Scurvy and vitamin C deficiency in an Australian tertiary children's hospital.

AIM: We aimed to investigate the frequency of vitamin C deficiency scurvy in the Australian paediatric context, describe cohorts at risk, and identify factors associated with development of symptoms in children with vitamin C deficiency. We also aimed to propose a management guideline for children with features of scurvy. METHOD: A retrospective study was done at a tertiary paediatric hospital in Australia over a three-year period, from August 2019 to July 2022. Children from birth to 18 years old, whose vitamin C levels were low (<23 µmol/L), were included. Data extracted from hospital medical records included demographics, weight, co-morbidities, eating disorder diagnoses, clinical features, investigations and treatment. Descriptive statistics and risk statistics were performed. RESULTS: In a cohort of 887 patients who had their vitamin C levels checked, we identified 272 (31%) who had a vitamin C level <23 µmol/L. Of these, 13 (5%) were symptomatic of vitamin C deficiency and 19 (7%) may have been symptomatic. In patients with vitamin C deficiency, 248 (91%) had comorbidities, neurodevelopmental disorders being most common, and 176 (65%) had restricted eating. When the asymptomatic and symptomatic groups were compared, in the symptomatic group, there was a significantly lower vitamin C level and disordered eating related to autism spectrum disorders was more common. CONCLUSION: In order to avoid delayed diagnoses and unnecessary investigations, clinicians should be familiar with symptoms of scurvy and perform a dietary assessment, vitamin C assay, and commence empiric vitamin C supplementation where appropriate.

Clinical and diagnostic utility of genomic sequencing for children referred to a Kidney Genomics Clinic with microscopic haematuria.

BACKGROUND: Microscopic haematuria in children is associated with the risk of progression to chronic kidney disease. Genetic disease is an important potential aetiology. Genomic sequencing presents the most effective diagnostic route for these conditions, but access remains inequitable internationally. METHODS: We conducted a retrospective review of the electronic medical records of a Kidney Genomics Clinic (KGC) from January 2016 to December 2021. RESULTS: Sixty patients were referred to the KGC with haematuria over this period. Forty-three percent of patients had analysis of a limited haematuria panel (COL4A1, COL4A3, COL4A4, COL4A5, MYH9) with 58% receiving a genetic diagnosis. Forty-two percent of referred patients had further analysis of genes implicated in the development of kidney disease, and 36% received a diagnosis. Eight percent of patients underwent cascade testing for a known familial variant, and all received a diagnosis. Children with the highest levels of haematuria (> 500 × 106/L red blood cells) had the highest diagnostic yield (67%). Proteinuria, defined as a urinary protein to creatinine ratio > 20, increased the diagnostic yield from 31 to 65%. Importantly, negative genetic analysis can still have significant clinical utility for patients by altering surveillance and further management; the genetic result had clinical utility in 60% of patients. CONCLUSIONS: Our KGC review highlights the substantial clinical utility and diagnostic yield of genomic analysis for microscopic haematuria in paediatric patients. Whilst the management of variants of uncertain significance can be challenging, a multidisciplinary team including genetic counselling can help ensure these patients are followed up meaningfully. A higher resolution version of the Graphical abstract is available as Supplementary information.

Decreased in-hospital mortality rate following implementation of a comprehensive electronic medical record system.

AIM: To evaluate changes in in-hospital mortality rate following implementation of a comprehensive electronic medical record (EMR) system. METHODS: Before and after study of 355,709 hospital discharges, over an 8-year period, at a paediatric teaching hospital. The major outcome measures were crude number of in-hospital deaths, deaths per 1000 discharges, and standardised mortality ratio. RESULTS: Primary analysis of data from 2 years before and 2 years after EMR go-live showed a reduction in absolute mortality of 33 deaths, a reduction in the mortality rate of 0.48 per 1000 discharges (95% CI 0.09, 0.88 per 1000): and a relative 22% decrease (95% CI: 4%, 36%, P = 0.02) in deaths per 1000 discharges from 2.20 to 1.72. There was also a reduction in standardised mortality ratio of 47% (95% CI: 18%, 66%, P = 0.004). Post-hoc analysis of mortality rates for an additional 2-year pre-intervention period indicated that these changes in the mortality rate were not part of a pre-existing downward trend. Further analysis of an additional 20-month post-intervention period suggests that the reduced mortality rate has been sustained. CONCLUSION: We documented evidence of a clinically important decrease in in-hospital mortality rate following the implementation of a modern comprehensive EMR system in an Australian paediatric teaching hospital. The study does not prove a causal relationship, and it is possible that other factors explain some, or all, of this difference, but no changes in the hospital population or other major interventions were identified as alternative explanations for this observed change.

