Cilostazol attenuates mirabegron-induced hepatic and renal toxicity in rats: regulation of metabolic, oxidative, and inflammatory pathways.

BACKGROUND: Mirabegron (MIRG) is a type of ß3 adrenoceptor agonist that is considered an alternative therapy for the treatment of overactive bladder (OAB) symptoms. Cilostazol (CITZ) is a selective inhibitor of phosphodiesterase (III) that has various pharmacological effects. OBJECTVE: The current study aimed to highlight the regulatory effects of CITZ on MIRG-induced toxicity. MATERIALS AND METHODS: Male rats were divided into six groups. Blood samples were collected to determine different hepatic and kidney function levels along with serum protein electrophoresis and inflammatory factor levels. Histopathological studies and oxidative stress (OS) were also assessed. Kidney and hepatic damage were detected following the administration of MIRG, especially at high doses, due to elevated OS, inflammation, and apoptotic marker levels. RESULTS: Rats receiving CITZ exhibited significant improvements in both hepatic and kidney functions, with decreased inflammation and OS. CONCLUSION: CITZ administration plays a beneficial role in alleviating hepatic and nephrotoxicity induced by MIRG by inhibiting OS and inflammation.

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.

Defining complicated urinary tract infection and route of antibiotics in children presenting to the emergency department: a cohort study using the Melbourne RUPERT clinical score.

OBJECTIVES: Most children with uncomplicated urinary tract infections (UTI) can be managed with oral antibiotics. However, identifying those likely to fail oral and need intravenous antibiotics due to complicating features at presentation is challenging. We aimed to derive, validate and test a score to guide initial antibiotic route. DESIGN: This cohort study enrolled children both prospectively and retrospectively. Patients were divided into two groups based on whether they received intravenous or oral antibiotics after 24 hours, including those who switched between routes. Children diagnosed with confirmed UTI were used to derive then validate the score, comparing complicating clinical features between the two groups. Combinations of significantly differentiating features generated receiver operating characteristic curves and the optimal cut-off for intravenous antibiotic use was selected. SETTING: The emergency department of a tertiary paediatric hospital. PARTICIPANTS: All children aged 3 months-17 years with suspected UTI were eligible, and were included if they fulfilled the diagnostic criteria for UTI. OUTCOME MEASURES: The effectiveness of the derived clinical score to differentiate patients at presentation who had complicated UTI requiring ongoing intravenous antibiotics. RESULTS: There were 1240 patients, of whom 167 children aged 12 months-11 years with confirmed UTI comprised the derivation cohort. The combination of features that performed optimally (area under curve 0.85, 95% CI 0.79 to 0.91) were: rigors, urological abnormality, fever (≥38°C), emesis, recurrent (≥3) UTI, tachycardia: the RUPERT score (1 point each, maximum 6). A score ≥3 accurately classified route of antibiotics after 24 hours for 80% patients (sensitivity 77%, specificity 81%). For the 168 patients in the validation cohort, the score accurately classified 76% (sensitivity 67%, specificity 78%). The score tested well in 'probable' UTI and adolescents, and less well in infants. CONCLUSION: The Melbourne RUPERT score provides the first standardised, easy-to-use score to aid clinicians in deciding route of antibiotics for more complicated UTI in children. It now needs prospective validation.

The characteristics of SARS-CoV-2-positive children in Australian hospitals: a PREDICT network study.

