Live vaccines following intravenous immunoglobulin for Kawasaki disease: Are we vaccinating appropriately?

AIM: Australian and New Zealand guidelines recommend that live vaccines be postponed for 11 months after treatment of Kawasaki disease (KD) with intravenous immunoglobulin (IVIG). We aimed to describe patterns of live-vaccine administration after KD treatment, focusing on the measles-mumps-rubella/measles-mumps-rubella-varicella (MMR/MMRV) vaccines, and to compare real-world practice with current recommendations. METHODS: We combined data from inpatient Electronic Health Records and the Australian Immunisation Register for all children who received IVIG for the treatment of KD under the age of 5 years at two Australian tertiary children's hospitals over a 12-year period. Children who received IVIG <11 months before a scheduled MMR/MMRV were deemed 'at risk' of breaching the guidelines, and those whose subsequent vaccination occurred <11 months after the IVIG were deemed to have 'breached' the guidelines. RESULTS: Of those at risk, three-quarters (76%) breached the guidelines for their first MMR/MMRV. Findings were similar (50%-80%) for the second MMR/MMRV dose. CONCLUSIONS: The majority of Australian children treated for KD with IVIG may not be optimally protected by MMRV vaccination. Immunisation systems should address this avoidable risk.

Clinical use conditions of lead deployment and simulated lead fracture rate in left bundle branch area pacing.

INTRODUCTION: Left bundle branch area pacing (LBBAP) is achieved by advancing the lead tip deep in the septum. Most LBBAP implants are performed using the Medtronic SelectSecure™ MRI SecureScan™ Model 3830 featuring a unique 4 Fr fixed helix lumenless design. Details of lead use conditions and long-term reliability have not been reported. This study was designed to quantify the mechanical use conditions for the 3830 lead during and after LBBAP implant, and to evaluate reliability using bench testing and simulation. METHODS: Fifty bradycardia patients with implantation of the 3830 lead for LBBAP were enrolled. Use conditions of lead deployment at implantation were collected and computed tomography (CT) scans were performed at 3-month follow-up. Curvature amplitude along the pacing lead was determined with CT images. Fatigue bending was performed using accelerated testing in a more severe environment than routine clinical use conditions. Conductor fracture rate in a simulated patient population was estimated based on clinical use conditions and fatigue test results. RESULTS: The number of attempts to place the 3830 lead for LBBAP was 2.1 ± 1.3 (range: 1-7) with 13 ± 6 lead rotations at the final attempt. Extreme implant conditions were simulated in bench testing with 5 applications of 20 turns followed by up to 400 million bending cycles. Reliability modeling predicted a 10-year fracture rate of 0.02%. CONCLUSIONS: LBBAP implants require more lead rotations than standard pacing implants and result in unique lead bending. Application of simulated LBBAP use conditions to the 3830 lead in an accelerated in-vitro model does not produce excess conductor fractures. IMAGE-LBBP Study ID of ClinicalTrial.GOV: NCT04119323.

Epidemiology of Kawasaki disease in Australia using two nationally complete datasets.

AIM: The incidence of Kawasaki disease (KD) is reported to be increasing in some populations. We sought to describe long-term trends in the incidence and epidemiology of KD in Australia over 25 years. METHODS: Two nationally complete administrative datasets relevant to KD in Australia were analysed and compared. The Australian Red Cross Lifeblood Supply Tracking Analysis Reporting System (STARS) recorded all doses of immunoglobulin (IVIG) approved in Australia between January 2007 and June 2016. The Australian Institute of Health and Welfare National Hospital Morbidity Database (NHMD) records all episodes of care in hospitals across Australia. Data relevant to KD were extracted an analysed, with comparisons made for the period of data overlap. RESULTS: During the period of data overlap (2007-2015) the IVIG treatment rate in the 0- to 4-year age group (calculated from STARS) was 14.31 per 100 000 person-years (95% confidence interval 13.67-14.97). The hospitalisation rate in the same age group (calculated from the NHMD) was 14.99 per 100 000 person-years (95% confidence interval 14.33-15.66). Hospitalisation rates rose at an average rate of 3.54% annually over the 25 years to 2017 in the 0- to 4-year age group, almost exclusively in the 1- to 4-year age group. CONCLUSIONS: There is evidence of increasing KD diagnosis in Australia. Similar trends have also been reported in Asia but not in North America or Europe. Increasing diagnosis may reflect a true increase in disease incidence, increasing recognition or overdiagnosis. Further research is needed to determine the cause for these trends.

