Getting to the heart of the matter-are two agents really better than one for the treatment of staphylococcal infective endocarditis?

The recently published European Society of Cardiology guidelines for infective endocarditis management recommends daptomycin combination therapy for the treatment of staphylococcal endocarditis in severe penicillin allergy, rather than daptomycin monotherapy. We discuss the evidence base behind this recommendation, highlighting concerns regarding the lack of robust clinical studies, increased cost and logistical considerations, and adverse effects of combination therapy. Although further studies are required to elucidate the role of combination vs monotherapy in these patients, we propose a pragmatic management approach to reduce the risk of adverse antimicrobial side effects and limit costs, while aiming to maintain treatment efficacy.

Utilising in situ simulation within translational simulation programmes to evaluate and improve multidisciplinary response to anaphylaxis in the paediatric emergency department.

OBJECTIVE: The prevalence of paediatric anaphylaxis is rising in Australia. Treatment requires timely administration of intramuscular (IM) adrenaline. Study goals included utilising in situ simulation (ISS) within a translational simulation (TS) programme as a diagnostic tool to identify the frequency and cause of IM adrenaline errors in a paediatric ED, and utilising ISS to evaluate multidisciplinary emergency team response to anaphylaxis. METHODS: A prospective observational study was conducted in the Royal Children's Hospital Melbourne ED utilising an ISS anaphylaxis scenario with a debrief pro forma within an established ISS/TS programme. RESULTS: Twenty-three anaphylaxis ISS were delivered over 16 months. One hundred and sixty-four multidisciplinary staff participated (mean of 8 per session). Median times (in minutes) for the total ISS were 12:33 (interquartile range [IQR] 9:06-15:19), consisting of the scenario 4:07 (IQR 3:33-4:44) and debriefing 9:00 (IQR 5-11). IM adrenaline was administered in all ISS within 5 min, median 2:57 (IQR 2:30-3:40). Adrenaline medication errors occurred in 30% ISS (7/23). Errors included three (13%) administrations and four (17%) potential or 'near misses' associated with a verbal order or medication preparation error. A weight-based medication cognitive aid was utilised in 56% (13/23) ISS but was not utilised in all three administration errors. CONCLUSIONS: ISS within TS programmes was successfully utilised as a diagnostic tool in identifying that medication errors were common during anaphylaxis management in the ED. Improving access to adrenaline in dosing boxes and promoting the utilisation of weight-based cognitive aids alongside ISS education will likely reduce errors and improve patient safety.

Mid-Arm Point in PAEDiatrics (MAPPAED): An effective procedural aid for safe pleural decompression in trauma.

OBJECTIVE: Life-threatening thoracic trauma requires emergency pleural decompression and thoracostomy and chest drain insertion are core trauma procedures. Reliably determining a safe site for pleural decompression in children can be challenging. We assessed whether the Mid-Arm Point (MAP) technique, a procedural aid proposed for use with injured adults, would also identify a safe site for pleural decompression in children. METHODS: Children (0-18 years) attending four EDs were prospectively recruited. The MAP technique was performed, and chest wall skin marked bilaterally at the level of the MAP; no pleural decompression was performed. Radio-opaque markers were placed over the MAP-determined skin marks and corresponding intercostal space (ICS) reported using chest X-ray. RESULTS: A total of 392 children participated, and 712 markers sited using the MAP technique were analysed. Eighty-three percentage of markers were sited within the 'safe zone' for pleural decompression (4th to 6th ICSs). When sited outside the 'safe zone', MAP-determined markers were typically too caudal. However, if the site for pleural decompression was transposed one ICS cranially in children ≥4 years, the MAP technique performance improved significantly with 91% within the 'safe zone'. CONCLUSIONS: The MAP technique reliably determines a safe site for pleural decompression in children, albeit with an age-based adjustment, the Mid-Arm Point in PAEDiatrics (MAPPAED) rule: 'in children aged ≥4 years, use the MAP and go up one ICS to hit the safe zone. In children <4 years, use the MAP.' When together with this rule, the MAP technique will identify a site within the 'safe zone' in 9 out of 10 children.

No advantage with navigated versus conventional mechanically aligned total knee arthroplasty-10 year results of a randomised controlled trial.