OBJECTIVES: To examine the clinical characteristics and short term outcomes for children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who presented to Australian hospitals during 2020 and 2021. DESIGN, SETTING: Retrospective case review study in nineteen hospitals of the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network from all Australian states and territories, including seven major paediatric tertiary centres and eight Victorian hospitals. PARTICIPANTS: SARS-CoV-2-positive people under 18 years of age who attended emergency departments or were admitted to hospital during 1 February 2020 - 31 December 2021. MAIN OUTCOME MEASURES: Epidemiological and clinical characteristics, by hospital care type (emergency department [ED] or inpatient care). RESULTS: A total of 1193 SARS-CoV-2-positive children and adolescents (527 girls, 44%) attended the participating hospitals (107 in 2020, 1086 in 2021). Their median age was 3.8 years (interquartile range [IQR], 0.8-11.4 years); 63 were Aboriginal or Torres Strait Islander people (5%). Other medical conditions were recorded for 293 children (25%), including asthma (86, 7%) and premature birth (68, 6%). Medical interventions were not required during 795 of 1181 ED presentations (67%); children were discharged directly home in 764 cases (65%) and admitted to hospital in 282 (24%; sixteen to intensive care units). The 384 admissions to hospital (including 102 direct admissions) of 341 children (25 infants under one month of age) included 23 to intensive care (6%); the median length of stay was three days (IQR, 1-9 days). Medical interventions were not required during 261 admissions (68%); 44 children received respiratory support (11%) and 21 COVID-19-specific treatments, including antiviral and biologic agents (5%). Being under three months of age (v one year to less than six years: odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7-4.0) and pre-existing medical conditions (OR, 2.5; 95% CI, 1.9-3.2) were the major predictors of hospital admission. Two children died, including one without a known pre-existing medical condition. CONCLUSION: During 2020 and 2021, most SARS-CoV-2-positive children and adolescents who presented to participating hospitals could be managed as outpatients. Outcomes were generally good, including for those admitted to hospital.

Hospital bed replacement for acute care of children at home during the COVID-19 pandemic through a Hospital-in-the-Home programme.

OBJECTIVES: During the COVID-19 pandemic, we expanded our Hospital-in-the-Home (HITH) programme to increase capacity and manage COVID-19-positive children. We aimed to assess impact on overall HITH activity and COVID-19-positive outcomes. DESIGN: Prospective comparative cohort study. SETTING: The largest paediatric HITH in Australasia, at The Royal Children's Hospital Melbourne. PATIENTS: Children 0-18 years admitted to HITH during the pandemic. INTERVENTION: We developed a COVID-19 responsive service, and a guideline for COVID-19-positive patients. We compared overall activity prior to and during the pandemic, and COVID-19-positive admissions with different variants. MAIN OUTCOMES: We compared outcomes for all HITH patients before and during the pandemic, and for COVID-19-positive patients admitted first to hospital versus directly to HITH. RESULTS: HITH managed 7319 patients from March 2020 to March 2022, a 21% increase to previously, with a 132% telehealth increase. 421 COVID-19-positive patients (3 days-18.9 years) were admitted to HITH, predominantly high risk (63%) or moderately unwell (33%). Rates of childhood infection in Victoria, with proportion admitted to HITH were: original/alpha variant-3/100 000/month, 0.7%; delta-92/100 000/month, 0.8%; omicron-593/100 000/month, 0.3%. Eligible parents of only 29 of 71 (41%) high-risk children were vaccinated. COVID-19-positive children admitted directly to HITH were less likely to receive COVID-19-specific treatment than those admitted to hospital first (14 of 113 (12%) vs 33 of 46 (72%), p<0.001), reflecting more severe respiratory, but not other features in inpatients. 15 of 159 (10%) were readmitted to hospital, but none deteriorated rapidly. CONCLUSIONS: COVID-19-positive children at high risk or with moderate symptoms can be managed safely via HITH at home, the ideal place for children during the pandemic.

Outpatient parenteral antimicrobial therapy: how young is too young?

OBJECTIVE: To report the use, and assess the efficacy and outcomes of outpatient parenteral antimicrobial therapy (OPAT) in neonates (≤28 days of age), compared with older infants (1-12 months of age). DESIGN: A prospective 8-year observational study from September 2012 to September 2020. SETTING: The Hospital-in-the-Home (HITH) programme of the Royal Children's Hospital Melbourne. PATIENTS: Neonatal patients (≤28 days of age) were compared with older infants (1-12 months of age) receiving OPAT. INTERVENTIONS: Data were collected including demographics, diagnosis, type of venous access and antibiotic choice. MAIN OUTCOME MEASURES: Success of OPAT, antibiotic appropriateness, complications and readmission rate. RESULTS: There were 76 episodes for which neonates were admitted to HITH for OPAT, and 405 episodes for older infants. Meningitis was the most common diagnosis in both groups (59% and 35%, respectively); the most frequently prescribed antibiotic was ceftriaxone for both groups (61% and 49%). A positive bacterial culture was less frequent in neonates (38% vs 53%, p=0.02). Vascular access complication rate was 19% in neonates compared with 13% in older infants (p=0.2) with no central line-associated bloodstream infection in either group. Rates of appropriate antibiotic prescribing were similarly high between groups (93% vs 90%, p=0.3). The OPAT course was successfully completed in 74 of 74 (100%) neonates and 380 of 396 (96%) older infants (p=0.09). The unplanned readmission rate was low: 4 of 76 (5%) neonates and 27 of 405 (7%) older infants. CONCLUSIONS: OPAT is a safe and effective way of providing antibiotics to selected clinically stable neonatal patients. While appropriate antibiotic use was common, improvements can still be made.