Prospective characterisation of SARS-CoV-2 infections among children presenting to tertiary paediatric hospitals across Australia in 2020: a national cohort study.

OBJECTIVE: To present Australia-wide data on paediatric COVID-19 and multisystem inflammatory syndromes to inform health service provision and vaccination prioritisation. DESIGN: Prospective, multicentre cohort study. SETTING: Eight tertiary paediatric hospitals across six Australian states and territories in an established research surveillance network-Paediatric Active Enhanced Disease (PAEDS). PARTICIPANTS: All children aged <19 years with SARS-CoV-2 infection including COVID-19, Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) and Kawasaki-like disease TS infection (KD-TS) treated at a PAEDS site from 24 March 2020 to 31 December 2020. INTERVENTION: Laboratory-confirmed SARS-CoV-2 infection. MAIN OUTCOME: Incidence of severe disease among children with COVID-19, PIMS-TS and KD-TS. We also compared KD epidemiology before and during the COVID-19 pandemic. RESULTS: Among 386 children with SARS-CoV-2 infection, 381 (98.7%) had COVID-19 (median 6.3 years (IQR 2.1-12.8),53.3% male) and 5 (1.3%) had multisystem inflammatory syndromes (PIMS-TS, n=4; KD-TS, n=1) (median 7.9 years (IQR 7.8-9.8)). Most children with COVID-19 (n=278; 73%) were Australian-born from jurisdictions with highest community transmission. Comorbidities were present in 72 (18.9%); cardiac and respiratory comorbidities were most common (n=32/72;44%). 37 (9.7%) children with COVID-19 were hospitalised, and two (0.5%) required intensive care. Postinfective inflammatory syndromes (PIMS-TS/KD-TS) were uncommon (n=5; 1.3%), all were hospitalised and three (3/5; 60%) required intensive care management. All children recovered and there were no deaths. KD incidence remained stable during the pandemic compared with prepandemic. CONCLUSIONS: Most children with COVID-19 had mild disease. Severe disease was less frequent than reported in high prevalence settings. Preventative strategies, such as vaccination, including children and adolescents, could reduce both the acute and postinfective manifestations of the disease.

Paediatric Active Enhanced Disease Surveillance (PAEDS) 2019: Prospective hospital-based surveillance for serious paediatric conditions.

INTRODUCTION: The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is an Australian hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine preventable diseases and potential adverse events following immunisation (AEFI). This report presents surveillance data for 2019. METHODS: Specialist nurses screened hospital admissions, emergency department records, laboratory and other data on a daily basis in seven paediatric tertiary referral hospitals across Australia, to identify children with the conditions under surveillance. Standardised protocols and case definitions were used across all sites. In 2019, the conditions under surveillance comprised: acute flaccid paralysis (AFP; a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal and invasive Group A streptococcus diseases and two new conditions, Kawasaki disease and gram-negative bloodstream infections. An additional social research component continued to evaluate parental attitudes to influenza vaccination. RESULTS: PAEDS captured 2,701 cases for 2019 across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach the World Health Organization reporting targets for detection of poliomyelitis cases; demonstration of high influenza activity in 2019 and influenza-associated deaths in ACE cases; identification of key barriers to influenza vaccination of children hospitalised for acute respiratory illness; reporting of all IS cases associated with vaccine receipt to relevant state health department; and showing a further reduction nationally in varicella cases. Enhanced pertussis surveillance continued to capture controls to support vaccine efficacy estimation. Invasive meningococcal disease surveillance showed predominance of serotype B and a reduction in cases nationally. Surveillance for invasive group A streptococcus captured severe cases in children. Monitoring of Kawasaki disease incidence and gram-negative bloodstream infections commenced. CONCLUSIONS: PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using sentinel hospital-based enhanced surveillance. Keywords: paediatric, surveillance, child, hospital, vaccine preventable diseases, adverse event following immunisation, acute flaccid paralysis, encephalitis, influenza, intussusception, pertussis, varicella zoster virus, meningococcal, group A streptococcus, Kawasaki, bloodstream infections.

Variation in the management of Kawasaki disease in Australia and New Zealand: A survey of paediatricians.

AIM: This study aimed to describe the current management practices for Kawasaki disease (KD) in Australia and New Zealand. METHODS: We performed a secondary analysis on the Australian and New Zealand responses to a large international survey of clinicians' perspectives on KD diagnosis and management. RESULTS: There was general consensus among Australian and New Zealand clinicians regarding the indications for intravenous immunoglobulin and aspirin in the management of acute KD. There was less consensus on the dose of these agents, the definition and management of treatment-resistant KD and the approach to long-term thromboprophylaxis. CONCLUSION: Most clinicians use intravenous immunoglobulin for primary treatment of KD. There is variation regarding other aspects of KD diagnosis and important management issues. Future studies should confirm whether this reported variation occurs in real-world practice and assess potential impacts on patient outcome.