PURPOSE: Computer-assisted surgery (CAS) total knee arthroplasty (TKA) remains a controversial area of surgical practice. The aim of this study is to report the ten-year revision rates and patient-reported outcome measures (PROMS) of a single-blinded, prospective, randomised controlled trial comparing electromagnetically (EM) navigated and conventional TKA. METHODS: 199 patients were randomised to receive either EM navigated or conventional TKA where the aim of implantation was neutral mechanical alignment in all cases. Ten-year revision rates were collated and compared between the two intervention groups. Longitudinal PROMS data was collected prospectively at various time points up to 10 years post-operatively. RESULTS: Over the ten-year period, there were 23 deaths (22.8%) in the EM navigation cohort and 30 deaths (30.6%) in the conventional cohort. At 10 years post-operatively, there was no statistically significant difference in all cause revision between the EM navigation and conventional cohort (4.0 vs 6.1%, p = 0.429). When analysing causes of revision that might be influenced by utilising EM navigation, there was no statistically significant difference in revisions (3.0% EM navigated vs 4.1% conventional group, p = 0.591). Patients that received navigated TKAs had improved Oxford Knee Society, American Knee Society Score and range of motion at 3 months following surgery compared to conventional TKA (p = 0.002, p = 0.032, and p = 0.05, respectively). However, from 1 to 10 years post-operatively, both interventions had equivalent outcomes. CONCLUSION: There is no difference in revision rates or clinical outcomes comparing EM navigated versus conventional TKA at ten-year follow-up. The expected mortality rate makes it unlikely that a difference in revision rates will reach statistical significance in the future. In the setting of an experienced knee arthroplasty surgeon, it is difficult to justify the additional costs of CAS in TKA surgery. LEVEL OF EVIDENCE: I.

Increased paediatric emergency mental health and suicidality presentations during COVID-19 stay at home restrictions.

OBJECTIVE: Anecdotal reports indicate an increase in mental health presentations and acuity to EDs during the COVID-19 pandemic and associated stay at home restrictions. Paediatric and adolescent data to confirm this are unavailable in the Australian setting. METHODS: Retrospective electronic medical record review of all ED patients with mental health discharge codes at a large tertiary children's hospital in Australia during the period of stay at home restrictions from 1 April to 30 September 2020 compared with the same dates in 2019. RESULTS: We found a 40% decrease in ED presentations (18 935-11 235) with a concurrent 47% increase in mental health presentations (809-1190) to ED during the study periods between 2019 and 2020. This resulted in an increase of 100 mental health admissions from ED. Diagnoses with greatest percentage increases were eating disorders, social issues and suicidality. We found suicidality presentation numbers were highest in June to September 2020 compared with 2019. Patients with a diagnosis of suicidality had a higher rate of re-presentation in 2020 (1.83 presentations per patient) compared to 2019 (1.38 presentations per patient). CONCLUSIONS: Despite an overall decrease in ED presentations, the absolute increase in mental health presentations for children and adolescents during the stay at home restriction period was pronounced. It is unclear how sustained this change and the impact on mental health resource use will be post-pandemic.

Electromagnetic Navigated Versus Conventional Total Knee Arthroplasty-A Five-Year Follow-Up of a Single-Blind Randomized Control Trial.

BACKGROUND: The objective of this study is to provide the 5-year follow-up results of a randomized study comparing conventional versus electromagnetic computer navigated total knee arthroplasty. METHODS: Analysis of 127 patients (66 navigated and 61 conventional surgeries) was performed from a prospective, single-blinded, randomized controlled trial. Patient-reported outcome measures were collected at 5 years after surgery and compared with previously published 1-year clinical outcomes. Five-year surgical revision rates were collated and compared between intervention groups. RESULTS: Overall, there have been continued improvements in the clinical scores of patients in both groups when compared with clinical data at 1 year; however, at 5 years, there is no statistical difference in any of the patient-reported outcome measures between conventional and navigated surgery. Interestingly, improved implant survivorship was observed in the navigated (0% revision rate) compared with the conventional group (4.9% all-cause revision rate). CONCLUSION: Electromagnetic computer navigated technology produces similar clinical outcomes compared with traditional surgery. Further work is required to monitor implant survivorship, and clinical outcomes with long-term follow-up, to determine the cost effectiveness of this technology.