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.

The characteristics of SARS-CoV-2-positive children who presented to Australian hospitals during 2020: a PREDICT network study.

OBJECTIVES: To examine the epidemiological and clinical characteristics of SARS-CoV-2-positive children in Australia during 2020. DESIGN, SETTING: Multicentre retrospective study in 16 hospitals of the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network; eleven in Victoria, five in four other Australian states. PARTICIPANTS: Children aged 0-17 years who presented to hospital-based COVID-19 testing clinics, hospital wards, or emergency departments during 1 February - 30 September 2020 and who were positive for SARS-CoV-2. MAIN OUTCOME MEASURES: Epidemiological and clinical characteristics of children positive for SARS-CoV-2. RESULTS: A total of 393 SARS-CoV-2-positive children (181 girls, 46%) presented to the participating hospitals (426 presentations, including 131 to emergency departments [31%]), the first on 3 February 2020. Thirty-three children presented more than once (8%), including two who were transferred to participating tertiary centres (0.5%). The median age of the children was 5.3 years (IQR, 1.9-12.0 years; range, 10 days to 17.9 years). Hospital admissions followed 51 of 426 presentations (12%; 44 children), including 17 patients who were managed remotely by hospital in the home. Only 16 of the 426 presentations led to hospital medical interventions (4%). Two children (0.5%) were diagnosed with the paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). CONCLUSION: The clinical course for most SARS-CoV-2-positive children who presented to Australian hospitals was mild, and did not require medical intervention.

What is the risk of missing orbital cellulitis in children?

BACKGROUND: Preseptal cellulitis can be difficult to distinguish from orbital cellulitis in children. The majority of patients with periorbital infections are admitted for intravenous antibiotics. This study aimed to investigate the risk of missing orbital cellulitis and the outcomes of missed patients. METHODS: A prospective cohort study of children aged 3 months to 18 years diagnosed with preseptal cellulitis over 5 years. Data were collected prospectively, including demographics, clinical features and outcomes. RESULTS: There were 216 children diagnosed with preseptal cellulitis. 75 (35%) were treated with oral antibiotics and 141 (65%) with intravenous antibiotics. 5 (2%) children who were hospitalised were subsequently determined to have orbital cellulitis. All 5 children were either a young infant with difficult eye examination, or had headache or vomiting. CONCLUSION: The risk of missing orbital cellulitis is low. Young infants with difficult eye examination or the presence of headache or vomiting should increase suspicion of orbital cellulitis.

SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children's hospital.

OBJECTIVE: International studies describing COVID-19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS-CoV-2 at a large Australian tertiary children's hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children's Hospital, Melbourne, Australia. It included all paediatric patients (aged 0-18 years) who presented to the ED or the Respiratory Infection Clinic (RIC) and were tested for SARS-CoV-2. The 30-day study period commenced after the first confirmed positive case was detected at the hospital on 21 March 2020, until 19 April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS-CoV-2 testing was performed in ED (331 [76%]) or RIC (102 [24%]). There were four (0.9%) who had positive SARS-CoV-2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS-CoV-2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS-CoV-2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID-19 were identified in 4/4 SARS-CoV-2 positive patients and 47/429 (11%) SARS-CoV-2 negative patients. CONCLUSION: Our study identified a very low rate of SARS-CoV-2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS-CoV-2 negative had comorbidities.