Update on the COVID-19-associated inflammatory syndrome in children and adolescents; paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2.

We provide an update on the state of play with regards a newly described inflammatory condition which has arisen during the current SARS-CoV-2 pandemic. The condition has been named paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 or multisystem inflammatory syndrome in children. This condition has shown significant similarities to Kawasaki disease and toxic shock syndrome.

Density Functional Theory Study of the Gas Phase and Surface Reaction Kinetics for the MOVPE Growth of GaAs1-yBiy.

The kinetics of chemical reactions occurring during the metal-organic vapor phase epitaxy (MOVPE) of GaAs1-yBiy have been studied using density functional theory (DFT). GaAs1-yBiy is a metastable semiconductor alloy that has potential applications in high-performance long-wavelength emitters. Its growth is complicated by the low solubility of Bi within the GaAs lattice, which leads to phase segregation under conventional III-V semiconductor growth conditions. In this study, the thermochemical and kinetic parameters of the gas-phase pyrolysis and surface reactions occurring in the MOVPE growth of GaAs1-yBiy from trimethyl bismuth, tertiary butyl arsine, and triethyl gallium are calculated from first-principles electronic structure and vibrational mode calculations. These calculations indicate that the pyrolysis products AsH2 and Bi(CH3)2 are the principle sources for the deposition of their respective metallic elements. The surface-adsorbed methyl species and their interaction with the gas-phase pyrolysis products lead to the self-limiting growth described within this model. The calculated thermochemical and kinetic values provide initial parameters for the development of a microkinetic model of GaAs1-yBiy deposition.

Hands-Only Cardiopulmonary Resuscitation Education: A Comparison of On-Screen With Compression Feedback, Classroom, and Video Education.

STUDY OBJECTIVE: We compare 3 methods of hands-only cardiopulmonary resuscitation (CPR) education, using performance scores. A paucity of research exists on the comparative effectiveness of different types of hands-only CPR education. This study also includes a novel kiosk approach that has not previously been studied, to our knowledge. METHODS: A randomized, controlled study compared participant scores on 4 hands-only CPR outcome measures after education with a 25- to 45-minute practice-while-watching classroom session (classroom), 4-minute on-screen feedback and practice session (kiosk), and 1-minute video viewing (video only). Participants took a 30-second compression test after initial training and again after 3 months. RESULTS: After the initial education session, the video-only group had a lower total score (compressions correct on hand placement, rate, and depth) (-9.7; 95% confidence interval [CI] -16.5 to -3.0) than the classroom group. There were no significant differences on total score between classroom and kiosk participants. Additional outcome scores help explain which components negatively affect total score for each education method. The video-only group had lower compression depth scores (-9.9; 95% CI -14.0 to -5.7) than the classroom group. The kiosk group outperformed the classroom group on hand position score (4.9; 95% CI 1.3 to 8.6) but scored lower on compression depth score (-5.6; 95% CI -9.5 to -1.8). The change in 4 outcome variables was not significantly different across education type at 3-month follow-up. CONCLUSION: Participants exposed to the kiosk session and those exposed to classroom education performed hands-only CPR similarly, and both groups showed skill performance superior to that of participants watching only a video. With regular retraining to prevent skills decay, the efficient and free hands-only CPR training kiosk has the potential to increase bystander intervention and improve survival from out-of-hospital cardiac arrest.

Bio-production of gaseous alkenes: ethylene, isoprene, isobutene.

To reduce emissions from petrochemical refinement, bio-production has been heralded as a way to create economically valuable compounds with fewer harmful effects. For example, gaseous alkenes are precursor molecules that can be polymerized into a variety of industrially significant compounds and have biological production pathways. Production levels, however, remain low, thus enhancing bio-production of gaseous petrochemicals for chemical precursors is critical. This review covers the metabolic pathways and production levels of the gaseous alkenes ethylene, isoprene, and isobutene. Techniques needed to drive production to higher levels are also discussed.

Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects.

Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell), prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented that characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression was not affected by ethanol exposure, but E-cadherin distribution, which controls epiboly and gastrulation, was changed. E-cadherin was redistributed into cytoplasmic aggregates in blastomeres and dramatically redistributed in the extraembryonic yolk cell. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a), which controls epiboly, was significantly reduced in ethanol exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue) microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.