12 weeks was significantly lower than its age-matched control, and no significant differences (p > 0.05) between groups were observed at 6 weeks. Cementum in the apical regions grew faster but nonlinearly (11% and 20% increase in cementum fraction (CF) at 6 and 12 weeks) compared to control. Alveolar bone revealed site-specific nonlinear growth with an overall increase in MAR (108.5 µm/week to 126.7 µm/week after LPS treatment) compared to dentin (28.3 µm/week in control vs. 26.1 µm/week in LPS-affected) and cementum (126.5 µm/week in control vs. 119.9 µm/week in LPS-affected). A significant increase in CF (p < 0.05) in ligated specimens was observed at 6 weeks of age. CONCLUSIONS: Anatomy-specific responses of cementum and bone to the mechano-chemo stimuli, and their collective temporal contribution to observed changes in PDL-space were perpetuated by altered tooth movement. Data highlight the "resilience" of DAJ function through the predominance of nonlinear growth response of cementum, changes in PDL-space, and bone architecture. Despite the significant differences in bone and cementum architectures, data provided insights into the reactionary effects of cementum as a built-in compensatory mechanism to reestablish functional competence of the DAJ. The spatial shifts in architectures of alveolar bone and cementum, and consequently ligament space, highlight adaptations farther away from the site of insult, which also is another novel insight from this study. These adaptations when correlated within the context of joint function (biomechanics) illustrate that they are indeed necessary to sustain DAJ function albeit being pathological.

Vagus nerve stimulation for treatment of drug-resistant epilepsy: a systematic review and meta-analysis.

To analyze the efficacy and safety of high-frequency VNS versus control (low-frequency VNS or no VNS) in patients with DRE using data from randomized controlled trials (RCTs). An electronic literature search was conducted on PubMed, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL); 12 RCTs reporting seizure frequency or treatment response in studies containing a high-frequency VNS treatment arm (conventional VNS or transcutaneous VNS [tVNS]) compared to control (low-frequency VNS or no VNS) were included. Seizure frequency, treatment response (number of patients with ≥ 50% reduction in seizure frequency), quality of life (QOL), and adverse effects were analyzed. Seizure frequency was reported in 9 studies (718 patients). Meta-analysis with random-effects models favored high-frequency VNS over control (standardized mean difference = 0.82, 95%-CI = 0.39-1.24, p < .001). This remained significant for subgroup analyses of low-frequency VNS as the control, VNS modality, and after removing studies with moderate-to-high risk of bias. Treatment response was reported in 8 studies (758 patients). Random-effects models favored high-frequency VNS over control (risk ratio = 1.57, 95%-CI = 1.19-2.07, p < .001). QOL outcomes were reported descriptively in 4 studies (363 patients), and adverse events were reported in 11 studies (875 patients). Major side effects and death were not observed to be more common in high-frequency VNS compared to control. High-frequency VNS results in reduced seizure frequency and improved treatment response compared to control (low-frequency VNS or no VNS) in patients with drug-resistant epilepsy. Greater consideration for VNS in patients with DRE may be warranted to decrease seizure frequency in the management of these patients.

Biomechanical pathways of dentoalveolar fibrous joints in health and disease.

