Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.

BACKGROUND: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. METHODS AND FINDINGS: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. CONCLUSIONS: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735084 and NCT01174849.

Positive impacts of a dedicated General Paediatrics "home" ward in a tertiary paediatric Australian hospital.

AIMS: Whilst a centralised model of care intuitively makes sense and is advocated in other subspecialty areas of medicine, there is a paucity of supportive evidence for General Paediatrics. Following ward restructuring at our tertiary paediatric centre in preparation for the COVID-19 pandemic, a new dedicated General Paediatrics ward was established. We evaluated medical and nursing staff well-being, morale and perceived impacts on care after the ward's establishment. METHODS: Experiences were sought from medical and nursing staff whom had worked across both previous wards caring for General Paediatrics patients, as well as the new dedicated General Paediatrics ward. Mandated responses used the format of much better, better, same, worse and much worse. RESULTS: A total of 73/82 (89%) medical and nursing staff completed the survey. A greater than 90% improved or neutral response was noted for 31/35 (89%) questions. About 80% of staff reported the new dedicated General Paediatrics ward provided a better or much better team-based approach, time efficient approach and overall model of care. A much better or better response was reported for communication between medical and nursing staff in 68%, team comradery in 69%, supportive/helpful nursing staff in 74%, job stress level in 66% and staff morale in 60% of respondents. CONCLUSIONS: Overwhelmingly positive responses from this study support a centralised or "home" ward model of care for General Paediatrics patients in a tertiary paediatric setting. Our findings may be relevant to General Paediatrics teams in other centres currently using multiple wards to manage their patients.

Embedding clinical audit into everyday practice: Essential methodology for all clinicians.

Clinical audits should underpin everything we do as clinicians - to constantly evaluate and improve our day-to-day clinical practice. Errors in practice, suboptimal practice or inefficiencies can occur in any part of our health-care system, despite the training and best intentions of health-care professionals. Audits examine how clinical care is being provided and whether benchmarks are being met, and identify opportunities for improvement. Detection of problems is greatly improved when audits of practice are undertaken, ideally regularly, and as part of a continuous process of quality improvement. Audits also make ideal entry-level research projects for students and trainees through to senior clinicians. Despite a willingness to undertake audits, and improvements in both undergraduate and postgraduate training, not all clinicians have had formal teaching in audit methodology, and a refresher can also be helpful. This short overview covers basic clinical audit methods, discusses key facilitators for embedding audit into every day practice, and references additional resources to guide clinicians wanting to take up the challenge of regularly and efficiently undertaking audits.

Can Research Training be Improved in Health Professional Student Curricula? A Qualitative Descriptive Study of Health Students' Experiences with an Integrated Research Training Platform.

Introduction: Project-based learning is currently the status quo for research training for health professional students; however, it alone is not sufficient for holistic development of research skills. One promising style of intervention that can complement project-based research training is a centralised hub of e-learning resources. Therefore, we explored the perception of health professionals in tertiary education, towards the E-learning hub named 'Health and Medical Sciences Research Modules'. Specifically, we explored (1) the role the Modules can play in supporting students in their research training courses, (2) the perception of the selection of topics and content quality and (3) student engagement with content. Methods: Semi-structured interviews were conducted via the online platform Zoom for University of Western Australia 3rd- and 4th-year Dental doctoral students, and 2nd-year Master of Pharmacy students. Interview transcripts were analysed using the framework method, to identify manifest and latent level themes. Results: Eleven participants completed the interview, including five dentistry and six pharmacy students. The analysis yielded numerous manifest level themes including selection and depth of topics, and four latent level themes: content volume and balance, relevance of content to project, alignment and sequencing, and interactivity. Discussion: The present study suggests the Modules content and the online platform were well received as a complementary intervention to project-based learning. However, issues such as content oversaturation emerged as topics which can be addressed to improve the learning experience. These topics should be considered when considering further implementation of e-learning hubs to complement project-based learning, across Australia and worldwide.

Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials.

