Button battery exposure in children: a systematic review and meta-analysis.

BACKGROUND: There is a rising burden of severe and fatal outcomes resulting from button battery exposures (ingestions or insertions). We summarised current evidence following button battery exposures in children and provided pooled prevalence estimates for key clinical characteristics, complications and risk estimates for predictors. METHODS: MEDLINE, Embase and Scopus databases were searched up to 19 May 2023. Included studies described complications of button battery exposures in children aged <18 years and reported prevalence data, an OR estimate or allowed OR calculation. Random effects models were used to estimate pooled estimates and event rates. FINDINGS: Forty-four articles (3125 children) were included in the analysis. Battery exposures were more common in males (59%) and young children. For ingestions, batteries were most often located in the stomach (43%). Mucosal damage (46%) and oesophageal stricture (10%) were the most common complications. Most (60%) children were asymptomatic at presentation. When symptoms were present, vomiting (26%) and dysphagia (18%) were the most common. Duration of ingestion to removal increased the likelihood of any complication; OR 3.71 (95% CI 1.11 to 12.42) for ≥10 hours and 5.12 (95% CI 1.79 to 14.67) for ≥12 hours. Battery diameter ≥20 mm was associated with any complication OR 4.34 (95% CI 1.16 to 16.27) and oesophageal location OR 18.66 (95% CI 6.99 to 49.82). Death was associated with oesophageal impaction OR 15.52 (95% CI 2.40 to 100.27). For insertions, nasal septal perforation was the most common complication (13%). INTERPRETATION: Button batteries are a potentially fatal domestic hazard particularly for young children. Increased prevention efforts through safer battery design are needed to mitigate this risk.

Fluoxetine antagonizes the acute response of LPS: Blocks K2P channels.

The channels responsible for maintaining resting membrane potential are known as K2P (two-P-domain K+ subunit) channels, a subset of which are known to be blocked by Fluoxetine. In this experiment, the compound's effects on the membrane potential were examined on muscles in larval Drosophila overexpressing a subtype of K2P channel (known in Drosophila as dORKA1 or ORKA1) and compared to larvae without overexpression. The compound was also observed in sequence and/or combination with a form of lipopolysaccharide (LPS) that transiently activates K2P channels. Different concentrations of Fluoxetine were tested, and it was also examined in cocktail with the LPS. At 25 µM Fluoxetine exposure, muscle in control larvae underwent depolarization, while muscles overexpressing K2P channels hyperpolarized; at 50 µM, however, much more variable responses were observed. The LPS caused hyperpolarization in both larval strains, but the effect was more transient in the Canton-S line than in the K2P overexpressors. Finally, LPS continued to cause hyperpolarization even in the presence of Fluoxetine, while Fluoxetine quickly depolarized the muscle during exposure to LPS. The cocktail showed a smaller effect on muscles overexpressing ORKA1 as compared to the controls, indicating that Fluoxetine does not block the ORKA1 subtype. This study is significant because it demonstrates how overexpression of K2P channels alters membrane response to LPS and Fluoxetine exposure.

The Best Start Trial: A randomised controlled trial of ultra-early parent-administered physiotherapy for infants at high risk of cerebral palsy or motor delay.

BACKGROUND: It is unknown whether ultra-early physiotherapy commenced during neonatal intensive care unit admission is of value for optimising developmental outcomes in preterm/term infants at high-risk of cerebral palsy or motor-delay. AIMS: To determine whether ultra-early parent-administered physiotherapy to preterm/term high- risk infants commenced at earliest from 34-weeks post menstrual age, improves motor outcomes at 16-weeks corrected age (CA) compared to usual care. METHODS: Single-blind randomised controlled pilot study with 30 infant participants. The primary outcome was the Alberta Infant Motor Scale (AIMS) total score at 16-weeks CA. Secondary outcomes included (i) parent Depression Anxiety and Stress Score and Parent Perceptions Survey at 16-weeks CA; and (ii) Bayley Scales of Infant Development at 12-months CA. RESULTS: There were no clinically worthwhile effects at 16-weeks CA on the AIMS (mean between-group difference, 95% CI: -0.2, -2.4 to 2.0) or most secondary outcomes. However, the parents' "perception of treatment effectiveness" and "perception of change" favoured the experimental group. CONCLUSIONS: In this pilot trial, there was no clinically worthwhile effect of ultra-early parent-administered physiotherapy over usual care on the AIMS. However, the intervention was feasible for infants, acceptable to parents and parents perceived a benefit of treatment. Whilst this trial did not demonstrate treatment effectiveness using the AIMS, these findings should be interpreted cautiously because of the small sample size, the low responsivity of the AIMS to change in motor performance and the heterogeneity of the participants. Therefore, the intervention should not be abandoned on the basis of this trial, but rather further evaluated in a larger trial that addresses some of the learnings from this one.

Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species.

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in newborn pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.

Drinking excessive amounts of alcohol during pregnancy can cause foetal alcohol spectrum disorder and other conditions in children that affect their physical and mental development. Many countries advise women who are pregnant or trying to conceive to avoid drinking alcohol entirely. However, surveys of large groups of women in Western countries indicate that most women continue drinking low to moderate amounts of alcohol until they discover they are pregnant and then stop consuming alcohol for the rest of their pregnancy. It remains unclear how this common drinking pattern affects the foetus. The instructions needed to build and maintain a human body are stored within molecules of DNA. Some regions of DNA called genes contain the instructions to make proteins, which perform many tasks in the body. Other so-called 'non-coding' regions do not code for any proteins but instead have roles in regulating gene activity. One way cells control which genes are switched on or off is adding or removing tags known as methyl groups to certain locations on DNA. Previous studies indicate that alcohol may affect how children develop by changing the patterns of methyl tags on DNA. To investigate the effect of moderate drinking during the early stages of pregnancy, Bestry et al. exposed pregnant mice to alcohol and examined how this affected the patterns of methyl tags on DNA in their offspring. The experiments found moderate levels of alcohol were sufficient to alter the patterns of methyl tags in the brains and livers of the newborn mice. Most of the changes were observed in non-coding regions of DNA, suggesting alcohol may affect how large groups of genes are regulated. Fewer changes in the patterns of methyl tags were found in mice whose mothers had diets rich in two essential nutrients known as folate and choline. Further experiments found that some of the affected mouse genes were similar to genes linked to foetal alcohol spectrum disorder and other related conditions in humans. These findings highlight the potential risks of consuming even moderate levels of alcohol during pregnancy and suggest that a maternal diet rich in folate and choline may help mitigate some of the harmful effects on the developing foetus.

The Effect of Calcium Ions on Resting Membrane Potential.

Regulating membrane potential is key to cellular function. For many animal cells, resting membrane potential is predominantly driven by a family of K2P (two-pore domain) potassium channels. These channels are commonly referred to as leak channels, as their presence results in the membrane being permeable to K+ ions. These channels, along with various pumps and exchangers, keep the cell resting membrane potential (Rp) relatively close to potassium's equilibrium potential (EK); however, in many cells, the resting membrane potential is more depolarized than the EK due to a small Na+ ion leak. Raising [Ca2+]O (extracellular Ca2+ concentration) can result in hyperpolarization of the membrane potential from the resting state. The mechanism for this hyperpolarization likely lies in the blockage of a Na+ leak channel (NALCN) and/or voltage-gated Na+ channels. The effects may also be connected to calcium-activated potassium channels. Using Drosophila melanogaster, we here illustrate that changing [Ca2+]O from 0.5 to 3 mM hyperpolarizes the muscle. Replacing NaCl with LiCl or choline chloride still led to hyperpolarization when increasing [Ca2+]O. Replacing CaCl2 with BaCl2 results in depolarization. K2P channel overexpression in the larval muscle greatly reduces the effects of [Ca2+]O on cell membrane potential, likely because potential is heavily driven by the EK in these muscles. These experiments provide an understanding of the mechanisms behind neuronal hypo-excitability during hypercalcemia, as well as the effects of altered expression of K2P channels on membrane potential.

Community engagement and local governance for health equity through trust: lessons from developing the CONNECT Initiative in the Lao People's Democratic Republic.