Impact of COVID-19 public health restrictions on hospital admissions for young infants in Victoria, Australia.

AIM: Strict public health measures during the COVID-19 pandemic led to less support for infants and their parents. We aimed to characterise the frequency and nature of infant admissions to the Royal Children's Hospital (RCH), Melbourne in 2020, compared to the previous year. METHODS: A retrospective review of medical records identified infants ≤3 months admitted to the general medicine unit, RCH from March to September in 2019 and 2020. Diagnoses potentially related to the impact of public health measures and reduced family and community supports were identified and compared to all infant diagnoses across both years. Clinical characteristics and need for referral for additional supports or mental health services were also ascertained. RESULTS: There were fewer admissions for infants ≤3 months in 2020 (n = 411) compared to 2019 (n = 678), with a threefold increase in admissions with a primary or secondary diagnosis of feeding difficulties, growth disturbance, infant irritability or maternal mental health concerns (191/411; 46% vs. 97/678; 14%). There were more infants of first-time parents (112/191; 59% vs. 44/97; 45%) and a reduction in the number of admissions due to infection (145/411; 35%; vs. 467/678; 69%). CONCLUSION: During the COVID-19 pandemic, there was a threefold increase in admissions for infants ≤3 months due to poor growth, feeding difficulties, irritability and maternal mental health concerns in 2020 compared to 2019. These findings may inform future pandemic planning and policy development to ensure maintenance of community supports such as maternal child health nurse (MCHN) service delivery for young infants.

Characteristics and outcomes of SARS-CoV-2 infection in Victorian children at a tertiary paediatric hospital.

AIM: Victoria experienced two 'waves' of COVID-19 between March and September 2020 and more cases than any other jurisdiction in Australia. Although world-wide reports of COVID-19 reflect that children are less likely to experience severe disease compared with adults, hospitalisations and deaths have been reported. We report testing and outcomes of children with SARS-CoV-2 infection presenting to a tertiary paediatric hospital in Melbourne. METHODS: We conducted a prospective cohort study at The Royal Children's Hospital (RCH), including all children and adolescents (aged 0-18 years) who presented and were tested for SARS-CoV-2 over a 6-month period, between 21 March 2020, up to the 21 September 2020. Detailed epidemiological and clinical data were recorded. RESULTS: A total of 19 708 tests for SARS-CoV-2 were performed in 14 419 patients. One hundred and eighty patients tested positive for SARS-CoV-2 (1.2%). 110 (61%) were symptomatic, 60 (33%) were asymptomatic and 10 (6%) were pre-symptomatic. Close contacts of a positive case were associated with a higher risk of a testing positive for SARS-CoV-2 (120/2027 (6%) vs. 60/14589 (0.4%), RD 5.5 (95% CI 4.5 to 6.5), P < 0.001). Eighteen (10%) SARS-CoV-2-positive patients were admitted to hospital with one patient requiring intensive care. All patients recovered fully with no deaths. CONCLUSION: In Victorian children presenting to a tertiary hospital, SARS-CoV-2 infection caused predominantly mild or asymptomatic infection, with most children not requiring hospitalisation.

No difference in functional outcomes, quality of life and survivorship between metal-backed and all-polyethylene tibial components in unicompartmental knee arthroplasty: a 10-year follow-up study.

