Safety of Hepatitis B Vaccines (Monovalent or as Part of Combination) in Preterm Infants: A Systematic Review.

Introduction: The World Health Organization (WHO) recommends vaccination against hepatitis B as soon as possible following birth for all infants, regardless of prematurity. Hepatitis B vaccination at birth is clearly justified, represents a crucial step in the global control of perinatally acquired hepatitis B and there are no safety concerns in infants born at term. However, there is limited information on the safety of the hepatitis B vaccine in preterm infants, whose immune responses and morbidity risk differ from those in infants born at term. Objectives: The objectives of this paper are to systematically review the literature regarding the safety and risk of adverse events following immunisation (AEFIs) associated with the administration of the hepatitis B vaccine (monovalent or as part of a combination vaccine) to preterm infants. Methods: We performed a search for relevant papers published between 1 January 2002 and 30 March 2023 in the Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials and CINAHL Plus databases. Two authors independently reviewed and analysed each article to include in the systematic review. Narrative synthesis is presented. Results: Twenty-one relevant papers were identified and included in this systematic review. The vast majority of data pertained to multi-antigen (combination) vaccine preparations and vaccination episodes from 6 weeks of age onwards. We found no publications investigating the timing of the birth dose of the hepatitis B vaccine, and AEFI reporting was exclusively short-term (hours to days following administration). There was substantial variability in the reported rate of AEFIs between studies, ranging from 0% to 96%. Regardless of frequency, AEFIs were mostly minor and included injection site reactions, temperature instability and self-limiting cardiorespiratory events. Six studies reported serious adverse events (SAEs) such as the requirement for escalation of respiratory support. However, these occurred predominantly in high-risk infant populations and were rare (~1%). Using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, the certainty of evidence was assessed as very low. Conclusions: Despite substantial variability between the relatively small number of published studies in terms of cohort selection, definitions, vaccine preparations and reporting, hepatitis B-containing vaccines (mostly as combination vaccines) appear to be relatively well tolerated in preterm infants from 6 weeks of age. Research focusing on the safety of hepatitis B vaccine in preterm infants specifically within 7 days of birth is lacking, particularly regarding long-term morbidity risk. Further research in this area is required.

A multicentre, retrospective audit of fosfomycin use for urinary tract infections in Australian children and adolescents.

BACKGROUND: Urinary tract infections (UTIs) due to MDR organisms are increasingly common. The lack of paediatric data on efficacious antibiotics makes UTI treatment particularly challenging. Data on the efficacy of fosfomycin use for UTI in children are variable. METHODS: We conducted a retrospective audit of children aged 0-18 years who were treated with fosfomycin for UTI at seven tertiary paediatric hospitals in Australia over a 7 year period, from 2014 to 2020. RESULTS: Ninety-one children with a median age of 5 years (range 2 months to 18 years) received oral fosfomycin for UTI. The majority (57/91, 63%) had one or more comorbidity, with the most common being renal tract anomalies (24/91, 26%). Fifty-nine (65%) had febrile UTI, 14/91 (15%) had pyelonephritis and 1/91 (1%) was bacteraemic. A majority (80/91, 88%) of urinary cultures had an ESBL-producing Gram-negative pathogen isolated. Fosfomycin susceptibility was evident in all 80 isolates tested. For uncomplicated UTI, the most common dose in children aged <1, 1-12 and >12 years was 1, 2 and 3 g, respectively. For complicated UTI, doses of 2 and 3 g were most common. The median duration of fosfomycin administration was 5 days (range 1-82). Clinical cure was achieved in 84/90 (93%); the six with treatment failure had underlying comorbidities. Overall, 2/91 (2%) children experienced drug-related adverse effects comprising gastrointestinal symptoms in both, which resolved after treatment discontinuation. CONCLUSIONS: Fosfomycin is well tolerated and associated with favourable treatment outcomes in children with UTI. Further research on the optimal dosing strategy is required.

An Approach to the Treatment of Children With COVID-19.

There are limited data to guide treatment recommendations for children with acute, symptomatic coronavirus disease 2019 (COVID-19). This review outlines a proposed management approach for children based on the published evidence to date and the approval of medications through drug regulatory agencies, as well as the known safety profile of the recommended drugs in this age group.

Feasibility and acceptability of targeted salivary cytomegalovirus screening through universal newborn hearing screening.