BACKGROUND: Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules. METHODS: PREVIX_BOOST was a parallel, open-label, outcome-assessor-blinded, randomised controlled trial. Aboriginal children living in remote communities of the Northern Territory of Australia were eligible if they had previously completed the three-arm PREVIX_COMBO randomised controlled trial of the following vaccine schedules: three doses of a 13-valent PCV (PCV13; PPP) or a ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; SSS) given at 2, 4, and 6 months, or SSS given at 1, 2, and 4 months followed by PCV13 at 6 months (SSSP). At age 12 months, eligible children were randomly assigned by a computer-generated random sequence (1:1, stratified by primary group allocation) to receive either a PCV13 booster or a PHiD-CV10 booster. Analyses used intention-to-treat principles. Co-primary outcomes were immunogenicity against protein D and serotypes 3, 6A, and 19A. Immunogenicity measures were geometric mean concentrations (GMC) and proportion of children with IgG concentrations of 0·35 µg/mL or higher (threshold for invasive pneumococcal disease), and GMCs and proportion of children with antibody levels of 100 EU/mL or higher against protein D. Standardised assessments of otitis media, hearing impairment, nasopharyngeal carriage, and developmental outcomes are reported. These trials are registered with ClinicalTrials.gov (NCT01735084 and NCT01174849). FINDINGS: Between April 10, 2013, and Sept 4, 2018, 261 children were randomly allocated to receive a PCV13 booster (n=131) or PHiD-CV10 booster (n=130). Adequate serum samples for pneumococcal serology were obtained from 127 (95%) children in the PCV13 booster group and 126 (97%) in the PHiD-CV10 booster group; for protein D, adequate samples were obtained from 126 (96%) children in the PCV13 booster group and 123 (95%) in the PHiD-CV10 booster group. The proportions of children with IgG concentrations above standard thresholds in PCV13 booster versus PHiD-CV10 booster groups were the following: 71 (56%) of 126 versus 81 (66%) of 123 against protein D (difference 10%, 95% CI -2 to 22), 85 (67%) of 127 versus 59 (47%) of 126 against serotype 3 (-20%, -32 to -8), 119 (94%) of 127 versus 91 (72%) of 126 against serotype 6A (-22%, -31 to -13), and 116 (91%) of 127 versus 108 (86%) of 126 against serotype 19A (-5%, -13 to 3). Infant PCV13 priming mitigated differences between PCV13 and PHiD-CV10 boosters. In both groups, we observed a high prevalence of otitis media (about 90%), hearing impairment (about 75%), nasopharyngeal carriage of pneumococcus (about 66%), and non-typeable H influenzae (about 57%). Of 66 serious adverse events, none were vaccine related. INTERPRETATION: Low antibody concentrations 6 months post-booster might indicate increased risk of pneumococcal infection. The preferred booster was PCV13 if priming did not have PCV13, otherwise either PCV13 or PHiD-CV10 boosters provided similar immunogenicity. Mixed schedules offer flexibility to regional priorities. Non-PCV13 serotypes and non-typeable H influenzae continue to cause substantial disease and disability in Australian First Nation's children. FUNDING: National Health and Medical Research Council (NHMRC).

Interchangeability, immunogenicity and safety of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (Synflorix) and 13-valent-PCV (Prevenar13) schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial.

BACKGROUND: Aboriginal children living in remote communities are at high risk of early and persistent otitis media. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are primary pathogens. Vaccines with potential to prevent early OM have not been evaluated in this population. We compared immunogenicity (ELISA and opsonophagocytic activity) of a combination of Synflorix™ (PHiD-CV10, 10 serotypes and protein D of NTHi) and Prevenar13™ (PCV13, 10 serotypes plus 3, 6A, and 19A), with recommended schedules. METHODS: This open-label superiority trial randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to PCV13 (P) at 2-4-6 months (_PPP), PHiD-CV10 (S) at 2-4-6 months (_SSS), or PHiD-CV10 at 1-2-4 plus PCV13 at -6 months (SSSP). Primary outcomes (blinded) were immunogenicity against PCV13-only serotypes 3, 6A, 19A, and PHiD-CV10-only protein D at 7 months. Secondary outcomes include immunogenicity against all serotypes at 2, 4 and 7 months. FINDINGS: Between 2011 and 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(1 4 1). An intention to treat approach including all available data was used. The SSSP group had superior immunogenicity against serotypes 3, 6A, and 19A compared to _SSS (OPA GMT ratios 8.1 to 59.5, p < 0.001), and against protein D compared to _PPP (GMC ratio 11.9 (95%CI 9.7 to 14.6)). Immune responses to protein D and 3, 6A, and 19A in SSSP were not significantly lower (i.e. no harm) than either _SSS or _PPP. For ten common serotypes responses at 2, 4 and 7 months were superior for SSSP (following 1-, 2-, and 4- doses) than _SSS and _PPP (following 0-, 1-, and 3- doses). At 4 months, _SSS was superior to _PPP. Reactogenicity and hospitalisations were rare and unrelated to the intervention. INTERPRETATION: From two months, the 1-2-4-6-month combined schedule (SSSP) was safe and significantly more immunogenic than 2-4-6-month schedules. The earlier responses may be beneficial in high-risk populations.

Equitable access to dental care for an at-risk group: a review of services for Australian refugees.