Spatial and temporal adaptations within periodontal tissues and their interfaces result from functional loads. Functional loads can be physiologic and/or pathologic in nature. The prolonged effect of these loads can alter the overall biomechanics of a dentoalveolar fibrous joint (dentoalveolar joint) by changing the form of the tooth root and its socket. This "sculpting" of the tooth root and alveolar bony socket is a consequence of several mechano-biological changes that occur within the periodontal complex of a load-bearing dentoalveolar joint. These include changes in biochemical expressions, structure, elemental composition, and mechanical properties of alveolar bone, the underlying tissues of the roots of teeth, and their interfaces. These physicochemical changes in tissues continue to prompt mechano-responsive biochemical activities at the attachment sites of periodontal ligament (soft) with bone (hard), and ligament with cementum (hard), which are the entheses of a load-bearing dentoalveolar joint. Forces at soft-hard tissue attachment sites between disparate materials with different stiffness values theoretically generate strain singularities or discontinuities. These discontinuities under prolonged functional loading increase the probability for failure to occur specifically at the enthesial zones. However, in a normal dentoalveolar joint, gradual stiffness gradients exist from ligament to bone, and from ligament to cementum. The gradual transitions in stiffness from softer ligament (lower stiffness) to harder bone or cementum (higher stiffness) or vice versa optimize tissue and interfacial strains. Optimization of tissue and ligament-enthesial physical and chemical properties facilitates transmission of cyclic forces of varying magnitudes and frequencies that collectively maintain the overall biomechanics of a dentoalveolar joint. The objectives of this review are 3-fold: (i) to illustrate physicochemical adaptations at the periodontal ligament entheses of a human periodontal complex affected by subgingival calculus; (ii) to demonstrate how to "program" the hallmarks of periodontitis in small-scale vertebrates in vivo to generate spatiotemporal maps of physicochemical adaptations in a diseased dentoalveolar joint; and (iii) to correlate dentoalveolar joint biomechanics in healthy and diseased states to spatiotemporal maps of physicochemical adaptations within respective periodontal tissues. This interdisciplinary approach demonstrates that physicochemical adaptations within periodontal tissues using the mechanics of materials (tissue mechanics), materials science (tissue composition), and mechano-biology (matrix molecules) can help explain the mechano-adaptation of dentoalveolar joints in normal and diseased functional states. Multiscale biomechanics and mechano-biology approaches can provide insights into the functional competence of a diseased relative to a normal dentoalveolar joint. Insights gathered from interdisciplinary and multiscale biomechanics approaches include the following: (i) physiologic loads related to chewing maintain a balance between mineral-forming and-resorbing biochemical cellular events, resulting in gradual stiffness gradients at the periodontal ligament entheses, and, in turn, sustain the overall biomechanics of a normal "healthy" dentoalveolar joint; (ii) pathologic loads resulting from tissue degradation and physical changes to the periodontal complex promote an abrupt stiffness gradient at the periodontal ligament entheses. The shift from gradual to an abrupt stiffness gradient could prompt a shift in the biochemical cascades, exacerbate mechano-responsive biochemical expressions at periodontal ligament entheses farther away from the site of insult, and culminate in joint degradation; (iii) sustained pathologic function on periodontally diseased joints exacerbates degradation of periodontal ligament entheses providing insights into "rescue therapy", such as the use of an adequate "mechanocal dose" to regain joint function; and (iv) spatiotemporal maps of changes in biochemical expressions, and physicochemical properties of strain-dominated affected sites, including the periodontal ligament entheses, can guide anatomy-specific therapeutics for tissue regeneration and/or disease control with the purpose of regaining dentoalveolar joint function. Modulation of occlusal loads could minimize disease progression and potentially assist in regaining functional attachment of ligament to bone and/or ligament to cementum of the dentoalveolar joint. Elucidating mechanisms that drive the breakdown of the functionally active periodontal complex burdened with microbes will provide the required critical insights into regenerative medicine and/or biomimetic approaches that would facilitate rescue/regain of dentoalveolar joint function.

Acute hemichorea in a young type 1 diabetic.

Purpose/Aim: Acute movement disorder is an uncommon presenting symptom in patients with diabetes mellitus. We report a 20-year-old lady with poorly controlled type 1 diabetes, who presented with acute hemichorea and was found to have two rare diabetes-related central nervous complications of diabetic striatopathy and severe moyamoya disease (MMD).Materials and methods: She was treated with aggressive glycemic control; clonazepam and tetrabenazine as well as aspirin stroke prophylaxis for her MMD with resolution of her chorea 3 months later. She subsequently underwent cerebral revascularization surgery for her MMD.Results: This case highlights the possible differentials of acute chorea in diabetic patients and explores the pathophysiological mechanisms that may underlie both conditions in patients with type 1 diabetes.Conclusion: We recommend performing both magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) brain for comprehensive evaluation of diabetic patients with new onset chorea. Prompt and accurate diagnosis is crucial as it guides prognostication and treatment strategies.

Characterizing Factors Associated With Differences in FGF19 Blood Levels and Synthesis in Patients With Primary Bile Acid Diarrhea.