AIM: This study aimed to determine the feasibility and parental acceptability of screening for congenital cytomegalovirus (cCMV) through saliva polymerase chain reaction in infants who did not pass their newborn hearing screening. Additionally, the utility (i.e. time to diagnosis and treatment) of this enhanced clinical pathway was evaluated. METHODS: The study was conducted through the Victorian Infant Hearing Screening Programme (VIHSP) across four maternity hospitals in Melbourne, Australia, during June 2019-March 2020. Parents were approached by VIHSP staff about obtaining a test for cytomegalovirus (CMV) at the time of their baby's second positive ('refer') result on the VIHSP screen. Participating parents collected a saliva swab for CMV polymerase chain reaction from their infants. Feasibility was determined by the proportion of 'referred' infants whose parents completed the salivary CMV screening test ≤21 days of life. Acceptability was measured through parent survey. RESULTS: Of 126 eligible families, 96 (76.0%) had salivary screening swabs taken ≤21 days of life. Most families (>92.0%) indicated that screening was acceptable, straightforward and thought testing their baby for cCMV was a good idea. One infant screened positive on day 30, was diagnosed with cCMV via confirmatory testing by day 31 and commenced valganciclovir on day 32. CONCLUSIONS: Obtaining a saliva sample to screen for cCMV in infants who do not pass their newborn hearing screen is feasible and appears acceptable to parents. This targeted cCMV screening method could be an option where mothers are rapidly discharged from hospital, especially in the context of the COVID-19 pandemic.

Infliximab for Paradoxical Reactions in Pediatric Central Nervous System Tuberculosis.

Paradoxical reactions in central nervous system tuberculosis (CNS-TB) are associated with significant morbidity and mortality. We describe 4 HIV-uninfected children treated for CNS-TB with severe paradoxical reactions unresponsive to corticosteroids. All made recovery after treatment with infliximab, highlighting the safety and effectiveness of infliximab for this complication, and need for prospective trials.

Elimination of typhoid: Possibility or pipe dream?

The elimination of typhoid would have a substantial impact on the health of millions of people living in South and Southeast Asia and sub-Saharan Africa. Like many diseases before it, there are significant challenges to elimination, including access to safe drinking water and adequate sanitation practices, the availability of a vaccine, the identification and management of chronic carriers and the emergence of anti-microbial resistance. While provision of clean water and adequate sanitation must remain the ultimate goal, in the short term, required to cornerstone elimination in endemic areas, is an efficacious vaccine. Recent evidence of effectiveness with a tetanus-toxoid conjugate vaccine offers an opportunity for an immunogenic and safe vaccine able to be delivered to young children. Shown to be efficacious in Nepal, where infection is endemic, it may be a viable option in public health programmes moving towards elimination.

Hepatitis B Testing: Old Tricks for Newborn Players.

We describe 2 preterm neonates with transient hepatitis B surface (HBs) antigenemia detected after Hepatitis B vaccination. Repeat serology in both cases tested negative for hepatitis B surface antigen, confirming transient HBs antigenemia. The duration of transient HBs antigenemia affirms current literature in the pediatric population.

Does discharging asthma patients after one hour of treatment if clinically well affect emergency department length of stay.

AIM: Asthma is a major contributor to direct and indirect health-care costs and resource use. In May 2015, the Royal Children's Hospital (RCH) amended its clinical practice guideline for acute asthma management from discharging patients if the anticipated salbutamol requirement was every 3-4 h to discharging patients who were clinically well at 1 h after initial treatment. Our objective was to examine the impact of the new discharge recommendation on emergency department (ED) length of stay (LOS), rates of admission and representation. METHODS: We retrospectively audited the case notes of children presenting with mild or moderate asthma to the RCH ED over the equivalent 2-week periods in winter 2014 (pre-implementation of the new guideline) and 2015 (post-implementation). RESULTS: A total of 105 patients in 2014 and 92 patients in 2015 were included. In both years, all patients who initially presented with mild or moderate asthma either improved or stayed within the same severity classification at the 1-h assessment. For patients who were clinically well by the 1-h assessment, there was a significant reduction in admissions between 2014 and 2015 (40 vs. 10%, P = 0.001). There was also a reduction for these patients in median LOS from 3 h 13 min in 2014 to 2 h 31 min in 2015 (P = 0.03). In both years, all patients who were moderate at 1 h were admitted. There was no difference in the rate of representation or subsequent deterioration in those patients who were discharged at 1 h between the 2 years. CONCLUSION: Early discharge of patients who are clinically well 1 h after initial therapy may be associated with a reduction in LOS and admission rate without an apparent compromise in patient safety. Further evaluation of this intervention is required to determine whether this is a true causal relationship.

Rural health service managers' perspectives on preparing rural health services for climate change.