OBJECTIVE: Despite the poor dental health of refugees, few specific services are available. This review maps public dental services for refugees across Australian jurisdictions, identifies gaps in provision, identifies barriers to accessing dental care, and provides recommendations for improving access and oral health promotion for this group. METHODS: Data were sought from the State and Territory services for: a) the survivors of torture; b) oral health care units; and c) auditors-general reports of dental services. Eligibility criteria and estimated waiting times for general dental services, criteria for access to emergency care and availability of interpreter services were reviewed. RESULTS: Marked variation exists across Australian jurisdictions in available dental services and criteria for access to public dental care for refugees. There is limited priority access to general dental services for refugees. Waiting times for public dental treatment in most, if not all, jurisdictions are unacceptably long (range 13-58 months). Few interpreter services exist for refugees seeking to access dental services. CONCLUSIONS: Access to dental services for refugees across Australia remains fragmented and limited, particularly in rural and regional areas. Refugees are not using services because of several barriers, including long waiting times, variation in assessment criteria, different eligibility criteria and limited interpreter services. Consequently, their pattern of service use does not accurately reflect their needs. IMPLICATIONS: Australia needs better co-ordinated, more extensive dental services that are easily accessible for this very high risk group. Identification of refugees as a special needs group and provision of targeted interventions addressing barriers to care are needed to establish adequate dental care.

Hiding from the sun - vitamin D deficiency in refugees.

BACKGROUND: It has been well established that women who wear a veil for cultural reasons and dark skinned migrants from Africa have an increased prevalence of vitamin D deficiency. Many refugee patients also come from countries where their skin is covered or they are indoors for most of the day. OBJECTIVE: This article explores the risk, diagnosis and management of vitamin D deficiency in the Australian refugee population. DISCUSSION: In 2004-2005, 75% of the 7000 refugees settling in Australia were from African countries and 20% were from the Middle East. Refugees may be exposed to less sunlight in Australia than in their country of origin because of an indoor lifestyle or an increased latitude. Refugee health centres confirm that vitamin D deficiency is present in 40-80% of refugee patients. Importantly, this is often asymptomatic. General practitioners are encouraged to test for vitamin D deficiency in refugees, especially as part of the initial health assessment.

Repeat pneumococcal polysaccharide vaccination does not impair functional immune responses among Indigenous Australians.

Indigenous Australians experience one of the highest rates of pneumococcal disease globally. In the Northern Territory of Australia, a unique government-funded vaccination schedule for Indigenous Australian adults comprising multiple lifetime doses of the pneumococcal polysaccharide vaccine is currently implemented. Despite this programme, rates of pneumococcal disease do not appear to be declining, with concerns raised over the potential for immune hyporesponse associated with the use of this vaccine. We undertook a study to examine the immunogenicity and immune function of a single and repeat pneumococcal polysaccharide vaccination among Indigenous adults compared to non-Indigenous adults. Our results found that immune function, as measured by opsonophagocytic and memory B-cell responses, were similar between the Indigenous groups but lower for some serotypes in comparison with the non-Indigenous group. This is the first study to document the immunogenicity following repeat 23-valent pneumococcal polysaccharide vaccine administration among Indigenous Australian adults, and reinforces the continued need for optimal pneumococcal vaccination programmes among high-risk populations.

Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness.

BACKGROUND: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. METHODS: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3µg/ml but <4.0µg/ml; or a post-vaccination antibody concentration >4.0µg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose. RESULTS: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of serotypes with a positive response. CONCLUSION: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.

Hurdles to health: immigrant and refugee health care in Australia.

Refugees and asylum seekers face a number of barriers to accessing health care and improved health status. These include language difficulties, financial need and unemployment, cultural differences, legal barriers and a health workforce with generally low awareness of issues specific to refugees. Importantly, current Australian government migration and settlement policy also impacts on access to health and health status. An adequate understanding of these 'hurdles to health' is a prerequisite for health providers and health service managers if they are to tailor health care and services appropriately. We include tables of available resources and entitlements to health care according to visa category to assist providers and managers.

Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial.

INTRODUCTION: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection. METHODS AND ANALYSES: This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM. ETHICS AND DISSEMINATION: Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals. TRIAL REGISTRATION NUMBERS: ACTRN12610000544077 and NCT01174849.

Hospital health care worker (HCW) vaccination coverage after implementation of an HCW vaccination policy.

The purpose of this study was to assess knowledge, attitudes, practices, and self-reported vaccination status of HCWs at a tertiary Australian hospital, one year after implementation of a HCW vaccination policy. Two cross-sectional telephone surveys were conducted with HCWs at the hospital prior to and one year after HCW vaccination policy implementation. There was a 95% (272/287) response rate from eligible HCWs in the follow-up survey. Despite 96% (260/272) of HCWs indicating a willingness to update their vaccination status, only 24% (65/272) reported being fully vaccinated. Successful policy implementation requires adequate resource allocation and organisational commitment. Ongoing evaluation can inform the success of this process.