Paediatric acute care: Highlights from the Paediatric Acute Care–Advanced Paediatric Life Support Conference,Hobart, 2018

The Paediatric Acute Care Conference (PACC) is an annual conference organised by APLS Australia to advance paediatric acute care topics for clinicians in pre‐hospital medicine, EDs, acute paediatrics, intensive care and anaesthesia. The PACC 2018 was held in Hobart, Tasmania. We provide a summary of some of the presentations.     

Linking chronic stress to insomnia symptoms in older adults: The role of stress co-occurrence during the pandemic

Studies examining the associations of chronic stressors with sleep health in older adults have shown conflicting results. While the COVID-19 pandemic increased perceived stress at the population level, less is known about chronic stressors experienced by older adults in the context of the COVID-19 pandemic and its impact on sleep health in an aging population. This study aims to examine the association of older adults' chronic stress with insomnia symptoms during the first year of the COVID-19 pandemic. A cross-sectional analysis was performed using early-release COVID-19 data from the Health and Retirement Study. Data on chronic stressors and insomnia symptoms in older adults (N = 2021; mean age = 68.8) were examined. Co-occurrence network analysis, latent class analysis, Rao–Scott χ² tests, and multivariable logistic regression were used to characterize the co-occurrence of chronic stressors and associations with insomnia symptoms. The most common co-occurring chronic stressors during the first year of the COVID-19 pandemic were self-health issues, family-health issues, and financial stress. Older adults experiencing frequent stress co-occurrence had 91% higher odds of difficulty initiating sleep (p < 0.001), 40% higher odds of frequent nocturnal awakening (p = 0.028), and 83% higher odds of nonrestorative sleep (p < 0.001). However, adjustment for health risk factors and COVID-19 concerns attenuated the effects, leaving strongest association for difficulty initiating sleep (odds ratio = 1.51, p = 0.010). Frequent stress co-occurrence plays an important role linking chronic stress to insomnia symptoms in an aging population. Ongoing research is needed to examine the lingering effects of frequent stress co-occurrence on older adults' sleep health in the post COVID-19 era.     

The price of pain in chronic rhinosinusitis

Background

Chronic rhinosinusitis (CRS) is associated with productivity losses exceeding US$13 billion annually. Although pain is well known to significantly affect patient productivity in other diseases, its economic impact on CRS‐related lost productivity has not been examined. The objective of this study was to determine whether CRS‐related facial pain correlates with lost productivity in patients with CRS.

Methods

Seventy patients with CRS were enrolled in a cross‐sectional investigation. Patients with a history of systemic inflammatory disease, ciliary dysfunction, chronic pain syndromes, migraines, and fibromyalgia were excluded. Pain was measured using the Brief Pain Inventory Short Form (BPI‐SF) and the Short‐Form McGill Pain Questionnaire (SF‐MPQ). Presenteeism, absenteeism and lost work, and household and overall productivity were assessed. Regression analysis was performed to assess potential confounders, including depression.

Results

Pain as measured with BPI‐SF and SF‐MPQ total scores correlated with all domains of productivity losses. Overall, lost productivity was significantly correlated with pain (R range, 0.354‐0.485; p < 0.001). Presenteeism (reduced work efficiency) had the highest correlation with all of the overall pain scores (R range, ?0.366 to ?0.515; p < 0.001). Lost household productivity time was the least affected by pain (R range, 0.267‐0.389; p < 0.05). These correlations remained statistically significant after regression analysis, which accounted for depression (p < 0.05).

Conclusion

A significant correlation exists between CRS‐related facial pain and productivity losses in patients with CRS that is independent of depression. Facial pain has the strongest correlation with presenteeism, which is the main driver of productivity losses and indirect costs associated with CRS.

     

A murine model of dual infection with cytomegalovirus and Pneumocystis carinii: effects of virus-induced immunomodulation on disease progression

Despite the use of antimicrobial prophylaxis, cytomegalovirus (CMV) and Pneumocystis carinii (PC) pneumonia (PCP) are both leading causes of morbidity and mortality in immunocompromised patients. It has previously been reported that CMV infection modulates host immune responses with a variety of mechanisms which include the suppression of helper T cell functions and antigen presenting cell (APC) functions, both of which are critical for PCP resolution. However, the mechanisms of these interactions and other possible immune regulatory effects are not clearly understood. In this study, we investigated the impact of murine CMV (MCMV) induced immunomodulation on the progression of PCP in a co-infection model. Initial results show that dually infected mice had evidence of more severe PC disease, which include a greater loss of body weight, an excess lung PC burden and delayed clearance of PC from lungs, compared to mice with PC infection alone. At day 7 post-infection, dually infected mice had reduced numbers of MHC-II expressing cells in the lung interstitium and lymph nodes and reduced migration of CD11c+ cells to both the tracheobronchial lymph nodes and alveolar spaces. Dual infected mice showed elevated numbers of specific CD8 responses concomitant with a decrease in activated CD4+ T cells in both the lymph nodes and in alveolar spaces when compared to mice infected with MCMV alone. These data suggest that MCMV infection inhibits the immune responses generated against PC which contribute to the delayed clearance of the organism.     

Structural basis for cofactor-independent dioxygenation of N-heteroaromatic compounds at the α/β-hydrolase fold

Enzymatic catalysis of oxygenation reactions in the absence of metal or organic cofactors is a considerable biochemical challenge. The CO-forming 1-H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) from Arthrobacter nitroguajacolicus Rü61a and 1-H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase (QDO) from Pseudomonas putida 33/1 are homologous cofactor-independent dioxygenases involved in the breakdown of N-heteroaromatic compounds. To date, they are the only dioxygenases suggested to belong to the α/β-hydrolase fold superfamily. Members of this family typically catalyze hydrolytic processes rather than oxygenation reactions. We present here the crystal structures of both HOD and QDO in their native state as well as the structure of HOD in complex with its natural 1-H-3-hydroxy-4-oxoquinaldine substrate, its N-acetylanthranilate reaction product, and chloride as dioxygen mimic. HOD and QDO are structurally very similar. They possess a classical α/β-hydrolase fold core domain additionally equipped with a cap domain. Organic substrates bind in a preorganized active site with an orientation ideally suited for selective deprotonation of their hydroxyl group by a His/Asp charge-relay system affording the generation of electron-donating species. The “oxyanion hole” of the α/β-hydrolase fold, typically employed to stabilize the tetrahedral intermediate in ester hydrolysis reactions, is utilized here to host and control oxygen chemistry, which is proposed to involve a peroxide anion intermediate. Product release by proton back transfer from the catalytic histidine is driven by minimization of intramolecular charge repulsion. Structural and kinetic data suggest a nonnucleophilic general-base mechanism. Our analysis provides a framework to explain cofactor-independent dioxygenation within a protein architecture generally employed to catalyze hydrolytic reactions.