Pandemic Incident Management for Vaccine Safety Challenges: Victoria's Alert Advisory Group Experience.

Safe vaccines are critical for biosecurity protection, yet adverse events-rightly or wrongly attributed to immunization-potentially cause rapid loss of confidence, reduced vaccine uptake, and resurgence of preventable disease. Effective vaccine safety incident management is essential to provide assessment and lead appropriate actions to ensure vaccination programs are safe and mitigate unwarranted crisis escalation that could damage vaccine programs and the effective control of vaccine preventable disease outbreaks or pandemics. Incident management systems (IMS) are used globally to direct emergency management response, particularly for natural disasters of fire, flood, and storm. Public health is equally an emergency response and can therefore benefit from these command control constructs. While examples of IMS for outbreak response and mass immunization logistics exist, there is little to no information on their use in vaccine safety. We describe Australia's vaccine safety Alert Advisory Group establishment in Victoria during the COVID-19 pandemic and onward embedding into routine practice, anticipant of new vaccines, and the next biosecurity threat.

Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) offers patients with stage I non-small-cell lung cancer (NSCLC) a safe, effective radical therapy option. The impact of introducing SABR at a Scottish regional cancer centre was studied. METHODS: The Edinburgh Cancer Centre Lung Cancer Database was assessed. Treatment patterns and outcomes were compared across treatment groups (no radical therapy (NRT), conventional radical radiotherapy (CRRT), SABR and surgery) and across three time periods reflecting the availability of SABR (A, January 2012/2013 (pre-SABR); B, 2014/2016 (introduction of SABR); C, 2017/2019, (SABR established)). RESULTS: 1143 patients with stage I NSCLC were identified. Treatment was NRT in 361 (32%), CRRT in 182 (16%), SABR in 132 (12%) and surgery in 468 (41%) patients. Age, performance status, and comorbidities correlated with treatment choice. The median survival increased from 32.5 months in time period A to 38.8 months in period B to 48.8 months in time period C. The greatest improvement in survival was seen in patients treated with surgery between time periods A and C (HR 0.69 (95% CI 0.56-0.86), p < 0.001). The proportion of patients receiving a radical therapy rose between time periods A and C in younger (age ≤ 65, 65-74 and 75-84 years), fitter (PS 0 and 1), and less comorbid patients (CCI 0 and 1-2), but fell in other patient groups. CONCLUSIONS: The introduction and establishment of SABR for stage I NSCLC has improved survival outcomes in Southeast Scotland. Increasing SABR utilisation appears to have enhanced the selection of surgical patients and increased the proportion of patients receiving a radical therapy.

Vaccine safety in Australia during the COVID-19 pandemic: Lessons learned on the frontline.

Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC), Victoria's vaccine safety service for reporting adverse events following immunisation (AEFI), has provided integrated spontaneous surveillance and clinical services for individuals affected by AEFI since 2007. We describe SAEFVIC's response to the COVID-19 vaccine program, and reflect on lessons learned for vaccine safety. The massive scale of the Australian COVID-19 vaccine program required rapid adaptations across all aspects of SAEFVIC's vaccine safety services. Collection of AEFI reports was streamlined and expanded, incorporating both spontaneous and active surveillance data. Dramatically increased report volumes were managed with additional staffing, and innovations to automate, filter, and triage reports for priority follow up. There were two major adverse events of special interest (AESI): thrombosis with thrombocytopaenia syndrome and myocarditis, with multiple other AESI also investigated. Rapid escalation mechanisms to respond to AESI were established, along with AESI-specific databases for enhanced monitoring. Vaccine education and training resources were developed and public-facing vaccine safety reports updated weekly. Frequent communication with local and national government and regulatory bodies, and consultation with specialist groups was essential. The COVID-19 vaccine program has highlighted the importance of vaccine safety in supporting public confidence in vaccines and informing evidence-based immunisation policy. Supporting the COVID-19 vaccine program has required flexibility in adapting to policy changes and evolving vaccine safety signals, careful triage and prioritisation, informatics innovation, and enhanced engagement with the public regarding vaccine safety. Long-term investment to continue strengthening vaccine safety systems, building on lessons learned, will be essential for the ongoing success of Australian vaccination programs.

Status epilepticus following vaccination in children aged ≤24 months: A five-year retrospective observational study.