Risk factors for carriage of meningococcus in third-level students in Ireland: an unsupervised machine learning approach.

The aim of this study was to examine the risk factors for pharyngeal carriage of meningococci in third-level students using an unsupervised machine learning approach. Data were gathered as part of meningococcal prevalence studies conducted by the Irish Meningitis and Sepsis Reference Laboratory (IMSRL). Pharyngeal swab cultures for meningococcal carriage were taken from each student once they had completed a single-page anonymous questionnaire addressing basic demographics, social behaviors, living arrangements, vaccination, and antibiotic history. Data were analyzed using multiple correspondence analysis through a machine learning approach.In total, 16,285 students who had a pharyngeal throat swab taken returned a fully completed questionnaire. Overall, meningococcal carriage rate was 20.6%, and the carriage of MenW was 1.9% (n = 323). Young Irish adults aged under 20 years and immunized with the meningococcal C vaccine had a higher MenW colonization rate (n = 171/1260, 13.5%) compared with non-Irish adults aged 20 years or older without the MenC vaccine (n = 5/81, 6%, chi-square = 3.6, p = .05). Unsupervised machine learning provides a useful technique to explore meningococcal carriage risk factors. The issue is very complex, and asked risk factors only explain a small proportion of the carriage. This technique could be used on other conditions to explore reasons for carriage.

Emergency mental health presentations in children with autism spectrum disorder and attention deficit hyperactivity disorder.

AIM: To characterise the key features and management of young people presenting to the emergency department (ED) with a mental health (MH) complaint and a known diagnosis of autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD). METHODS: Retrospective review of all ED MH presentations in children aged 7-17 years, presenting over a 12-month period from the 1st of January 2018 to the 31st of December 2018, to the Royal Children's Hospital in Melbourne, Australia. Univariate analyses were carried out to examine the relationship between an underlying diagnosis of ASD and/or ADHD and a number of key presentation variables. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for ED management outcomes. RESULTS: There were 374 presentations in this cohort, representing 28% of the total MH presentations in 2018. The most common reason for presentation was acute severe behavioural disturbance. Young people with ASD and ADHD were at increased risk of having an acute crisis team response activated (ASD RR 2.3, CI 1.6-3.3, ADHD RR 2.2, CI 1.2-4.1). Compared to those without either diagnosis, young people with ASD were more likely to be physically restrained (RR 2.8, CI 1.7-4.6), managed in seclusion (RR 3.3, CI 1.7-6.4) and to receive medication to assist with behavioural de-escalation (RR 2.8, CI 1.6-4.9). CONCLUSIONS: Children with ASD and/or ADHD represent one-quarter of all children presenting to the ED with MH complaints. They experience high rates of acute severe behavioural disturbance. Future research is needed to co-design, implement and evaluate better approaches for their management.

Mental health presentations to the paediatric emergency department: A retrospective study.

AIM: To describe a cohort of patients aged 7-17 years presenting with mental health (MH) problems to an Australian tertiary paediatric emergency department (ED), in order to identify: (i) predictors of admission; and (ii) prolonged length of stay (LOS); (iii) reasons for ED presentation based on diagnosis and (iv) differences between major diagnostic groups. METHODS: Data for all presentations from 1 January 2018 to 31 December 2018 were extracted and analysed from the hospital's electronic medical record system. MH presentations were identified though rule-based coding and manual file review. RESULTS: In this 12-month period, 1071 children had 1690 emergency MH presentations constituting 6.7% of all ED presentations for children aged 7-17 years. Collectively, the leading cause for presentations was suicidal ideation, self-harm or drug overdose (55%). Compared to discharged patients, admitted patients were more likely to be female (odds ratio (OR) 1.82, confidence interval (CI) 1.41-2.35), aged over 14-years (OR 2.50, CI 1.98-3.15), triaged with high acuity (OR 2.70, CI 2.00-3.65) and arrive by ambulance or police (OR 1.31, CI 1.04-1.64). The highest risk diagnosis associated with admission was eating disorders (OR 9.19, CI 5.48-15.40). Patients with a prolonged LOS (>8 h) were more likely to need admission (OR 5.38, CI 3.81-7.61) and be diagnosed with drug overdose (OR 2.39, CI 1.51-3.80) or acute behavioural disturbance (OR 1.61, CI 1.09-2.39). CONCLUSION: Mental health presentations constitute a large proportion of ED presentations. Suicidal behaviour and self-harm account for half of them. We have identified patients at increased risk of admission and prolonged ED LOS.