Impact of expanding a paediatric OPAT programme with an antimicrobial stewardship intervention.

BACKGROUND: As treatment out of hospital with outpatient parenteral antimicrobial therapy (OPAT) increases, so too does the risk for patients of being less visible, with potential for suboptimal care. OBJECTIVES: We aimed to compare pre-expansion and post-expansion (1) successful completion, complications and (2) the impact of an OPAT-specific antimicrobial stewardship (AMS) intervention to mitigate inappropriate antibiotic prescribing. DESIGN: A prospective longitudinal study during two consecutive 12-month periods: period A (1 August 2012 to 31 July 2013) and period B (1 August 2013 to 31 July 2014). SETTING: The Hospital-in-the-Home (HITH) programme at The Royal Children's Hospital Melbourne. PARTICIPANTS: All patients who received OPAT during the study period. INTERVENTIONS: Between the two periods, the programme expanded from 16 to 32 patients/day. To coincide with this, a combined AMS intervention was introduced: (1) OPAT-specific guidelines and (2) active review of OPAT prescriptions and input by Paediatric Infectious Diseases. MAIN OUTCOMES: Successful completion of OPAT, OPAT-related complications, readmission, length of stay and antibiotic appropriateness. RESULTS: Over 2 years, 646 patients (47% female, median age 7 years) were treated via OPAT for 754 episodes. Patient episodes increased from 254 in period A to 500 in period B, with proportional increases in infants under 1 month and immunocompromised patients. OPAT was successfully completed in 245/251 (98%) versus 473/482 (98%) (OR 1.8, 95% CI 0.7 to 4.5, p=0.3). OPAT-related complications remained low: intravenous catheter-associated complications 16/138 (12%) versus 41/414 (10%), and antibiotic-associated complications 0/254 (0%) versus 2/500 (0.4%). Despite the increase in activity, with the AMS intervention, overall appropriate antibiotic prescribing remained high: 71% versus 76%. Inappropriately long durations reduced from 30/312 (10%) to 37/617 (6%) (OR 0.6, 95% CI 0.4 to 0.99, p=0.04), and median number of days on broad-spectrum antibiotics from 11 (IQR 8-24.5) to 8 (IQR 5-11). CONCLUSION: During a period of substantial expansion, we maintained clinical outcomes. A modest AMS intervention reduced some but not all aspects of inappropriate antibiotic prescribing.

Effect of seminal plasma or transforming growth factor on bovine endometrial cells.

Semen induces post-coital inflammation of the endometrium in several species. Post-coital inflammation is proposed to alter the endometrial environment of early pregnancy, mediate embryonic development and modulate the maternal immune response to pregnancy. In cattle, it is common for pregnancies to occur in the absence of whole semen due to the high utilization of artificial insemination. Here, we have utilized a cell culture system to characterize semen-induced expression of inflammatory mediators in bovine endometrial cells and test the efficacy of transforming growth factor beta as the active agent in mediating any such change. We hypothesize that seminal plasma-derived transforming growth factor beta increases the expression of inflammatory mediators in bovine endometrial cells. Initially, we describe a heat-labile cytotoxic effect of seminal plasma on BEND cells, and a moderate increase in IL1B and IL6 expression. In addition, we show that transforming growth factor beta is present in bovine semen and can increase the expression of endometrial IL6, whereas blocking transforming growth factor beta in semen ameliorates this effect. However, intra-uterine infusion of seminal plasma, sperm or transforming growth factor beta did not alter the endometrial expression of inflammatory mediators. We conclude that bovine semen can modulate endometrial gene expression in vitro, which is partially due to the presence of transforming growth factor beta. It is likely that additional, unidentified, bioactive molecules in semen can alter the endometrial environment. Characterizing bioactive molecules in bovine semen may lead to the development of additives to improve artificial insemination in domestic species.

The effect of ferulic acid against lead-induced oxidative stress and DNA damage in kidney and testes of rats.