Community engagement and local governance are important components of health interventions aiming to empower local populations. Yet, there is limited evidence on how to effectively engage with communities and codevelop interventions, especially in Southeast Asian contexts. Despite rapid progress, the Lao People's Democratic Republic (Lao PDR) still has high maternal and child mortality, with essential service coverage showing significant disparities across socioeconomic strata. Long-standing challenges in community health were exacerbated by the COVID-19 pandemic and reinforced by poor trust between users and health providers. However, the pandemic also provided an opportunity to develop approaches for enhanced community engagement and local governance capacity to tackle health inequities. The Community Network Engagement for Essential Healthcare and COVID-19 Responses through Trust (CONNECT) Initiative, developed by the Lao PDR government, WHO and partners, has resulted in initial positive outcomes in community health such as increased vaccination uptake, facility births and trust in health providers. This case study describes the iterative, adaptive process by which the CONNECT Initiative was developed, and how the core components, key stakeholders, theory of change and evaluation framework evolved from grounded observations and hypotheses. Lessons learnt include (1) awareness of entry points and existing structures to strengthen local governance for health through mutually beneficial intersectoral collaboration; (2) building relationships and trust with an adaptive, grounds-up approach for sustainability and scalability. As a model which can be adapted to other settings, this case study provides evidence on how to engage with communities, strengthen local governance and codevelop interventions towards greater health equity.

"Sustaining NSW Families" as a hybrid face-to-face/virtual program: Experiences of clients and clinicians.

To explore clients' and clinicians' perspectives about the acceptability and perceived outcomes of the Sustaining New South Wales (NSW) Families (SNF) program shifted to a hybrid service delivery model during the COVID-19 pandemic. Mixed methods design comprising cross-sectional online surveys and a focus group. Eighty clients who accessed the SNF service and 12 SNF clinicians. Anonymous client survey comprising questions about perceived benefits and impacts of the hybrid SNF program model, and suggestions for change. Clinician focus group discussion about perceived benefits and challenges of the hybrid SNF model. The hybrid SNF program is a child and family health nursing home visitation program for families with moderate level psychosocial risks. It comprises a mix of face-to-face and virtual telehealth/telephone appointments, delivered during pregnancy and up to 2 years postpartum. Clients reported high levels of satisfaction with the program, and improvements in confidence and decision-making. Clinicians spoke of increased efficiency and flexibility, and capacity for ongoing service provision during the COVID-19 period. Technology access issues were identified as a barrier. Overall, however, both clients and clinicians expressed a preference for face-to-face SNF service provision. While further studies are required to test clinical outcomes, the hybrid SNF model is acceptable to clients and clinicians.

Complications of button battery ingestion or insertion in children: a systematic review and pooled analysis of individual patient-level data.

BACKGROUND: Button battery (BB) exposures are common in children and can have devastating consequences. We reviewed current evidence on the complications associated with BB exposure and identified predictors of outcomes using individual patient-level data. DATA SOURCES: We carried out a systematic review and pooled analysis by searching MEDLINE, Embase, and Scopus up to May 19, 2023. Included studies describe complications following BB exposures in children (aged < 18 years). Odds ratios (ORs) were calculated using binary logistic regression to measure associations between predictive factors and different outcomes. RESULTS: Two-hundred seventeen studies (439 children) were included. The median age at presentation was 1.75 [interquartile range (IQR) 1.00-3.00] years and 399 (90.9%) exposures were ingestions. Of the 380 cases reporting sex, 162 (42.6%) were female. Feeding (192, 48.1%) and respiratory difficulties (138, 34.6%) were common presenting features for ingestions, while symptomatology was site-specific for insertions. Common complications included oesophageal mucosal damage alone (105, 26.3%) and tracheooesophageal fistula (93, 23.3%) for ingestions, and nasal septal perforation (22, 55.0%) and mucosal damage alone (13, 32.5%) for insertions. Intestinal perforation occurred in 2.5% of ingestion cases, including perforation of Meckel's diverticulum, peritonitis, and jejunocolic fistula. Vascular complications were common among children who died. Age (≤ 2 years), battery exposure duration (> 6 hours), and battery diameter (≥ 20 mm) were associated with common and severe complications of ingestions. CONCLUSION: BB injuries are time-critical, with severe sequelae predominantly affecting young children. Diagnosis is challenging. Preventative work through regulation and safer battery design are required to eliminate this problem.

Community engagement for stakeholder and community trust in healthcare: Short-term evaluation findings from a nationwide initiative in Lao PDR.