OBJECTIVES: Chronic diarrhea caused by primary bile acid diarrhea (PBAD) is a common condition. We have previously shown PBAD is associated with low fasting serum levels of the ileal hormone, fibroblast growth factor 19 (FGF19). FGF19 is a negative regulator of hepatic bile acid synthesis and is stimulated by farnesoid X receptor agonists, which produce symptomatic improvement in PBAD. We aimed to assess possible causes for low serum FGF19 in patients with PBAD. METHODS: Patients with PBAD, defined by reduced (75)Se-labelled homocholic acid taurine (SeHCAT) retention, and idiopathic diarrhea controls had measurements of fasting lipids and fasting/post-prandial FGF19 serum profiles. Specific functional variants in candidate genes were investigated in exploratory studies. In further groups, basal and bile acid-stimulated transcript expression was determined in ileal biopsies and explant cultures by quantitative PCR. RESULTS: FGF19 profiles in PBAD patients included low fasting and meal-stimulated responses, which were both strongly correlated with SeHCAT. A subgroup of 30% of PBAD patients had fasting hypertriglyceridemia and higher FGF19. No clear significant differences were found for any genetic variant but there were borderline associations with FGFR4 and KLB. SeHCAT retention significantly correlated with the basal ileal transcript expression of FGF19 (rs=0.59, P=0.03) and apical sodium-dependent bile acid transporter (ASBT) (rs=0.49, P=0.04), and also with the degree of stimulation by chenodeoxycholic acid at 6 h for transcripts of FGF19 (median 184-fold, rs=0.50, P=0.02) and ileal bile acid binding protein (IBABP) (median 2.2-fold, rs=0.47, P=0.04). Median stimulation of FGF19 was lower in patients with SeHCAT retention <10% (P=0.01). CONCLUSIONS: These studies demonstrate a complex, multifactorial etiology of PBAD, including impairments in ileal FGF19 expression and responsiveness.

Access to dental care and caries experience among children with cerebral palsy: a Singapore experience.

INTRODUCTION: Cerebral palsy (CP) is one of the most severe childhood neurodevelopmental disabilities resulting from non-progressive insult to the developing brain. We aimed to report our experience regarding dental visit attendance, caries prevalence and factors affecting dental access in children with CP in Singapore. METHODS: Patients diagnosed with CP who were born in or after 1994 were included in this study. We reviewed the data of all 151 patients recruited under the CP Registry in Singapore (SingCPR) from September 2017 to May 2020. The SingCPR was launched in September 2017 to assist in future planning of services and resources for CP in Singapore. RESULTS: The mean age of the patients was 7.8 years, with the interquartile range being 3 years and 8 months-10 years and 10 months. Only 41.7% reported a visit to the dentist ever, with 25.4% reporting presence of dental caries. Age was the only statistically significant factor influencing access to dental care. None of the children less than 2 years old ever received any dental care, and 20% of the children with CP aged 2-6 years had received dental care before. Age range with the highest percentage of dental visits was 7-12 years, with up to 44.0% having ever received dental care. We believe the prevalence of dental caries was underreported as many children did not receive any dental care and therefore may have undetected dental caries. CONCLUSION: Dental care in children with CP should be advocated early for prevention and detection of caries.

Mild Neurological Manifestations Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Children During the Omicron Wave in Singapore: A Retrospective Cohort Review.

BACKGROUND: Neurological complications with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant have been reported in adults; however, there are little data in the pediatric population. We aimed to report on the prevalence and clinical characteristics of children with neurological symptoms during the SARS-CoV-2 omicron wave. METHODS: This was a single-center, retrospective cohort review of children (<18 years old) hospitalized for SARS-CoV-2 infection from December 2, 2021, to June 30, 2022. RESULTS: During the study period, 455 children (mean age 4.8 years, range 0.67 to 18, male 58.9%) were hospitalized with SARS-CoV-2 infection. A total of 108 (23.7%) children experienced neurological symptoms; most common were seizures (62.0%), headaches (32.4%) and giddiness (14.8%). Seizures included febrile seizures (64.1%), acute symptomatic seizures (17.9%), and breakthrough seizures in known epileptics (17.9%). Children with neurological manifestations were older (7.3 vs 4.0 years, P < 0.00001), more likely to have underlying epilepsy (9.3% vs 1.2%, P = 0.0002) or neurodevelopmental disorders (17.6% vs 1.7%, P < 0.00001), and presented earlier in their illness (2.1 vs 2.8 days, P < 0.00001), compared with those without neurological manifestations. Neurological symptoms fully resolved in all but one patient at discharge. There were no mortalities and no difference in duration of hospitalization (3.1 vs 3.7 days, P = 0.5) between the groups. CONCLUSIONS: One in four hospitalized children with SARS-CoV-2 infection when omicron variant was dominant experienced mild neurological symptoms. Overall risk factors for neurological symptoms associated with SARS-CoV-2 included older age, pre-existing febrile seizures/epilepsy and neurodevelopmental disorders.