Oxidative stress is an imbalance between free radicals and antioxidants which leads to reactive oxygen species (ROS) production in cells. Reactive oxygen species contains oxygen radicals that easily react with other molecules in the biological system. For decades, lead acetate (Pb(C2H3O2)2) is used as an additive for many widely used chemical products such as insecticides, hair dyes, and cosmetics; however, contact with lead acetate may irritate skin, eyes, and mucous membranes.In the present study, the antioxidant and anti-inflammatory effect of using ferulic acid to inhibit lead acetate-induced toxicity in rats is investigated. Lead acetate was orally given at a dose of 20 mg/kg body weight for 10 days, either alone or with ferulic acid at dose 25 mg/kg. Serum luteinizing hormone (LH), total testosterone, and follicle-stimulating hormone (FSH) levels were measured. Also, reactive oxygen species (ROS), lipid peroxidation (LPO), total antioxidant capacity (TAC), and catalase (CAT) activities were determined. In addition, histopathological changes of testes and kidney were examined. Results showed that administration of lead acetate induced oxidative stress through attenuation of luteinizing hormone, total testosterone, and follicle-stimulating hormone levels in serum. Moreover, the kidney and testes of lead acetate-treated animals exhibited elevation of ROS level, lipid peroxide levels, as well as lysosomal enzyme activity such acid phosphatase and N-acetyl-ß-glucosminidase. DNA fragmentation and histological changes were also observed in lead acetate-treated group. In contrast, ferulic acid treatment reduced the deleterious effects induced by lead acetate in both testes and kidney tissues. These results illustrated that ferulic acid has a protective action against toxicity caused by lead acetate in rats. In conclusions, ferulic acid may have future therapeutic relevance in the prevention of lead acetate-induced testicular and renal toxicity in rats.

Intravenous ceftriaxone at home versus intravenous flucloxacillin in hospital for children with cellulitis: a cost-effectiveness analysis.

BACKGROUND: Outpatient parenteral antibiotic therapy after hospital admission is increasingly popular, but its use to avoid admission to hospital altogether by treating patients wholly as outpatients remains uncommon in children. One reason for the low use of treatment at home is the scarcity of evidence of its cost-effectiveness. In this planned follow-up analysis of the Cellulitis at Home or Inpatient in Children from the Emergency Department (CHOICE) trial, we aimed to assess the cost-effectiveness of an admission avoidance pathway, in which children were treated at home, compared with standard hospital care for the intravenous treatment of moderate or severe cellulitis. METHODS: We did a cost-effectiveness analysis to compare home treatment with intravenous ceftriaxone versus hospital treatment with intravenous flucloxacillin in children aged 6 months to 18 years who had presented to the emergency department at The Royal Children's Hospital, Melbourne, VIC, Australia, with moderate or severe uncomplicated cellulitis. We included costs from two sources: institutional costs at a patient level and expenses incurred by families. We measured effectiveness with quality-adjusted life years (QALYs), which we derived from the Child Health Utility 9D questionnaire, and a clinical outcome of treatment failure, which was the primary outcome of the CHOICE trial. We planned to calculate the incremental cost-effectiveness ratio, defined as the difference between groups in total cost divided by the difference between groups in effectiveness. The CHOICE trial is registered at ClinicalTrials.gov, number NCT02334124. FINDINGS: We included 180 children who comprised the per-protocol population in the CHOICE trial: 89 children in the home group and 91 children in the hospital group. The institutional cost per patient per episode was significantly lower in the home group than in the hospital group (AUS$1965 vs $3775; p<0·0001). The mean cost incurred per family was $182 for the home group and $593 for the hospital group (p<0·0001). Both measures of effectiveness were significantly better in the home group than in the hospital group: QALYs were 0·005 for the home group versus 0·004 for the hospital group (p<0·0001), and treatment failure occurred in one (1%) patient in the home group versus seven (8%) patients in the hospital group (risk difference -6·5%, 95% CI -12·4 to -0·7; p=0·029). Calculating the incremental cost-effectiveness ratio was thus deemed redundant. INTERPRETATION: Treatment at home was less costly and more effective than standard hospital care for children with moderate or severe cellulitis. These findings support development of this admission avoidance pathway in hospitals. FUNDING: The Royal Children's Hospital Foundation, Murdoch Children's Research Institute.