Psychotropic medication use for paediatric mental health patients in an emergency department.

OBJECTIVE: There is paucity of evidence for psychotropic medication use in children and adolescents presenting with mental health (MH) problems to the ED. We set out to describe paediatric psychotropic medication use in the ED. METHODS: We conducted a retrospective electronic medical record review of ED patients with MH discharge codes at a tertiary paediatric ED in 2018. We assessed the epidemiology and management of patients who received a psychotropic medication. We calculated the odds ratios (ORs with 95% confidence intervals [CIs]) of key demographic factors of medicated versus non-medicated MH patients. RESULTS: During 2018 there were 1695 MH-related presentations to the ED. Of these, 280 presentations resulted in the patient receiving a psychotropic medication (16.5%). Medicated children with MH illness were more likely to be male (OR 1.50, 95% CI 1.16-1.96), have a more acute triage category (OR 3.37, 95% CI 2.28-4.98), have an ED length of stay greater than 12 h (OR 3.96, 95% CI 2.56-6.13) and present after hours (OR 1.51, 95% CI 1.16-1.96). Most had a diagnosis of acute behavioural disturbance or suicidal ideation. A variety of treatment regimens were used but children primarily received a single oral agent (diazepam or olanzapine). Parenteral medications were given in 8.6%. No adverse events were recorded. CONCLUSION: A minority of children with MH presentations to the ED were medicated. It will require multicentre research to determine the most effective and safe acute psychotropic agents for oral and parenteral use in children in the ED.

The utility of ketones at triage: a prospective cohort study.

OBJECTIVE: To establish the relationship between serum point-of-care (POC) ketones at triage and moderate-to-severe dehydration based on the validated Gorelick Scales. DESIGN, SETTING AND PATIENTS: Prospective unblinded study from April 2016 to February 2017 in a paediatric emergency department. Patients aged 1 month to 5 years, with vomiting and/or diarrhoea and/or decreased intake with signs of moderate or severe dehydration or clinical concern for hypoglycaemia were eligible. MAIN OUTCOME MEASURES: The primary outcome was to describe the relationship between triage POC ketones to the two Gorelick Scales. Secondary outcomes were to examine the response of ketone levels to fluid/glucose administration and patient disposition. RESULTS: One-hundred and ninety-eight patients were included; median age 1.8 years. The median triage ketones were 4.6 (IQR 2.8-5.6) mmol/L. A weak correlation was identified between triage ketones and the 10-point Gorelick Scale (Spearman's ρ=0.217, p=0.002), however no correlation between triage ketones and the 4-point Gorelick Scale was identified. Those admitted had median triage ketones of 5.2 (IQR 4-6) mmol/L and repeat ketones of 4.6 (IQR 3.3-5.7) mmol/L compared with 4.2 (IQR 2.4-5.3) mmol/L and 2.9 (IQR 1.6-4.2) mmol/L in those discharged home. CONCLUSION: No correlation between triage POC ketones and the 4-point Gorelick Scale was established. POC ketones at triage have poor accuracy for predicting hospital admission. The elevated profile of POC ketones in non-diabetic children with acute illness suggests a potential target of tailored treatments for further research.

The importance of cycle threshold values in interpreting molecular tests for SARS-CoV-2.

Using the Allplex™ 2019-nCoV assay (Seegene, South Korea), 285 samples were tested; 49 (17%) were positive for 3 genes, 4 (1.4%) samples were positive for 2 genes (all N gene and RdRP gene), 8 (3%) samples were positive for 1 gene (all N gene only), and 224 (78.5%) samples were negative.

Children and adolescents with severe acute behavioural disturbance in the emergency department.