PURPOSE: The purpose of this study was to compare functional outcomes, quality of life and survivorship at a minimum of 10 years postoperatively, between MB and AP tibial components in fixed-bearing UKAs. METHODS: A retrospective cohort study of 146 Query ID="Q3" Text="Author names: Please confirm if the author names are presented accurately and in the correct sequence (Lo Ngai Nung, Yeo Seng Jin). Also, kindly confirm the details in the metadata are correct." UKAs performed between 2004 and 2007 by a single fellowship-trained arthroplasty surgeon was carried out. 27 UKAs received MB tibial components and 119 UKAs received AP tibial components. The cohort was followed up prospectively for 10 years. Functional outcomes were compared using the Knee Society Functional Score (KSFS), Knee Society Knee Score (KSKS) and Oxford Knee Score (OKS). Quality of life measures were obtained from the Physical Component Summary (PCS) and Mental Component Summary (MCS), derived from the Short Form 36 Health Survey (SF-36). Propensity score matching was performed in a 1:3 ratio of MB versus AP tibial components to account for possible confounding variables. Thereafter, outcomes between the two groups were compared. The proportion of patients who had attained the minimum clinically important difference (MCID) for the abovementioned scores was recorded as well. RESULTS: After propensity score matching, there were 28 UKAs with MB tibial components and 76 UKAs with AP tibial components. There was no significant difference between the two groups in functional outcomes (KSFS, KSKS and OKS), quality of life (PCS and MCS) and survivorship (92.3% vs 91.1%, respectively) at a minimum of 10 years postoperatively. However, a significantly higher proportion of patients in the group with AP tibial components attained the MCID for PCS at 10 years postoperatively, compared to those with MB tibial components (p = 0.031). CONCLUSION: In conclusion, there were no significant differences in functional outcomes measures, quality of life and survivorship between MP and AP tibial components at a minimum of 10 years postoperatively. LEVEL OF EVIDENCE: III.

Location of Talar Osteochondral Defects in Chronic Lateral Ankle Instability in an Asian Population.

Osteochondral defect of the talus is traditionally described to involve the anterolateral and posteromedial portion of the talar dome in patients with chronic lateral ankle instability. Recent studies challenged this notion with advances in preoperative imaging and arthroscopy. Since Asian patients are more prone to ligamentous laxity, we postulate that the morphology and severity of osteochondral defects may be different in this population. Intraoperative records of 272 patients undergoing modified Broström-Gould procedure were reviewed for arthroscopic evidence of osteochondral defects. We characterized the morphology according to an anatomical 9-grid classification. Talar osteochondral defects were seen in 52 (19.1%) patients with a double lesion present in 1 patient. Medial-sided lesions account for nearly 3-quarters (n = 38, 73.1%) of all lesions and tend to be larger (79.4 ± 55.7 mm2 vs 51.0 ± 28.6 mm2, p =.08). There was no osteochondral defect seen in the central zones. There was no significant gender or age differences between patients with medial and lateral lesions. The most commonly performed procedure was microfracture. Osteochondral defects are commonly encountered in our Asian patients undergoing surgery for chronic lateral ankle instability. Contrary to published data, medial lesions are prevalent with no central lesions seen.

Nitric therapy in preterm infants: rationalised approach based on functional neonatal echocardiography.

AIM: Use of inhaled nitric oxide (iNO) in preterm infants is not supported by current evidence. In 2013, in Australia and New Zealand, 14% infants' ≤25 weeks of gestations were administered iNO. Within the cohort administered iNO, we aimed to identify subgroups where it may be more efficacious and compared characteristics before and after the set-up of the functional echocardiography (fEcho) programme. METHODS: A retrospective audit for the period 2000-2013 involving preterm infants administered iNO in the first four weeks of life was performed. Comparisons were made between the two time epochs: up to 2007 and post-2007. RESULTS: Eighty-five infants fulfilled the inclusion criteria; 62 (73%) were ≤28 weeks of gestation; 51 (60%) survived. Amongst survivors, gestation and birthweight were higher and oxygenation index (OI) was lower. Fourteen (16.5%) infants weighed small for gestation age; survival was lower in this subgroup (6/14, 43%, p = 0.0005). The fEcho programme increased prenitric assessments for a definitive diagnosis and monitoring; iNO was started earlier, at a lower OI with a trend towards reduced usage (hours). CONCLUSION: Characteristics of subgroups (within the cohort of infants ≤34 weeks of gestation) more likely to benefit from iNO therapy were identified. Use of fEcho could rationalise usage.