BACKGROUND: Trust remains a critical concept in healthcare provision, but little is known about the ability of health policy and interventions to stimulate more trusting relationships between communities and the health system. The CONNECT (Community Network Engagement for Essential Healthcare and COVID-19 Responses Through Trust) Initiative in Lao PDR provided an opportunity to assess the community-level impact of a trust-building community engagement approach. METHODS: A mixed-method process evaluation was implemented from 10/2022-12/2023 among 14 diverse case study communities in four provinces across Lao PDR. Data collection involved two rounds of census surveys (3161 observations incl. panel data from 618 individuals) including an 8-item trust scale, 50 semi-structured interviews with villagers, and 50 contextualizing key informant interviews. The two data collection rounds were implemented before and three months after village-based CONNECT activities and helped discern impacts among activity participants, indirectly exposed villagers, and unexposed villagers in a difference-in-difference analysis. RESULTS: Stakeholders attested strong support for the CONNECT Initiative although community-level retention of trust-related themes from the activities was limited. Quantitative data nevertheless showed that, at endline, the 8-item trust index (from [-8 to +8]) increased by 0.95 points from 4.44 to 5.39 and all trust indicators were universally higher. Difference-in-difference analysis showed that villagers exposed to the CONNECT activities had a 1.02-index-point higher trust index compared to unexposed villagers. Trust impacts improved gradually over time and were relatively more pronounced among men and ethnic minority groups. CONCLUSIONS: The CONNECT Initiative had considerable direct and systemic effects on community members' trust in their local health centers in the short term, which arose from strong stakeholder mobilization and gradual institutional learning. Relational community engagement approaches have the potential to create important synergies in health policy and broader cross-sectorial strategies, but also require contextual grounding to identify locally relevant dimensions of trust.

Fetal alcohol spectrum disorder resources for health professionals: a scoping review.

OBJECTIVES: This scoping review aimed to identify and critically appraise resources for health professionals to identify, diagnose, refer, and support individuals with fetal alcohol spectrum disorder (FASD)-including the extent to which the resources are appropriate for use in communities with First Nations Peoples. METHOD: Seven peer-reviewed databases (April 2022) and 14 grey literature websites (August 2022) were searched. The reference lists of all sources that underwent full-text review were handsearched, and FASD experts were consulted for additional sources. Resources were assessed using the Appraisal of Guidelines for REsearch and Evaluation II instrument and an adapted version of the National Health and Medical Research Council FORM Framework and iCAHE Guideline Quality Checklist. RESULTS: A total of 41 resources underwent data extraction and critical appraisal, as screening and/or diagnosis guidelines were excluded because they are covered in other reviews. Most were recently published or updated (n=24), developed in the USA (n=15, 36.6%) or Australia (n=12, 29.3%) and assisted with FASD patient referral or support (n=40). Most management guidelines scored 76%-100% on overall quality assessment (n=5/9) and were recommended for use in the Australian context with modifications (n=7/9). Most of the guides (n=15/22) and factsheets (n=7/10) received a 'good' overall score. Few (n=3/41) resources were explicitly designed for or with input from First Nations Australians. CONCLUSION: High-quality resources are available to support health professionals providing referrals and support to individuals with FASD, including language guides. Resources should be codesigned with people living with FASD to capture and integrate their knowledge and preferences.

Formulating policies and procedures for managing diving related deaths: a whole of state engagement from frontline and hospital services in Tasmania.

Introduction: Tasmania is a small island state off the southern edge of Australia where a comparatively high proportion of the 558,000 population partake in recreational or occupational diving. While diving is a relatively safe sport and occupation, Tasmania has a significantly higher diving death rate per head of population than other States in Australia (four times the national diving mortality rate). Methods: Three compressed gas diving deaths occurred in seven months between 2021-2022 prompting a review of the statewide approach for the immediate response of personnel to diving-related deaths. The review engaged first responders including the Police Marine and Rescue Service, hospital-based departments including the Department of Hyperbaric and Diving Medicine, and the mortuary and coroner's office. Results: An aide-mémoire for all craft groups, digitalised checklists for first responders (irrespective of diving knowledge), and a single-paged algorithm to highlight inter-agency communication pathways in the event of a diving death were designed to enhance current practices and collaboration. Conclusions: If used, these aids for managing diving related deaths should ensure that time-critical information is appropriately captured and stored to optimise information provided for the coronial investigation.