Efficacy and safety of intravenous ceftriaxone at home versus intravenous flucloxacillin in hospital for children with cellulitis (CHOICE): a single-centre, open-label, randomised, controlled, non-inferiority trial.

BACKGROUND: Outpatient parenteral antimicrobial therapy in children is common despite no evidence of its efficacy or safety from clinical trials. We aimed to compare the efficacy and safety of intravenous antibiotic therapy at home with that of standard treatment in hospital for children with moderate to severe cellulitis. METHODS: The Cellulitis at Home or Inpatient in Children from the Emergency Department (CHOICE) trial was a randomised, controlled, non-inferiority trial in children aged 6 months to 18 years who presented to the emergency department at The Royal Children's Hospital (Melbourne, VIC, Australia) with uncomplicated moderate to severe cellulitis. Participants were randomly assigned to receive either intravenous ceftriaxone (50 mg/kg once daily) at home or intravenous flucloxacillin (50 mg/kg every 6 h) in hospital with web-based randomisation, stratified by age and periorbital cellulitis. The primary outcome was treatment failure, which was defined as no clinical improvement or occurrence of an adverse event, resulting in a change in empiric antibiotics within 48 h of the first dose. Secondary outcomes included adverse events and acquisition of antibiotic-resistant bacteria. Outcomes were assessed in all randomised participants with outcome data (intention-to-treat population) and in all individuals who received treatment as allocated and did not have any major protocol violations (per-protocol population). For home treatment to be non-inferior to hospital treatment, the difference between groups in the proportion of children with treatment failure in the intention-to-treat population had to be less than 15%. This trial is registered with ClinicalTrials.gov, number NCT02334124. FINDINGS: Between Jan 9, 2015, and June 15, 2017, we screened 1135 children for eligibility, of whom 190 were randomly assigned to receive ceftriaxone at home (n=95) or flucloxacillin in hospital (n=95). The intention-to-treat analysis comprised 188 children (93 in the home group and 95 in the hospital group) because two children in the home group were found to be ineligible after randomisation and were excluded. Treatment failure occurred in two (2%) children in the home group and in seven (7%) children in the hospital group (risk difference -5·2%, 95% CI -11·3 to 0·8, p=0·088). In the per-protocol analysis, treatment failure occurred in one (1%) of 89 children in the home group and in seven (8%) of 91 children in the hospital group (-6·5%, -12·4 to -0·7). Fewer children treated at home than in hospital had an adverse event (two [2%] vs ten [11%]; p=0·048). There was no difference between groups in rates of nasal acquisition of meticillin-resistant Staphylococcus aureus or gastrointestinal acquisition of extended-spectrum ß-lactamase-producing bacteria or Clostridium difficile after 3 months. INTERPRETATION: Home treatment with intravenous ceftriaxone is not inferior to treatment in hospital with intravenous flucloxacillin for children with cellulitis. The standard of care for the intravenous treatment of uncomplicated cellulitis in children should be home or outpatient care when feasible. FUNDING: The Royal Children's Hospital Foundation and Murdoch Children's Research Institute.

Development and Validation of a Cellulitis Risk Score: The Melbourne ASSET Score.

: media-1vid110.1542/5972298232001PEDS-VA_2018-1420Video Abstract BACKGROUND: The evidence is unclear about the optimal route of treatment for children with cellulitis, specifically how to assess the risk of moderate-to-severe cellulitis requiring intravenous (IV) antibiotics. We aimed to derive and validate a cellulitis risk assessment scoring system to guide providers as to which patients require IV antibiotics. METHODS: This was a prospective cohort study of children presenting to the emergency department aged 6 months to 18 years diagnosed with cellulitis from January 2014 to August 2017. Patients were divided into 2 groups based on route of antibiotics at 24 hours (the predetermined gold standard). Demographics and clinical features were compared. Clinicians were surveyed about which features they used to decide whether to start IV antibiotics. Combinations of differentiating features were plotted on receiver operating characteristic curves. RESULTS: There were 285 children in the derivation cohort used to create the Melbourne Area, Systemic features, Swelling, Eye, Tenderness (ASSET) Score, which has a maximum score of 7. The area under the curve was 0.86 (95% confidence interval 0.83-0.91). Using a cutoff score of 4 to start IV antibiotics yielded the highest correct classification of 80% of patients (sensitivity 60%; specificity 93%). This score was validated in 251 children and maintained a robust area under the curve of 0.83 (95% confidence interval 0.78-0.89). CONCLUSIONS: The Melbourne ASSET Score was derived and validated for cellulitis in children to guide clinicians regarding when to start IV antibiotics. Although intended for widespread use, if limitations exist in other settings, it is designed to allow for refinement and is amenable to local impact analysis.