Drosophila TDP-43 dysfunction in glia and muscle cells cause cytological and behavioural phenotypes that characterize ALS and FTLD.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that are characterized by cytoplasmic aggregates and nuclear clearance of TAR DNA-binding protein 43 (TDP-43). Studies in Drosophila, zebrafish and mouse demonstrate that the neuronal dysfunction of TDP-43 is causally related to disease formation. However, TDP-43 aggregates are also observed in glia and muscle cells, which are equally affected in ALS and FTLD; yet, it is unclear whether glia- or muscle-specific dysfunction of TDP-43 contributes to pathogenesis. Here, we show that similar to its human homologue, Drosophila TDP-43, Tar DNA-binding protein homologue (TBPH), is expressed in glia and muscle cells. Muscle-specific knockdown of TBPH causes age-related motor abnormalities, whereas muscle-specific gain of function leads to sarcoplasmic aggregates and nuclear TBPH depletion, which is accompanied by behavioural deficits and premature lethality. TBPH dysfunction in glia cells causes age-related motor deficits and premature lethality. In addition, both loss and gain of Drosophila TDP-43 alter mRNA expression levels of the glutamate transporters Excitatory amino acid transporter 1 (EAAT1) and EAAT2. Taken together, our results demonstrate that both loss and gain of TDP-43 function in muscle and glial cells can lead to cytological and behavioural phenotypes in Drosophila that also characterize ALS and FTLD and identify the glutamate transporters EAAT1/2 as potential direct targets of TDP-43 function. These findings suggest that together with neuronal pathology, glial- and muscle-specific TDP-43 dysfunction may directly contribute to the aetiology and progression of TDP-43-related ALS and FTLD.

Palliative care in Australian medical student education.

Greater emphasis needs to be placed on medical student palliative care education within the Australian arena. The development of a comprehensive, relevant and practical educational curriculum in this area during medical school is imperative in order to adequately equip the future junior medical workforce. Further development of a national palliative care curriculum as well as research comparing various teaching methods and curricula should be the priorities in the near future.

Letter to the Editor: A comparison of post-COVID vaccine myocarditis classification using the Brighton Collaboration criteria versus (United States) Centers for Disease Control criteria: an update.

Abstract: (No abstract provided).

Long term follow up and outcomes of Covid-19 vaccine associated myocarditis in Victoria, Australia: A clinical surveillance study.

BACKGROUND: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort. METHODS: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed. RESULTS: 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations. CONCLUSIONS: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data.

How appropriately is blood ordered in a rural hospital?

BACKGROUND: Blood products are a limited resource particularly in a rural setting and their appropriate use is important to maintain patient safety and minimise costs. OBJECTIVE: To assess the appropriateness of transfusion practices in a rural hospital. DESIGN/DATA SOURCES: A retrospective medical record audit of packed red blood cell (PRBC) use. SETTING: A rural hospital 300 km northwest of Melbourne. PARTICIPANTS: All patients in Wimmera Base Hospital who had a PRBC crossmatch request from October 2010 to March 2011 inclusive. MAIN OUTCOME MEASURES: Proportion of appropriate transfusions and crossmatch to transfusion ratios. RESULTS: A total of 257 patients and 657 PRBC units were cross-matched during the study period. Of these patients, 28.4% had pre-procedure (elective) cross-matches. Of the elective cross-matches, 27.4% were inappropriate, compared with 16.1% of emergency cross-matches. The cross-match to transfusion ratio (C:T) was 1.59 for emergency requests and 5.96 for elective requests. The C:T ratio was high in the surgical and obstetrics and gynaecology departments. 16.3% of all transfusions were single-unit transfusions. CONCLUSIONS: Emergency requests were predominantly appropriate but a significant proportion of elective requests were inappropriate, suggesting changes in elective crossmatch request protocols, and increased education regarding ordering blood in a rural setting.