OBJECTIVE: Mental health (MH) presentations to ED are increasing in children and adolescents. Little is known about patients with severe acute behavioural disturbance (ABD). We set out to describe patients with ABD severe enough to trigger an acute crisis team response in ED (termed 'Code Grey') and how they differ from other MH patients. METHODS: Retrospective electronic medical record review of all ED patients with MH discharge codes at a tertiary children's hospital. We assessed the epidemiology and management of patients who triggered acute crisis team interventions (Code Grey) as proxy for severe ABD. We calculated the odds ratios (ORs with 95% confidence intervals) of key demographic factors compared to other MH patients. RESULTS: During 2018, there were 85 347 ED presentations of which 1695 (2.0%) were related to MH diagnoses; 84 MH patients had 141 MH presentations triggering 204 Code Greys (26 patients triggered 59% of Code Greys). These patients had higher triage acuity (OR 12.6 [8.3-19.0]), stayed longer in ED (>12 h OR 8.2 [5.1-13.1]) and were more likely to be admitted (OR 2.0 [1.4-3.0]) compared with non-Code Grey MH presentations. Patients were physically (19.2%), mechanically (31.9%) or chemically restrained (37.6%). Eight different medication approaches were used as either a single agent or a combination of oral and/or intramuscular agents. CONCLUSIONS: Children and adolescents with severe ABD differ from other MH presentations and often require physical or chemical restraint. Anticipatory management plans may be valuable for repeat presenters.

Repeated presentation of children and adolescents to the emergency department following self-harm: A retrospective audit of hospital data.

OBJECTIVE: To examine re-presentation rates for self-harm in patients aged 0-18 years to the ED of a tertiary paediatric hospital in Melbourne, Australia, and associated patient, family and hospital presentation factors. METHODS: Data for presentations from 1 July 2016 to 31 December 2018 were extracted from the hospital's electronic medical record system. Self-harm presentations were identified through automated, rule-based coding and manual review of medical notes. Re-presentation rates for intervals up to 12 months were estimated using survival methods with risk factor associations examined using Cox regression. RESULTS: Of the 952 presentations for self-harm after 1 January 2017, 529 were considered first presentations. An estimated 15% (95% confidence interval [CI] 12-19), 20% (95% CI 17-24) and 23% (95% CI 19-27) re-presented for self-harm within 3, 6 and 12 months, respectively. A total of 82% of all presentations were for girls. Patients were more likely to re-present if they had previously presented more than once, were flagged as vulnerable (hazard ratio [HR] 1.35, 95% CI 1.08-1.68), had a history of substance abuse (HR 1.30, 95% CI 1.03-1.64), were female (HR 1.43, 95% CI 0.92-2.21), had self-cut (HR 1.38, 95% CI 0.96-1.97), had an aggressive behaviour response team called during the visit (HR 1.44, 95% CI 0.85-2.45) or had a history of depression (HR 1.27, 95% CI 0.99-1.63). CONCLUSIONS: In this paediatric ED, almost one in four patients re-presented with self-harm within 12 months. Previous presentations and other factors were associated with risk of re-presenting, although no factor was strongly predictive. Future research might examine the generalisability of these findings across settings and explore strategies for prevention.

Delphi assessment of audit and research priorities in an emergency department.

OBJECTIVE: Audit and research projects in the ED are important to improve patient care but can be time and resource consuming. We identified and prioritised audit and research topics among multidisciplinary ED staff to fill perceived knowledge gaps, encourage engagement, reduce duplication and facilitate translation of evidence into clinical practice. METHODS: A two-stage electronic Delphi survey process was undertaken by senior medical, nursing, education and social work staff at the Royal Children's Hospital, Victoria. Survey 1 collected demographic data and audit and research ideas following a series of open-ended questions. Priority themes were defined as those that had more than four responses. Survey 2 used a 7-point Likert ranking of these themes to generate a departmental audit and research prioritisation list. RESULTS: 72/89 (82%) available senior staff responded to survey 1 and 63/83 (76%) responded to survey 2. Survey 1 yielded 208 audit and 130 research topics. Survey 2 established a prioritised list of 17 audit and 14 research topics. Top audit themes were mental healthcare, patient flow, management of sepsis and delays in ED specialist referrals. Top research priorities were the management of sepsis, mental healthcare, management of patients with autism and the management of severe asthma. CONCLUSIONS: This Delphi study has provided departmental audit and research priorities that are perceived to be of importance across the multidisciplinary ED team. This methodology allows strategic allocation of limited resources and may increase staff engagement.