Selected Children With Complicated Acute Urinary Tract Infection May Be Treated With Outpatient Parenteral Antibiotic Therapy at Home Directly From the Emergency Department.

BACKGROUND: Outpatient parenteral antimicrobial therapy offers the option of treating children requiring intravenous antibiotics for acute urinary tract infection (UTI)/pyelonephritis at home. We aimed to determine the outcomes of treating patients with UTI/pyelonephritis using outpatient parenteral antimicrobial therapy directly from the emergency department (ED) without admission to hospital. METHODS: This was a retrospective study (August 2012-July 2016) of children with UTI/pyelonephritis treated with parenteral antibiotics via a peripheral cannula directly from ED to home under a hospital-in-the home (HITH) program. Data collection included demographics, clinical features, length of stay, complications, and readmissions to hospital. RESULTS: There were 62 patient episodes of UTI/pyelonephritis transferred directly from ED to HITH. Fifty-eight (94%) had systemic features including fever, vomiting and/or tachycardia. Eighteen (29%) patients had an underlying condition. Nine (15%) received intravenous fluids and 8 (13%) antiemetics in ED. The outpatient parenteral antimicrobial therapy course was successfully completed in 56 (90%) patients. Of 6 (10%) patients who were readmitted, 2 were discharged within 24 hours, and none were severely unwell. Two (3%) had a blocked cannula, with no antibiotic complications. HITH patients were treated for a combined total of 142 days at home resulting in a cost saving of Australian dollar 108,914 (US dollar 82,775). However, only 8% of children deemed to require a course of intravenous antibiotics were transferred directly home from ED. Compared with patients concurrently admitted to hospital, fewer on HITH were less than 1 year of age (13% vs. 33%; odds ratio: 0.3; P < 0.01). CONCLUSIONS: Selected patients presenting to ED with UTI/pyelonephritis may be treated directly via HITH, including some with underlying conditions and/or systemic features.

Seminal plasma modulates expression of endometrial inflammatory meditators in the bovine†.

Seminal plasma has conventionally been viewed as a transport and survival medium for mammalian sperm; however, its role now extends beyond this process to actively targeting female tissues. Studies in rodents, swine, and humans demonstrate that seminal plasma induces molecular and cellular changes within the endometrium or cervix following insemination. Seminal-plasma-induced alterations to the maternal environment have been theorized to facilitate embryo development, modulate maternal immunity toward the conceptus, and potentially improve pregnancy success. It is unknown if bovine seminal plasma modulates the uterine environment following insemination in the cow, where routine use of artificial insemination reduces maternal exposure to seminal plasma. We hypothesize that seminal plasma modulates the expression of inflammatory mediators in the endometrium, altering the maternal environment of early pregnancy. In vitro, seminal plasma altered intact endometrial explant expression of CSF2, IL1B, IL6, IL17A, TGFB1, IFNE, PTGS2, and AKR1C4. Furthermore, endometrial epithelial cell CSF2, CXCL8, TGFB1, PTGS2, and AKR1C4 expression were increased after seminal plasma exposure, while endometrial stromal cell CSF2, IL1B, IL6, CXCL8, IL17A, TGFB1, PTGS2, and AKR1C4 expression were increased following seminal plasma exposure. Endometrial expression of IL1B was increased in the cow 24 h after uterine infusion of seminal plasma, while other evaluated inflammatory mediators remained unchanged. These data indicate that seminal plasma may induce changes in the bovine endometrium in a temporal manner. Understanding the role of seminal plasma in modulating the maternal environment may aid in improving pregnancy success in cattle.