Reducing asthma hospitalisations in at-risk children: A systematic review.

AIM: To identify interventions that reduce hospitalisations and improve related outcomes in children at risk of asthma hospital admissions. METHODS: Medline, Embase, Pubmed and Cochrane Library search from January 2002 to April 2020. INCLUSION CRITERIA: randomised controlled trials of any intervention for children with asthma who are at risk of hospitalisations. OUTCOMES: hospitalisation (primary outcome), rescue oral corticosteroid use, school absences, quality of life and cost-effectiveness. RESULTS: Twelve randomised controlled trials were conducted with 2719 participants. Due to heterogeneity of interventions and reporting of outcomes, a meta-analysis was not conducted. Multi-modal interventions comprising caregiver education, reduction of home environmental allergens and regular follow-up reduced hospitalisations, rescue corticosteroid use and improved quality of life. Cost-effectiveness was not reported. Three studies scored an overall low risk of bias, and nine had some concerns. CONCLUSION: Multi-modal interventions can be effective in reducing hospitalisations, rescue oral corticosteroid use and quality of life but cost-effectiveness is unknown.

Magnetically Modulated Fluorescence of Nitrogen-Vacancy Centers in Nanodiamonds for Ultrasensitive Biomedical Analysis.

The negatively charged nitrogen-vacancy center in fluorescent nanodiamonds (FNDs) is a point defect with unique magneto-optical properties. It emits far-red fluorescence at ∼700 nm, and its intensity can be magnetically modulated with a depth of more than 10% at a field strength of 30 mT. We have closely examined this property and illustrated its practical use in biomedicine by applying a periodic, time-varying magnetic field to FNDs deposited on a surface or dispersed in a solution with a lock-in detection method. We achieved selective and sensitive detection of 100 nm FNDs on a nitrocellulose membrane at a particle density of 0.04 ng/mm2 (or ∼2 × 104 particles/mm2) and in an aqueous solution with a particle concentration of 1 ng/mL (or ∼1 fM) in 10 s as the detection limits. The utility and versatility of the technique were demonstrated with an application to background-free detection of FNDs as reporters for FND-based lateral flow immunoassays as well as selective quantification of FNDs in tissue digests for in vivo studies.

Arterial Structure and Function Following Viral Myocarditis.

Acute viral myocarditis is an uncommon inflammatory disease of the myocardium. Little is known about the long-term cardiovascular risk for individuals who have recovered from the acute illness. We compared intermediate vascular phenotypes relating to arterial structure (aortic and carotid intima-media thickness) and function (pulse wave velocity, carotid arterial distensibility and compliance) in 15 participants, a median of 9.1 years after an episode of acute viral myocarditis, and 45 control participants. Following adjustment for age, sex and triglycerides, there were no differences in mean and maximum carotid and aortic intima-media thickness, pulse wave velocity, carotid artery distensibility and compliance between viral myocarditis participants and controls. In conclusion, we found no evidence of changes in intermediate vascular phenotypes indicative of increased cardiovascular risk in individuals who had fully recovered from viral myocarditis.

Innate immune responses following Kawasaki disease and toxic shock syndrome.

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1ß production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory.

Macro- and Microvascular Parameters After Toxic Shock Syndrome.

Whether individuals who had toxic shock syndrome in childhood have differences in macro- and retinal microvascular parameters indicative of increased cardiovascular risk is unknown. We found no evidence of adverse macrovascular changes in 22 toxic shock syndrome participants compared with 60 control participants. Microvascular comparisons showed a reduction in retinal total fractal dimension, which has been associated with cardiovascular risk factors in children.

Evidence of Microvascular Changes in the Retina following Kawasaki Disease.

It is unclear whether all children with Kawasaki disease (KD) have increased later cardiovascular risk. The retinal microvasculature reflects changes in the microcirculation and is associated with traditional cardiovascular risk factors and events. The aim of this study was to investigate retinal microvascular parameters in two populations of patients with previous KD and control participants. We performed case-control studies of 116 (57 patients and 59 control participants) Australian and 156 (78 patients and 78 control participants) Singaporean individuals, at least two years since their acute illness. Standardised retinal photographs were graded by trained technicians using a semi-automated software, which quantifies the retinal microvasculature (calibre, branching angle, fractal dimensions, and tortuosity). Retinal venules of Singaporean KD patients were 9.67 µm (95% CI 4.87 to 14.51, p < 0.001) larger than control participants following correction for traditional cardiovascular risk factors. An incremental increase in the size of retinal venules in those with coronary artery abnormalities was observed. There was limited evidence that retinal venules were larger in Australian KD patients with coronary artery abnormalities compared to control participants (7.34 µm, 95% CI 1.30 to 15.99, p = 0.10). Differences in retinal microvasculature were particularly evident in Singaporean KD patients. Larger retinal venules may reflect chronic inflammation and endothelial dysfunction, and are associated with coronary artery disease in adults.

Toxic shock syndrome in Australian children.

BACKGROUND: There are limited data describing the epidemiology, management and outcomes of children with toxic shock syndrome (TSS), a potentially life-threatening illness. Here, we describe the incidence, clinical features, treatment and outcome of children with staphylococcal and streptococcal TSS in Victoria, Australia. METHODS: Retrospective chart review of children admitted between 2003 and 2014 to two tertiary paediatric referral centres who fulfilled the Centers for Disease Control and Prevention case definition of TSS. RESULTS: There were 62 cases over the 11-year period; 43 staphylococcal TSS and 19 streptococcal TSS. The majority (46 (74%)) of cases were admitted to an intensive care unit and 44 (71%) required inotropic support. Compared with those with staphylococcal TSS, patients with streptococcal TSS were younger, more unwell and more likely to have residual morbidity. Adjunctive therapy with intravenous immunoglobulin or clindamycin was used in 58 (94%) of cases and fresh frozen plasma was used in 15 (24%). Seven patients received extracorporeal membrane oxygenation. All patients survived. CONCLUSIONS: This study highlights the importance of early recognition of TSS and supports rapid tertiary referral and intensive care management, which includes the use of adjunctive therapy with intravenous immunoglobulin and clindamycin.

Kawasaki disease and cardiovascular risk: a comprehensive review of subclinical vascular changes in the longer term.

UNLABELLED: Studies of subclinical vascular changes post-Kawasaki disease indicate that, in general, individuals with a history of coronary artery aneurysms have increased carotid intima-media thickness, evidence of endothelial dysfunction, and increased arterial stiffness, possibly indicative of heightened cardiovascular risk. The results are less consistent for low-risk groups. CONCLUSION: Until data are available from larger prospective studies, it is prudent to advise families of individuals with a history of Kawasaki disease to minimise traditional modifiable cardiovascular risk factors.