Outcomes after surgical revascularization for adult Moyamoya disease: A Southeast Asian tertiary centre experience.

There are numerous studies on the natural history and outcomes of adult Moyamoya disease (MMD) in the literature, but limited data from Southeast Asian cohorts. Hence, we aimed to retrospectively review the clinical characteristics and outcomes after surgical revascularization for adult MMD in our Southeast Asian cohort. Patients were included if they were above 18 years old at the first surgical revascularization for MMD, and underwent surgery between 2012 and 2022 at the National University Hospital, Singapore. The outcomes were transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, and all-cause mortality during the postoperative follow-up period. In total, 26 patients who underwent 27 revascularization procedures were included. Most patients were of Chinese ethnicity, and the mean (SD) age at the time of surgery was 47.7 (12.6) years. The commonest clinical presentation was intracerebral hemorrhage, followed by TIA and ischemic stroke. Direct revascularization with superficial temporal artery-middle cerebral artery (STA-MCA) bypass was the most common procedure (24/27 surgeries, 88.9 %). The mean (SD) follow-up duration was 4.2 (2.5) years, during which the overall incidence of postoperative TIA/stroke was 25.9 % (7/27 surgeries), with most cases occurring within 7 days postoperatively. There were no mortalities during the postoperative follow-up period. Risk factors for 30-day postoperative TIA/stroke included a higher number of TIAs/strokes preoperatively (p = 0.044) and indirect revascularization (p = 0.028). Diabetes mellitus demonstrated a trend towards an increased risk of 30-day postoperative TIA/stroke, but this was not statistically significant (p = 0.056). These high-risk patients may benefit from more aggressive perioperative antithrombotic and hydration regimens.

Health practices, behaviours and quality of life of low-income preschoolers: A community-based cross-sectional comparison study in Singapore.

Introduction: Children from low-income (LI) families often suffer from poor health, with sub-optimal health practices. This cross-sectional study examined the differences in health habits and health-related quality of life (HRQoL) of LI preschool children compared to non-low-income preschool peers (PPG). Method: Using data from the social-health Circle of Care-Health Development Screening Programme (CoC-HDSP) in Singapore, 118 LI children and 304 PPG children aged 18 months to 6 years old and their families were recruited from 13 government-funded preschools. Health practices examined included screen time habits, sleep, nutrition, dental health and the children's HRQoL using PedsQL 4.0 Generic Core Scales. Results: Majority of the children were aged 4-6 years in kindergarten 1 and 2. There were more Malay children in the LI than the PPG (61.9% versus [vs] 29.3%, P<0.001). Low-income children were more likely to have lower-educated parents (P<0.001). The completed vaccination rate in the LI group was lower than those in PPG (84.7% vs 98.0%, P<0.001). More in the LI group utilised emergency services for acute illnesses (P<0.05). Fewer LI children had ever visited a dentist (47.4% vs 75.4%, P<0.001), and more LI children consumed sweetened drinks daily (33.3% vs 8.6%, P<0.001). The LI group reported poorer-quality sleep (48.3% vs 27.2%, P<0.001), though both groups exceeded the daily recommended screen viewing duration. The LI group scored higher in the social (mean 92.4±12.2 vs 84.3±15.3, P<0.001) and emotional (mean 85.2±15.1 vs 76.6±17.3, P<0.001) domains of the PedsQL 4.0 when compared to PPG. Conclusion: Low-income children have poorer health practices, receive less preventive paediatric care, and utilise more emergency services for acute illnesses. These findings are important for developing interventions that work towards improving the health of LI children.

An online community peer support intervention to promote COVID-19 vaccine information among essential workers: a randomized trial.

INTRODUCTION: Vaccine hesitancy is still rampant in the United States, including health care personnel. Vaccination of frontline essential workers (e.g. health care workers) is very important, especially during a pandemic. We tested the efficacy of a 4-week online, peer-led intervention (Harnessing Online Peer Education) to promote requests for COVID-19 vaccine information among essential workers. METHODS: Participants (N = 120) and peer leaders (N = 12) were recruited through online advertisements from July 23 to August 20, 2021. Eligibility criteria included: 18 years or older, U.S. resident, English speaker, part of phase 1a or 1 b of COVID-19 vaccine rollout (e.g. frontline essential workers), hadn't received a COVID-19 vaccine but able to receive one. This was a parallel assignment randomised trial. STATA was used to create a randomisation using a random number generator so that all possible assignments of participants and peer leaders to groups were equally likely. Participants were randomly assigned to intervention or control arms that consisted of two private, hidden Facebook groups, each with 30 participants. Peer leaders were randomly assigned to an intervention group, each with six peer leaders. Participants in the intervention arm were randomly assigned to three peer leaders. Participants were blinded after assignment. Peer leaders were tasked with reaching out to their assigned participants at least three times each week. Participants completed a baseline and a post intervention survey. The study is registered on ClinicalTrials.org under identifier NCT04376515 and is no longer recruiting. This work was supported by the NIAID under grant 5R01AI132030-05. RESULTS: A total of 101 participants analysed (50 intervention and 51 control). Six people in the intervention group and 0 people in the control group requested vaccine information. Ten people in the intervention group and six people in the control group provided proof of vaccination. The odds of requesting vaccine information in the intervention group was 13 times that in the control group (95% confidence interval: (1.5, 1772), p-value = 0.015). Thirty-seven participants in the intervention group and 31 in the control group were engaged at some point during the study. CONCLUSIONS: Results suggest peer-led online community groups may help to disseminate health information, aid public health efforts, and combat vaccine hesitancy. Key MessagesThe odds of requesting vaccine information was 13 times in the intervention group.Peer-led online communities may help to disseminate information and aid public health efforts to combat vaccine hesitancy.

Design of a compliant, stabilizing wrist mechanism for a pediatric hand exoskeleton.

Children affected by hand impairment due to cerebral palsy or stroke experience serious difficulties when performing activities of daily life (ADL), which reduces their quality of life and development. Wearable robots such as hand exoskeletons have been proposed to support people with hand impairment in therapy as well as daily tasks. While numerous actuated wearable robots have been developed, few designs support both fingers and wrist function, despite being mutually relevant for reach-to-grasp tasks. A recent feasibility study investigating the use of PEXO, a lightweight and fully wearable pediatric hand exoskeleton, showed that a wrist fixed in a slightly extended position may limit the user's ability to reach and grasp during ADL and restrict the user group. These insights and further interactions with clinicians inspired a novel design of PEXO that features an additional degree of freedom in the wrist. In this paper, we present a compliant wrist mechanism extending the existing leaf spring finger mechanism of the device. The novel design provides both wrist motion capability of 60° in flexion and extension and wrist stabilization at the same time while actively supporting finger motion. Preliminary results suggest that the adjustability in the wrist enables a larger variety of grasping gestures. The implemented wrist support has the potential to allow for a more versatile use of PEXO and increase the potential target user group.

Predictors of Favorable Neurologic Outcomes in a Territory-First Extracorporeal Cardiopulmonary Resuscitation Program.

Extracorporeal cardiopulmonary resuscitation (ECPR) is an advanced resuscitation method that has been associated with better outcomes after cardiac arrest compared with conventional cardiopulmonary resuscitation. This is a retrospective analysis of all patients who received ECPR for cardiac arrest in Hong Kong's first ECPR program from 2012 to 2020. The primary outcome was favorable neurologic outcome at 3 months. A new risk prediction model was developed and its performance was compared with published risk scores. One-hundred two patients received ECPR and 19 (18.6%) patients survived with favorable neurologic outcome. Having a shockable rhythm was the strongest predictor of favorable neurologic outcome in multivariate analysis (odds ratio, 9.64; 95% confidence interval [CI], 1.49 to 62.30; P = 0.017). We developed a simple model with three parameters for the prediction of favorable neurologic outcomes - presence of shockable rhythm, mean arterial pressure after extracorporeal membrane oxygenation, and the Acute Physiology And Chronic Health Evaluation IV score, with an area under receiver operating characteristic curve of 0.85 (95% CI, 0.77 to 0.94). In Hong Kong's first ECPR program, 18.6% patients survived with favorable neurologic outcomes, and having a shockable rhythm at presentation was the strongest predictor. Risk scores are useful in predicting important patient outcomes and should be included in clinical decision-making for patients who received ECPR.