Reaching the unreached through building trust: a mixed-method study on COVID-19 vaccination in rural Lao PDR.

INTRODUCTION: The global COVID-19 vaccine rollout has been impacted by socioeconomic disparities and vaccine hesitancy, but few studies examine reasons for changed attitudes. In Lao People's Democratic Republic (Lao PDR), a nationwide government-led initiative was developed in response to COVID-19, focused on community health ownership and trust in primary healthcare. The intervention team including health and governance sectors conducted capacity-building workshops with local staff and community representatives and visited villages for vaccination outreach. This study investigates the impact of this intervention on COVID-19 vaccine acceptance in rural communities. METHODS: Conducted in Xiengkhuang province, Lao PDR, from December 2022 to February 2023, the study employed a sequential mixed-methods research design. Data on vaccinated individuals from 25 villages were collected from 11 primary healthcare units; pre-post analysis was applied. Qualitative data, gathered through interviews and focus group discussions with villagers, village authorities, health staff and local government (n=102) in six villages, underwent inductive thematic analysis. RESULTS: First-dose vaccine uptake after the intervention increased significantly (6.9 times). Qualitative analysis identified key reasons for vaccination hesitancy: (1) mistrust due to rumours and past experiences; (2) poor communication and inconsistent messaging and (3) challenges in access for priority groups. Influencing factors during the intervention included (1) effective local-context communication; (2) leveraging existing community structures and influential individuals in a multisectoral approach and (3) increased community motivation through improved satisfaction, ownership and relationships. CONCLUSION: This study highlights the impact and methods of building trust with unreached populations in health interventions, emphasising locally led solutions. Successful reversal of vaccine hesitancy was achieved by addressing root causes and fostering ownership at community and local government levels through a 'positive approach'. This diverges from conventional supplemental immunisation activities and holds potential for systematically building trust between unreached populations and health systems. Further research could explore the impacts of routine vaccination for sustained improvements in health equity.

Evaluation of the Fetal Alcohol Spectrum Disorder Hub Australia website.

INTRODUCTION: To evaluate use and utility of the Fetal Alcohol Spectrum Disorder (FASD) Hub Australia website. METHODS: Online REDCap user survey incorporating the Website Evaluation Questionnaire, open ended questions, Google metrics data and an accessibility audit. RESULTS: Seventy-six participants: researchers (32%), health professionals (29%) and policymakers/advocates (16%) completed the survey. Most were from Australia (95%) and were likely or very likely to recommend the FASD Hub to colleagues (92%), friends (74%) and patients (72%). The mean Website Evaluation Questionnaire score was at least 3.45/5 for all dimensions (ease of use, hyperlinks, structure, relevance, comprehension, completeness, layout, search option); range 3.45 (search option) to 4.04 (relevance). Participants found the content trustworthy (92%) but wanted more information for, and to support, Aboriginal and Torres Strait Islander peoples, and improved search capacity. Google metrics identified 25,534 unique users over 6 months (82% new users); 83% aged 18-44 years, 72% female and 35% international. CONCLUSIONS: Users found the FASD Hub accessible, authoritative and useful and suggested improvements.

Trust in healthcare: methodological and conceptual insights from mixed-method research in Lao People's Democratic Republic.

BACKGROUND: Global health foregrounds trust as a key requirement for the achievement of international health initiatives, but it remains an elusive concept that is often mobilised without consideration of its dimensions, drivers and downstream behavioural consequences. This paper aims to contribute to the conceptual development and measurement of 'patient trust in primary healthcare' from the lower middle-income country perspective of rural Lao PDR. METHODS: A two-phase mixed-method research design was implemented between January 2021 and April 2023. Phase 1 involved exploratory qualitative research to understand the local expressions and dimensions of patient trust in primary healthcare, with 25 semistructured interviews and 17 focus group discussions (120 participants) in eight villages in Bokeo Province. Phase 2 involved explanatory research to assess patterns of trust systematically at scale in 14 villages across four provinces, wherein 26 cognitive interviews, 17 expert interviews and non-participant community observations informed a community census survey with 1838 participants. We analysed qualitative data through content-oriented thematic analysis and developed an 8-item trust scale on that basis. Quantitative data analysis used descriptive statistical and regression analysis. RESULTS: We found that trust in primary healthcare is readily understood and intrinsically valuable in rural Lao PDR. Key dimensions included communication, respectful care, relationship, fairness, integrity, reputation, assurance of treatment and competence. The survey highlighted that reputation, competence, integrity and respectful care had the lowest trust scores. Health centre operations predicted the local expressions of trust. The behavioural consequences of trust were limited to a positive statistical association with antenatal care uptake among pregnant women but outweighed by alternative measures that also captured the availability of healthcare facilities. CONCLUSIONS: Overall, the development of our quantitative trust scale offers a process model for future researchers. We conclude that interpersonal, institutional and service-related trust require more explicit recognition in health system development and integration into health policy.