OBJECTIVE: To determine health service managers' (HSMs) recommendations on strengthening the health service response to climate change. DESIGN: Self-administered survey in paper or electronic format. SETTING: Rural south-west of New South Wales. PARTICIPANTS: Health service managers working in rural remote metropolitan areas 3-7. MAIN OUTCOME MEASURES: Proportion of respondents identifying preferred strategies for preparation of rural health services for climate change. RESULTS: There were 43 participants (53% response rate). Most respondents agreed that there is scepticism regarding climate change among health professionals (70%, n = 30) and community members (72%, n = 31). Over 90% thought that climate change would impact the health of rural populations in the future with regard to heat-related illnesses, mental health, skin cancer and water security. Health professionals and government were identified as having key leadership roles on climate change and health in rural communities. Over 90% of the respondents believed that staff and community in local health districts (LHDs) should be educated about the health impacts of climate change. Public health education facilitated by State or Federal Government was the preferred method of educating community members, and education facilitated by the LHD was the preferred method for educating health professionals. CONCLUSIONS: Health service managers hold important health leadership roles within rural communities and their health services. The study highlights the scepticism towards climate change among health professionals and community members in rural Australia. It identifies the important role of rural health services in education and advocacy on the health impacts of climate change and identifies recommended methods of public health education for community members and health professionals.

The Impact of Systematic Point-of-Care Ultrasound on Management of Patients in a Resource-Limited Setting.

Although target point-of-care (POC) ultrasonography has been shown to benefit patients in resource-limited settings, it is not clear whether a systematic POC ultrasound assessment in these settings can also lead to similar changes in patient management. A predefined systematic set of POC ultrasound scans were performed on inpatients at a tertiary referral hospital in Tanzania to see if this resulted in changes to patient management. Of the 55 patients scanned, an abnormality was detected in 75% (N = 41), and a change in patient management was recommended or implemented on the basis of POC ultrasound findings in 53% (N = 29). The main impact was earlier initiation of treatment due to more rapid and accurate diagnosis. Further research is warranted to determine whether systematic POC ultrasonography would result in improved patient outcomes in resource-limited settings.

Supports for medical students during rural clinical placements: factors associated with intention to practise in rural locations.

INTRODUCTION: Through rural clinical schools (RCSs), medical students may undertake an extended block of clinical training in rural Australia. The premise of these placements is that meaningful rural exposure will facilitate rural career uptake. RCSs offer a range of supports to facilitate student engagement in the program. This study aims to analyse RCS students' perceptions of these supports and impact on intentions to work rurally. METHODS: Between September 2012 and January 2013 RCS students were invited to complete questions regarding perceptions of student support, as a part of the annual Federation of Australian Medical Educators survey. Multivariable logistic regression was used to identify associations between supports and intentions for rural internship or career. RESULTS: There were 454 participants. A majority of students (n=349, 79.1%) felt well supported by their RCS. Students from a rural background (odds ratio (OR)=1.64 (95% confidence interval (CI):1.13-2.38)), or who indicated that their placement had a positive impact on their wellbeing (OR=1.38 (95%CI:1.07-1.80)), were more likely to intend to complete a rural internship. Those who felt socially isolated were less likely to elect this (OR=0.82 (0.70-0.97)). Outcomes were similar for those indicating a preference for rural or remote practice after completing training. CONCLUSIONS: Student perceptions of supports offered by RCSs were generally very positive. Perceptions of financial support were not predictive of rural career intent. Although this does not negate the importance of providing appropriate financial supports, it does demonstrate that student wellbeing is a more important recruitment factor for rural practice.

Preparing rural general practitioners and health services for climate change and extreme weather.

OBJECTIVE: To determine the knowledge and recommendations of rural general practitioners (GPs) in regard to climate change and the preparedness of rural health services for its health impacts. DESIGN: A quantitative descriptive survey distributed in paper-based or electronic form. SETTING: Rural Southwest of New South Wales. PARTICIPANTS: GPs and GP registrars working in Rural Remote Metropolitan Areas (RRMA) 3-7. MAIN OUTCOME MEASURES: Questionnaire responses analysed with descriptive statistics and inferential tests. RESULTS: While the majority of respondents agreed with statements supporting climate science and the impact of climate change on health, between 24% and 34% of respondents were unsure or did not agree. Furthermore, between 33% and 44% of GP respondents working in RRMA 5-7 were unsure or did not agree that their health service had the capacity to provide an initial response to an extreme weather event (P = 0.01). Strengthening health service acute disaster capacity response was a preferred adaptation strategy for improving health service preparedness of 61% of participants. A greater proportion of GPs were supportive of their role as advocates on general health issues (80%) compared with extreme weather events (60%) or climate change and health (63.5%) (P ≤ 0.01). For professional development and education, 71% preferred a locally based workshop or seminar. CONCLUSIONS: The study highlights the need to consider closely the views of GPs when preparing rural communities for the possible health effects of climate change. Findings indicate concern for health service preparedness, particularly in smaller rural communities. Further development of disaster response planning and communication is needed.