Histologically atypical case of Gaucher disease type 1.

This report presents a case of childhood Gaucher disease type 1, a rare inherited metabolic disorder. Although the clinical symptoms were classical, the histological findings in this case were atypical and initially led to diagnostic uncertainty. The pathognomonic histological finding on bone marrow is Gaucher cells, which are lipid-engorged phagocytes secondary to the accumulation of glucosylceramide. These cells typically demonstrate diffuse and avid iron staining using a Prussian blue iron stain. In this case, although the histiocytes seen on bone marrow were abnormal, the absence of iron staining on bone marrow led to a large range of other diagnoses being considered. In retrospect, this anomaly was likely in the setting of prolonged iron deficiency and anaemia as a result of the insidious nature of this presentation. The prognosis of type 1 Gaucher disease is favourable, with current treatments significantly improving duration and quality of life. We explore the utility of a collaborative multidisciplinary approach in addressing diagnostic uncertainty and the importance in making a diagnosis for Gaucher disease type 1 in order to provide appropriate and targeted treatment.

Correcting Hypernatremia in Children.

BACKGROUND: In children with hypernatremia, current clinical guidelines recommend a reduction in serum sodium of 0.5 mmol/L per hour or less to avoid complications of cerebral edema. However, no large-scale studies have been conducted in the pediatric setting to inform this recommendation. Therefore, this study aimed to report the association between the rate of correction of hypernatremia, neurological outcomes, and all-cause mortality in children. METHODS: A retrospective cohort study was conducted from 2016 to 2019 at a quaternary pediatric center in Melbourne, Victoria, Australia. All children with at least one serum sodium level ≥150 mmol/L were identified through interrogation of the hospital's electronic medical record. Medical notes, neuroimaging reports, and electroencephalogram results were reviewed for evidence of seizures and/or cerebral edema. The peak serum sodium level was identified and correction rates over the first 24 hours and overall were calculated. Unadjusted and multivariable analyses were used to examine the association between the rate of sodium correction and neurological complications, the requirement for neurological investigation, and death. RESULTS: There were 402 episodes of hypernatremia among 358 children over the 3-year study period. Of these, 179 were community-acquired and 223 developed during admission. A total of 28 patients (7%) died during admission. Mortality was higher in children with hospital-acquired hypernatremia, as was the frequency of intensive care unit admission and hospital length of stay. Rapid correction (>0.5 mmol/L per hour) occurred in 200 children and was not associated with greater neurological investigation or mortality. Length of stay was longer in children who received slow correction (<0.5 mmol/L per hour). CONCLUSIONS: Our study did not find any evidence that rapid sodium correction was associated with greater neurological investigation, cerebral edema, seizures, or mortality; however, slow correction was associated with a longer hospital length of stay.

Analyzing an immunization resource website: User browsing trends.

PURPOSE: Access to internet-based resources may help to improve population health awareness and literacy surrounding immunization related topics. The primary aim of this study was to evaluate and analyze trends for a single immunization resource website, the Melbourne Vaccine Education Centre (MVEC). PRINCIPAL RESULTS: Over a four-year period from 2019 to 2022, the website had over 2 million visitors from 236 countries. Users were predominantly female, in the 25 to 44 year age bracket and accessed resources using a mobile device. There was significant interest in specific vaccine related topics, particularly during the COVID-19 pandemic, that corresponded with key vaccine related recommendations and updates from a national level. Usage patterns saw spikes in interest around topics including COVID-19 vaccine administration techniques and adverse events following immunization. MAJOR CONCLUSIONS: Use of online platforms including websites such as MVEC may reflect trends and behaviors towards immunization related information. Analysis of usage patterns have provided user insights into key domains of interest including areas such as vaccine administration, policies and programs, vaccine safety and barriers to vaccine uptake.