Maternal perinatal social support and infant social-emotional problems and competencies: a longitudinal cross-cohort replication study.

PURPOSE: Maternal perinatal social support is theorised to promote offspring social-emotional development, yet few studies have prospectively examined this relationship. Findings may inform preventative intervention efforts, to support a healthy start to emotional life. METHODS: This study examined whether maternal social support perinatally predicts infant social-emotional development at 12 months of age in two longitudinal cohort studies: The Australian Temperament Project (ATP) (n = 1,052 mother-infant dyads [653 mothers, M age_at_birth = 32.03, 88% Australian-born; 1,052 infants, 52% girls]) and The Triple B Pregnancy Cohort Study (Triple B) (n = 1,537 dyads [1,498 mothers, M age_at_birth = 32.53, 56% Australian-born; 1,537 infants, 49% girls]). Social support was assessed at pregnancy (third trimester) and eight-weeks post-birth. Infant social-emotional competencies (ATP: Brief Infant and Toddler Social and Emotional Assessment (BITSEA), Competencies Scale; Triple B: Bayley Scales of Infant and Toddler Development-Social Emotional Scale) and problems (ATP: BITSEA, Problems Scale; Triple B: Ages and Stages Questionnaires: Social-Emotional Scale), were assessed at 12-months of age. RESULTS: In ATP, social support was associated with lower offspring problems (pregnancy: ß = -0.15; post-birth: ß = -0.12) and greater competencies (pregnancy: ß = 0.12; post-birth: ß = 0.16) at 12 months. In Triple B, social support also predicted lower offspring problems (pregnancy: ß = -0.11; post-birth: ß = -0.07) and greater competencies (pregnancy: ß = 0.07) at 12 months. Findings did not indicate an association between support at eight-weeks post-birth and subsequent competencies (ß = 0.06). CONCLUSIONS: Evidence suggests that perinatal social support promotes healthy infant social and emotional development. These results underscore the critical importance of social support for mothers transitioning into parenthood.

Improving knowledge of rare disorders since 1993: the Australian Paediatric Surveillance Unit.

The Australian Paediatric Surveillance Unit (APSU), established in 1993 to address the paucity of national data on rare childhood disorders, has become an invaluable research resource. It facilitates prospective, active surveillance for a variety of rare disorders, with monthly reporting by ~1500 paediatricians, who are invited to notify incident cases and provide demographic and clinical data. APSU is highly collaborative (used by >400 individuals/organisations), patient-informed and productive (>300 publications). In 30 years, 72 studies have been initiated on rare infections, and genetic, psychological and neurological disorders, and injuries. Return rates of monthly report cards were >90% for 30 years and paediatricians have provided data for >90% of notified cases. Although there are limitations, including case underascertainment in remote regions, APSU often provides the only available national data. APSU has assisted the government in reporting to the WHO, developing national strategies, informing inquiries and investigating disease outbreaks. APSU data have informed paediatrician education, practice, policy, and service development and delivery. APSU was integral in establishing the International Network of Paediatric Surveillance Units (INoPSU) and supporting development of other units. APSU's expanded remit includes one-off surveys, hospital audits, systematic reviews, studies on the impacts of rare disorders on families, surveillance evaluations, and joint studies with INoPSU members. Paediatricians value the APSU, reporting that APSU data inform their practice. They must be congratulated for an outstanding collective commitment to the APSU, in providing unique data that contribute to our understanding of rare disorders and support optimal, evidence-based care and improved child health outcomes.

The effects of doxapram and its potential interactions with K2P channels in experimental model preparations.

