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The rate of anaphylaxis following COVID-19 vaccinations is estimated to be 2–11 cases per million doses administered. However, adrenaline is occasionally used in individuals who are later diagnosed with immunisation stress-related responses, as their initial presenting signs and symptoms can appear similar to that of anaphylaxis. This study aims to describe the clinical profile of individuals who had received adrenaline following a COVID-19 vaccine and their subsequent revaccination outcomes. We examined notifications of cases who had received adrenaline following a COVID-19 vaccine in New South Wales, Australia. The cases were classified into Brighton Collaboration Case Definition (BCCD) for anaphylaxis, their clinical presentation, management and subsequent revaccination outcomes were compared. From 22 February 2021 to 30 September 2021, there were 222 cases where adrenaline was administered. Of these, 32 (14 %) fulfilled Level 1 BCCD, 59 (27%) Level 2, 2 (1%) Level 3, 97 (44%) Level 4 and 32 (14 %) Level 5. The most commonly reported symptoms were sensation of throat closure (n = 116, 52%), difficulty breathing (n = 82, 37%) and nausea (n = 55, 25 %). Of the 176 (79%) individuals who proceeded to further vaccination, 89 (51%) received the same vaccine formulation and only 14 (8%) experienced another allergic adverse event with 9 (5%) receiving adrenaline. Less than one in five individuals who received adrenaline met Level 1 BCCD criteria for anaphylaxis. Many reactions that were treated with adrenaline had little to no diagnostic certainty of anaphylaxis and in such cases repeat vaccination had a high likelihood of being tolerated. Increased awareness and education on objective signs and symptoms of anaphylaxis is required to ensure appropriate use of adrenaline. [ABSTRACT FROM AUTHOR]

Seizures, whether febrile or afebrile, occurring within 14 days following vaccination can be considered as vaccine proximate seizures (VPSs). While the attributable risk and clinical severity of first febrile VPS is well known, the risk and clinical outcomes of VPS recurrence is less well defined. We conducted a retrospective review of revaccination management and outcomes in children who experienced a VPS as their first seizure seen in Australian Specialist Immunisation Clinics between 2013 and 2017. Vaccination outcomes were compared between children who had a VPS as their only seizure (VPS only) and children who had further non-vaccine proximate seizures following their initial VPS (VPS+) prior to review at the clinic. We identified 119 children with a VPS as their first seizure, of which 61 (51%) went on to have other seizures (VPS+). Children with VPS+ were more likely to present at a younger age (6.2 vs 12.5 months, P = 0.03), with afebrile seizures (42.6% vs 15.5%, P = 0.002) compared to VPS only children. VPS recurrence on revaccination was uncommon in both groups, but more common in VPS+ children (12.5% vs 2.4%, P = 0.07). Having an epilepsy diagnosis, specifically Dravet syndrome, was associated with VPS recurrence (P < 0.001). Of the four children with Dravet syndrome who had VPS recurrence, all had status epilepticus following revaccination. In children who presented with a single VPS as their only seizure, VPS recurrence on revaccination was uncommon. Children who had multiple non-vaccine proximate seizures following their initial VPS (VPS+) were more likely to present with afebrile VPS, at a younger age and have a VPS recurrence with vaccination. In these children, particularly those aged < 12 months, assessment and investigation for diagnosis of Dravet syndrome should be considered and additional precautions for revaccination undertaken as they are at highest risk of VPS recurrence. [ABSTRACT FROM AUTHOR]

Purpose: SCN1A variants cause a spectrum of epilepsy syndromes from Dravet Syndrome, a severe epileptic encephalopathy of early infancy to the milder disorder of genetic epilepsy with febrile seizures plus (GEFS+). These genetic epilepsies are associated with increased risk of poor outcome including complications of status epilepticus and early mortality. Individualised management of young children known to be at increased risk should be considered, such as around vaccination management.Methods: We describe two siblings with a novel pathogenic SCN1A variant, their management and clinical outcomes following routine childhood vaccinations.Results: The index case who had a family history of epilepsy of unknown genetic aetiology, died from hypoxic ischemic encephalopathy following his 12-month vaccinations, in the context of status epilepticus and enterovirus 71 infection. The sibling of the index case with the same SCN1A variant was subsequently managed with prophylactic regular sodium valproate and additional clobazam post vaccination to reduce the risk of seizure. She has successfully completed the childhood immunisations to 18 months with no seizures and normal neurodevelopmental progress.Conclusion: As the aetiology of genetic epilepsies is increasingly known in early childhood, opportunities to personalise care, minimise risks and optimise outcomes are changing. Further research is needed on the risks and benefits of symptomatic and preventative management of seizures around vaccinations in young children with genetic epilepsies. [ABSTRACT FROM AUTHOR]

• Background rates help contextualise potential COVID-19 vaccine safety signals. • Large linked data bases for calculating background rates provide reliable estimates. • Most Australian background rates aligned with international estimates. • Background rates of myocarditis were highest in males aged 18–24 years. • Rates may vary due to coding systems and practices; local estimates are optimal. Determining background rates of medical conditions identified as adverse events of special interest (AESI) that may occur following COVID-19 vaccination is important for contextualising and investigating potential vaccine safety signals. We conducted a retrospective population-based cohort study using linked emergency department, hospitalisation and death data for 2017 and 2018 from Australia's most populous state, New South Wales. Incident cases of select neurological conditions, arterial or venous thromboembolic conditions, secondary thrombocytopenia, myocarditis/pericarditis, and unique events of anaphylaxis and generalised convulsions were identified using internationally agreed upon diagnostic (ICD-10) codes. State-specific rates per 100,000 person-years were calculated, with further stratification by age group and sex where clinically relevant to the condition, and the number of expected cases nationally in one and 6 weeks was estimated. Background rates of selected neurological conditions were low with the exception of generalised convulsions for which 1,599–1,872 cases were estimated nationally in a 1-week period in the absence of vaccination. Using a narrow case definition, rates of Guillain-Barré Syndrome (3.9 per 100,000 person-years) were higher than international rates reported elsewhere. Thromboembolic and cerebral venous sinus thrombosis event rates increased with age. Myocarditis occurred more commonly in males, and was highest in males aged 18–24 years, with an estimated 1–4 cases expected nationally in a 1-week period. Using routinely collected linked healthcare data provides localised estimates of background rates of new onset or periodic AESI which enables rapid estimation of observed-versus-expected rates of events reported following COVID-19 vaccination. This Australian-specific analysis contributes AESI background rates which can be compared with those from other countries to enhance understanding of geographic variability in the frequency of specific AESI in the absence of vaccination, and can be utilised for signal detection during program implementation. [ABSTRACT FROM AUTHOR]

Objectives: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.Study Design: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study.Results: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%).Conclusions: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] We altered the average pore diameters of TiO2 mesoporous thin films using TiCl4 post-treatments. [•] The ion diffusivities corresponding to variable pore diameters were measured using DC polarization measurements. [•] Two opposite diffusion behaviors were present under the same scheme with a sharp transition in between. [•] Surface diffusion is found to be involved in the mass transfer process. [ABSTRACT FROM AUTHOR]