BACKGROUND: Status epilepticus is associated with significant morbidity and mortality. While vaccine-proximate status epilepticus (VP-SE) has rarely been associated with cases of Dravet syndrome, it is not known whether VP-SE differs clinically from non-vaccine proximate status epilepticus (NVP-SE). METHODS: Medical records of children aged ≤24 months, presenting to one of five Australian tertiary pediatric hospitals with their first episode of status epilepticus from 2013 to 2017 were identified using ICD-coded discharge diagnoses. Vaccination history was obtained from the Australian Immunisation Register. Hospitalization details, subsequent epilepsy diagnosis, and vaccination uptake were compared between VP-SE and NVP-SE cases. RESULTS: Of 245 first status epilepticus hospitalization with immunization records, 35 (14%) were VP-SE and 21 (60%) followed measles-containing vaccines. Vaccine-proximate status epilepticus cases had a median age of 12.5 months [IQR 7.1-14.73], 23 (66%) were in males, 15 (43%) were febrile status epilepticus and 17 (49%) had an infection confirmed. There were no significant differences in hospitalization duration (P = 0.50) or intensive care unit admission (P = 0.42) between children with VP-SE compared to children with NVP-SE. Children with no history of seizures at their first VP-SE had longer hospitalizations, were more likely to require intensive care unit admission, but were less likely to have a subsequent diagnosis of epilepsy than children with previous seizures at their first VP-SE. CONCLUSION: First VP-SE was predominantly associated with a measles-containing vaccine at 12-months of age. Seizure severity was no different between first VP-SE and first NVP-SE. In children with VP-SE, subsequent seizure admissions and epilepsy diagnosis were associated with having seizure prior to their first SE.

Revaccination outcomes of children with vaccine proximate seizures.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

SAEFVIC: Surveillance of adverse events following immunisation (AEFI) in Victoria, Australia, 2018.

BACKGROUND: SAEFVIC is the Victorian surveillance system for adverse events following immunisation (AEFI). It enhances passive surveillance by also providing clinical support and education to vaccinees and immunisation providers. This report summarises surveillance, clinical and vaccine pharmacovigilance activities of SAEFVIC in 2018. METHODS: A retrospective observational cohort study of AEFI reports received by SAEFVIC in 2018, compared with previous years since 2008. Data were categorised by vaccinee demographics of age, sex, pregnancy and Indigenous status, vaccines administered and AEFI reactions reported. Age cohorts were defined as infant (0-12 months); young child (1-4 years); school-aged (5-17 years); adult (18-64 years); and older person (65+ years). Proportional reporting ratios were calculated for signal investigation of serious adverse neurological events with all vaccines and with influenza vaccines. Clinical support services and educational activities are described. RESULTS: SAEFVIC received 1730 AEFI reports (26.8 per 100,000 population), with 9.3% considered serious. Nineteen percent (n = 329) attended clinical review. Annual AEFI reporting trends increased for infants, children and older persons, but were stable for school-aged and adult cohorts. Females comprised 55% of all reports and over 80% of reports among adults. There were 17 reports of AEFI in pregnant women and 12 (0.7%) in persons identifying as Indigenous Australians. A possible signal regarding serious adverse neurological events (SANE) was detected, but was not supported by signal validation testing. A clinical investigation is ongoing. Two deaths were reported coincident to immunisation with no evidence of causal association. CONCLUSION: SAEFVIC continues to provide robust AEFI surveillance supporting vaccine safety monitoring in Victoria and Australia, with new signal detection and validation methodologies strengthening capabilities.

PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens.

BACKGROUND: Over 1 million men are diagnosed with prostate cancer each year worldwide, with a wide range of research programs requiring access to patient tissue samples for development of improved diagnoses and treatments. A random sampling of prostate tissue is sufficient for certain research studies; however, there is growing research need to target areas of the aggressive tumor as fresh tissue. Here we set out to develop a new pathway "PEOPLE: PatiEnt prOstate samPLes for rEsearch" to collect high-quality fresh tissue for research use, using magnetic resonance imaging (MRI) to target areas of tumor and benign tissue. METHODS: Prostate tissue was sampled following robotic radical prostatectomy, using MRI data to target areas of benign and tumor tissue. Initially, 25 cases were sampled using MRI information from clinical notes. A further 59 cases were sampled using an optimized method that included specific MRI measurements of tumor location along with additional exclusion criteria. All cases were reviewed in batches with detailed clinical and histopathological data recorded. For one subset of samples, DNA was extracted and underwent quality control. Ex vivo culture was carried out using the gelatin sponge method for an additional subset. RESULTS: Tumor was successfully fully or partially targeted in 64% of the initial cohort and 70% of the optimized cohort. DNA of high quality and concentration was isolated from 39 tumor samples, and ex vivo culture was successfully carried out in three cases with tissue morphology, proliferation, and apoptosis remaining comparable before and after 72 hours culture. CONCLUSION: Here we report initial data from the PEOPLE pathway; using a method for targeting areas of tumor within prostate samples using MRI. This method operates alongside the standard clinical pathway and minimizes additional input from surgical, radiological, and pathological teams, while preserving surgical margins and diagnostic tissue.

Consumer reporting of adverse events following immunization.

Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P<0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P=0.018) and 10% more likely to result in specialist clinic attendance (P<0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity.