Project description:BackgroundCerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes.MethodsThis was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score.ResultsOne hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05).ConclusionsCommon pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.
Project description:Successful epidemic modeling requires understanding the implicit feedback control strategies used by populations to modulate the spread of contagion. While such strategies can be replicated with intricate modeling assumptions, here we propose a simple model where infection dynamics are described by a three parameter feedback policy. Rather than model individuals as directly controlling the contact rate which governs the spread of disease, we model them as controlling the contact rate's derivative, resulting in a dynamic rather than kinematic model. The feedback policy used by populations across the United States which best fits observations is proportional-derivative control, where learned parameters strongly correlate with observed interventions (e.g., vaccination rates and mobility restrictions). However, this results in a non-zero "steady-state" of case counts, implying current mitigation strategies cannot eradicate COVID-19. Hence, we suggest making implicit policies a function of cumulative cases, resulting in proportional-integral-derivative control with higher potential to eliminate COVID-19.
Project description:BackgroundCOVID-19 poses a risk to the endoscopic skull base surgeon. Significant efforts to improving safety have been employed, including the use of personal protective equipment, preoperative COVID-19 testing, and recently the use of a modified surgical mask barrier.ObjectiveTo reduce the risks of pathogen transmission during endoscopic skull base surgery.MethodsThis study was exempt from Institutional Review Board approval. Our study utilizes a 3-dimensional (3D)-printed mask with an anterior aperture fitted with a surgical glove with ports designed to allow for surgical instrumentation and side ports to accommodate suction ventilation and an endotracheal tube. As an alternative, a modified laparoscopic surgery trocar served as a port for instruments, and, on the contralateral side, rubber tubing was used over the endoscrub endosheath to create an airtight seal. Surgical freedom and aerosolization were tested in both modalities.ResultsThe ventilated mask allowed for excellent surgical maneuverability and freedom. The trocar system was effective for posterior surgical procedures, allowing access to critical paramedian structures, and afforded a superior surgical seal, but was limited in terms of visualization and maneuverability during anterior approaches. Aerosolization was reduced using both the mask and nasal trocar.ConclusionThe ventilated upper airway endoscopic procedure mask allows for a sealed surgical barrier during endoscopic skull base surgery and may play a critical role in advancing skull base surgery in the COVID-19 era. The nasal trocar may be a useful alternative in instances where 3D printing is not available. Additional studies are needed to validate these preliminary findings.
Project description:PurposeObesity is a reversible risk factor for obstructive sleep apnoea (OSA). Weight loss can potentially improve OSA by reducing fat around and within tissues surrounding the upper airway, but imaging studies are limited. Our aim was to study the effects of large amounts of weight loss on the upper airway and volume and fat content of multiple surrounding soft tissues.MethodsParticipants undergoing bariatric surgery were recruited. Magnetic resonance imaging (MRI) was performed at baseline and six-months after surgery. Volumetric analysis of the airway space, tongue, pharyngeal lateral walls, and soft palate were performed as well as calculation of intra-tissue fat content from Dixon imaging sequences.ResultsAmong 18 participants (89% women), the group experienced 27.4 ± 4.7% reduction in body weight. Velopharyngeal airway volume increased (large effect; Cohen's d [95% CI], 0.8 [0.1, 1.4]) and tongue (large effect; Cohen's d [95% CI], - 1.4 [- 2.1, - 0.7]) and pharyngeal lateral wall (Cohen's d [95% CI], - 0.7 [- 1.2, - 0.1]) volumes decreased. Intra-tissue fat decreased following weight loss in the tongue, tongue base, lateral walls, and soft palate. There was a greater effect of weight loss on intra-tissue fat than parapharyngeal fat pad volume (medium effect; Cohen's d [95% CI], - 0.5 [- 1.2, 0.1], p = 0.083).ConclusionThe study showed an increase in velopharyngeal volume, reduction in tongue volume, and reduced intra-tissue fat in multiple upper airway soft tissues following weight loss in OSA. Further studies are needed to assess the effect of these anatomical changes on upper airway function and its relationship to OSA improvement.
Project description:Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.
Project description:ObjectiveTo provide a critical overview of the effect of various orthodontic and/or dentofacial orthopedic interventions on three-dimensional volumetric changes in the upper airway.Materials and methodsFour databases were searched for clinical studies concerning 3D volumetric assessments based on CBCT before and after orthodontics interventions. The quality of the studies was assessed using the quality assessment tool of the National Heart, Lung and Blood Institute. After the use of inclusion and exclusion criteria, the pre-and post-treatment volumes were used to visualize the effect of various orthodontics interventions.ResultsA total of 48 studies were included in this review and none of which were RCTs. The quality of all included studies was assessed as medium. Overall, there is a tendency for an increase in airway volumes after various orthodontic interventions, except for studies concerning extraction therapy with fixed appliances in adults, in which both increases and decreases in airway volumes have been reported.ConclusionOrthodontic treatment by growth modification and non-extraction therapy with fixed appliances, regardless of the malocclusion, generally showed positive effects on the airway volume. Orthodontic treatment in combination with extractions does not provide an unambiguous insight. A consensus on the methodology of the airway measurement and nomenclature is urgently needed in order to gain insight into the effect of different interventions on three-dimensional airway changes.Clinical relevanceVarious orthodontic treatments do not negatively influence the upper airway volume. However, extraction therapy in adults should be chosen with caution, especially in subjects belonging to a group susceptible to airway obstruction.
Project description:BackgroundMost patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA.MethodsTen obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2-10 cm H2O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred.ResultsDuring reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation.ConclusionsCompensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers.
Project description:Sleep related breathing disorders cause obstruction of the upper airway which can be alleviated by continuous positive airway pressure (CPAP) therapy, oral devices or surgical intervention. Non-surgical treatment modalities are not always accepted by patients and in order to attain successful surgical outcomes, evaluation of the upper airway is necessary to carefully select the patients who would benefit from surgery. There are numerous techniques available to assess the upper airway obstruction and these include imaging, acoustic analysis, pressure transducer recording and endoscopic evaluation. It is essential to note that the nocturnal obstructive upper airway has limited muscle control compared to the tone of the upper airway lumen during wakefulness. Thus, if one were to attempt to identify the anatomical segments contributing to upper airway obstruction in sleep related breathing disorders; it must be borne in mind that evaluation of the airway must be performed if possible when the patient is awake and asleep albeit during drug induced sleep. This fact as such limits the use of imaging techniques for the purpose. Drug induced sleep endoscopy (DISE) was pioneered at Royal National Throat, Nose and Ear Hospital, London in 1990 and initially introduced as sleep nasendoscopy. The nomenclature and the technique has been modified by various Institutions but the core value of this evaluation technique remains similar and extremely useful for identifying the anatomical segment responsible for obstructing the upper airway during sleep in patients with sleep related breathing disorders. There have been numerous controversies that have surrounded this technique but over the last two decades most of these have been addressed and it now remains in the forefront of methods of evaluating the upper airway obstruction. A variety of sedative agents and different grading systems have been described and efforts to unify various aspects of the technique have been made. This article will look at its usefulness and advantages and will discuss some important contributions made to the field of evaluation of the upper airway using DISE.