The channels commonly responsible for maintaining cell resting membrane potentials are referred to as K2P (two-P-domain K+ subunit) channels. These K+ ion channels generally remain open but can be modulated by their local environment. These channels are classified based on pharmacology, pH sensitivity, mechanical stretch, and ionic permeability. Little is known about the physiological nature of these K2P channels in invertebrates. Acidic conditions depolarize neurons and muscle fibers, which may be caused by K2P channels given that one subtype can be blocked by acidic conditions. Doxapram is used clinically as a respiratory aid known to block acid-sensitive K2P channels; thus, the effects of doxapram on the muscle fibers and synaptic transmission in larval Drosophila and crawfish were monitored. A dose-dependent response was observed via depolarization of the larval Drosophila muscle and an increase in evoked synaptic transmission, but doxapram blocked the production of action potentials in the crawfish motor neuron and had a minor effect on the resting membrane potential of the crawfish muscle. This indicates that the nerve and muscle tissues in larval Drosophila and crawfish likely express different K2P channel subtypes. Since these organisms serve as physiological models for neurobiology and physiology, it would be of interest to further investigate what types of K2P channel are expressed in these tissues. (212 words).

Ophthalmic Findings in Aboriginal Children with High Rates of Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder: The Lililwan Project.

PURPOSE: To describe ophthalmic findings in an Indigenous paediatric population and the associations between fetal alcohol spectrum disorder (FASD), prenatal alcohol exposure (PAE), and eye anomalies. METHODS: Medical records were reviewed for eye problems, and eye assessments were conducted by an orthoptist or ophthalmologist in the Lililwan Project cohort, which comprised 108 (81%) of all children born between 2002 and 2003, and residing in the remote Fitzroy Valley, Western Australia in 2010. Values from ophthalmic assessments and prevalence of abnormalities were presented for the total cohort and stratified by group: FASD; PAE (no FASD); and No PAE. RESULTS: Of children, 55% had PAE and 19% FASD. Most (98%) had normal vision; 15.6% had keratometry cylinder values indicating astigmatism and potential for improved vision with glasses. Strabismus (22.3%), short palpebral fissure length (PFL; 21.3%), upslanting palpebral fissures (12.0%), follicular trachomatous inflammation (6.9%), abnormal slit lamp assessments (6.7%), retinal tortuosity (6.7%), and blepharoptosis (5.6%) were identified. Strabismus and trachoma rates were higher than in the general child population. Ophthalmic findings were similar between groups except for prevalence of short PFL (FASD > No PAE; p = 0.003); abnormal keratometry cylinder values (FASD [29.4%] and PAE (no FASD) [20.0%] > No PAE [5.3%]; p = 0.031) and blepharoptosis (FASD [9.5%] > other groups [0%]; p = 0.040). CONCLUSION: Despite the small sample, some eye abnormalities were higher in children with PAE and/or FASD. Access to eye services or assessment of vision and structural eye anomalies is essential for Indigenous children, particularly those with PAE or FASD to allow early effective treatment.

Associations between low-moderate prenatal alcohol exposure and brain development in childhood.

BACKGROUND: The effects of low-moderate prenatal alcohol exposure (PAE) on brain development have been infrequently studied. AIM: To compare cortical and white matter structure between children aged 6 to 8 years with low-moderate PAE in trimester 1 only, low-moderate PAE throughout gestation, or no PAE. METHODS: Women reported quantity and frequency of alcohol consumption before and during pregnancy. Magnetic resonance imaging was undertaken for 143 children aged 6 to 8 years with PAE during trimester 1 only (n = 44), PAE throughout gestation (n = 58), and no PAE (n = 41). T1-weighted images were processed using FreeSurfer, obtaining brain volume, area, and thickness of 34 cortical regions per hemisphere. Fibre density (FD), fibre cross-section (FC) and fibre density and cross-section (FDC) metrics were computed for diffusion images. Brain measures were compared between PAE groups adjusted for age and sex, then additionally for intracranial volume. RESULTS: After adjustments, the right caudal anterior cingulate cortex volume (pFDR = 0.045) and area (pFDR = 0.008), and right cingulum tract cross-sectional area (pFWE < 0.05) were smaller in children exposed to alcohol throughout gestation compared with no PAE. CONCLUSION: This study reports a relationship between low-moderate PAE throughout gestation and cingulate cortex and cingulum tract alterations, suggesting a teratogenic vulnerability. Further investigation is warranted.