Zinc and vitamin A deficiency in a cohort of children with autism spectrum disorder.

BACKGROUND AND OBJECTIVES: Studies suggest that trace element and vitamin deficiencies are common in children with autism spectrum disorder (ASD). Data describing the rates of vitamin and trace element deficiencies in the ASD population of the northwest of Ireland is lacking. We wished to determine the prevalence of zinc and vitamin A deficiency in the ASD population compared with controls within this geographical area. METHODS: Parents of children aged 2-18 years with ASD were invited to participate in the study. The control group consisted of well children attending the paediatric department for routine blood sampling. Children on vitamin supplements were excluded from both ASD and control groups. Informed written consent was obtained prior to recruitment. Samples were analysed for zinc and vitamin A levels according to standardized laboratory procedures. RESULTS: Seventy-four of the 150 children with ASD who were invited and 72 controls underwent blood sampling. Mean zinc and vitamin A levels were normal in both groups. There were significantly more males in the ASD group (88% versus 56%, p value < 0.001). The mean (SD) zinc level was not different between the groups (ASD 11.7 [1.7] versus control 11.6 [2.1] µmol/L, p value = 0.86). The mean (standard deviation) vitamin A level was higher in the ASD group (ASD 350.6 [82.6] versus 319.2 [82.8] µg/L, p value = 0.03), but this was likely confounded by age. CONCLUSION: Children with ASD in the northwest of Ireland have mean zinc and vitamin A levels within the normal range. It is important that these findings are relayed to health professionals and to parents of children with ASD so that informed decisions on vitamin supplementation can be made.

AraC-Type Regulator Rbf Controls the Staphylococcus epidermidis Biofilm Phenotype by Negatively Regulating the icaADBC Repressor SarR.

Regulation of icaADBC-encoded polysaccharide intercellular adhesin (PIA)/poly-N-acetylglucosasmine (PNAG) production in staphylococci plays an important role in biofilm-associated medical-device-related infections. Here, we report that the AraC-type transcriptional regulator Rbf activates icaADBC operon transcription and PIA production in Staphylococcus epidermidis Purified recombinant Rbf did not bind to the ica operon promoter region in electrophoretic mobility shift assays (EMSAs), indicating that Rbf regulates ica transcription indirectly. To identify the putative transcription factor(s) involved in Rbf-mediated icaADBC regulation, the ability of recombinant Rbf to interact with the promoter sequences of known icaADBC regulators was investigated. Recombinant Rbf bound to the sarR promoter and not the sarX, sarA, sarZ, spx, and srrA promoters. Reverse transcription (RT)-PCR demonstrated that Rbf acts as a repressor of sarR transcription. PIA expression and biofilm production were restored to wild-type levels in an rbf sarR double mutant grown in brain heart infusion (BHI) medium supplemented with NaCl, which is known to activate the ica locus, but not in BHI medium alone. RT-PCR further demonstrated that although Rbf does not bind the sarX promoter, it nevertheless exerted a negative effect on sarX expression. Apparently, direct downregulation of the SarR repressor by Rbf has a dominant effect over indirect repression of the SarX activator by Rbf in the control of S. epidermidis PIA production and biofilm formation. IMPORTANCE: The importance of Staphylococcus epidermidis as an opportunistic pathogen in hospital patients with implanted medical devices derives largely from its capacity to form biofilm. Expression of the icaADBC-encoded extracellular polysaccharide is the predominant biofilm mechanism in S. epidermidis clinical isolates and is tightly regulated. Here, we report that the transcriptional regulator Rbf promotes icaADBC expression by negatively regulating expression of sarR, which encodes an ica operon repressor. Furthermore, Rbf indirectly represses the ica operon activator, SarX. The data reveal complicated interplay between Rbf and two Sar family proteins in fine-tuning regulation of the biofilm phenotype and indicate that in the hierarchy of biofilm regulators, IcaR is dominant over the Rbf-SarR-SarX axis.