A paediatric hospital care AMC report for Northern Ireland.

BACKGROUND: Antimicrobial stewardship (AMS) is high on the agenda of healthcare policymakers and measurement of its impact is reliant on antimicrobial consumption (AMC) and antimicrobial resistance (AMR) data. Recent AMC reports have identified high antimicrobial prescribing rates in Northern Ireland (NI), compared with UK and European countries, but no separate paediatric data were reported. OBJECTIVES: To describe AMC trends in paediatric and neonatal inpatient care in NI between September 2015 and September 2020, in order to: (i) create a paediatric-specific AMC report and benchmark for future AMS interventions; and (ii) develop an action plan for establishing paediatric AMC/AMR surveillance in NI. METHODS: AMC data, measured in monthly DDD, as well as hospital bed occupancy and admissions statistics were analysed. Hospital AMC was measured using several metrics and subdivided by level of paediatric and neonatal care, and by proportion of antibiotic use according to the WHO AWaRe classification. RESULTS: Paediatric-specific consumption in hospital care was 0.3-0.42 DDD per 1000 inhabitants per day, representing approximately 10% of total AMC. There was variation in AMC rates between similar units. In some areas, an increasing proportion of Watch and Reserve antibiotic consumption was observed. CONCLUSIONS: A baseline AMC dataset for paediatric and neonatal units across NI has been created. Continuous prospective collection and analysis of these data, along with AMR surveillance, would strengthen paediatric AMS programmes and provide crucial information for their resourcing. It is hoped that this report will act as a catalyst to galvanize paediatric AMS efforts regionally.

How to interpret a paediatric blood culture.

Blood culture is one of the most important diagnostic tests in medicine, considering the significant morbidity and mortality associated with bloodstream infection (BSI). However, it is an often misused and misinterpreted test in everyday paediatric practice. In this article, we explore the evidence related to paediatric blood cultures, with the aim of providing clear and clinically-relevant recommendations for its judicious use.

PRDX3 is associated with metastasis and poor survival in uveal melanoma.

AIMS: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and 40% develop fatal metastatic disease. Overexpression of thioredoxin-dependent peroxidase reductase (PRDX3) has been implicated in several cancers, including prostate, breast, colorectal and lung cancer. The aim of this study was to compare the immunohistochemical expression of PRDX3 in formalin-fixed, paraffin-embedded (FFPE) primary UM tissues of patients who did and did not develop metastatic disease. METHODS: Immunohistochemical staining of PRDX3 was performed on FFPE tissue microarray samples of 92 primary UM tumours from patients who did and did not develop metastatic disease. The immunohistochemical staining was assessed by two observers who were blinded to all clinicopathological and cytogenetic details including metastatic/non-metastatic information. Based on a scoring system, expression of PRDX3 was graded as high or low. RESULTS: There were 55 tumours (59.8%) from patients who developed metastatic disease, while 37 (40.2%) were from patients who did not develop metastasis. A statistically significant difference in PRDX3 expression was observed in patients who did and did not develop metastasis (p=0.001). A significant positive correlation between high PRDX3 expression and metastasis was observed (p=0.001). A significant negative correlation between PRDX3 expression and survival was found (p=0.005). Kaplan-Meier survival analysis showed a statistically significant difference in overall survival between tumours that demonstrated low and high expression of PRDX3 (67.61 vs 130.64 months, respectively, p=0.013). CONCLUSIONS: High immunohistochemical expression of PRDX3 in primary UM tissue is associated with metastasis and poor survival.

Emergency department attendance following 4-component meningococcal B vaccination in infants.

INTRODUCTION: In September 2015, the UK became the first country in the world to introduce the 4-component meningococcal B vaccine(4CMenB) into the routine vaccine schedule for infants. 4CMenB is known to cause fever in infants. Infants presenting with fever, particularly those under 3 months, have a significant risk of serious bacterial infection(SBI). METHOD: Between September 2015 and January 2016, we performed a prospective audit of management of infants between 30 and 180 days attending the regional paediatric emergency department(ED) in Northern Ireland, within 4 days of receiving 4CMenB. RESULTS: 35 ED attendances in infants aged 30-180 days were due to symptoms occurring after primary vaccinations including 4CMenB, representing an estimated 0.8% of the vaccinated population in the catchment area. 86% of infants presented after the first vaccine and parents reported giving paracetamol to 94% of infants. 80% of infants presented with fever. Blood tests were performed in 62% of infants and leucocytosis was present in 73%. All cultures taken were negative and 51% were admitted to hospital. 100% of final diagnoses were vaccine related (diagnosis made by exclusion). DISCUSSION: In this study, an estimated 0.8% of the vaccinated population in the catchment area attended ED with symptoms occurring after primary vaccinations including 4CMenB. Infants with fever have a higher risk of SBI, but infants with fever in the post-vaccination period may not have the same risk. Further data are essential to inform national guidelines on investigation and management of fever in infants following vaccination with 4CMenB, possibly incorporating a less-invasive approach.

Rhabdomyolysis Complicating Typhoid Fever in A Child and Review of the Literature.

Typhoid fever is an important cause of morbidity and mortality in the developing world, particularly in children, but is infrequently observed in the developed world and can occur in patients without a significant travel history. Rhabdomyolysis as a complication has rarely been reported, and never in a child. A child with Salmonella enterica serovar Typhi septicemia, complicated by rhabdomyolysis, encephalopathy and pancreatitis is described and all 15 reported cases to date are summarized.

Australia-wide Point Prevalence Survey of Antimicrobial Prescribing in Neonatal Units: How Much and How Good?

BACKGROUND: There is increasing recognition of the threat to neonatal patients from antibiotic resistance. There are limited data on antimicrobial prescribing practices for hospitalized neonates. We aimed to describe antimicrobial use in hospitalized Australian neonatal patients, and to determine its appropriateness. METHODS: Multicentre single-day hospital-wide point prevalence survey in 2012, in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. The appropriateness of antimicrobial prescriptions was also assessed. All patients admitted at 8 am on the survey day, in 6 neonatal units in tertiary children's hospitals across 5 states, were included in an analysis of the quantity and quality of all antimicrobial prescriptions. RESULTS: The point prevalence survey included 6 neonatal units and 236 patients. Of 109 patients (46%) receiving at least 1 antimicrobial, 66 (61%) were being treated for infection, with sepsis the most common indication. There were 216 antimicrobial prescriptions, 134 (62%) for treatment of infection and 82 (38%) for prophylaxis, mostly oral nystatin. Only 15 prescriptions were for targeted as opposed to empirical treatment. Penicillin and gentamicin were the most commonly prescribed antibiotics, with vancomycin third most common. Half of all treated patients were receiving combination antimicrobial therapy. There was marked variation in vancomycin and gentamicin dosing. Overall, few prescriptions (4%) were deemed inappropriate. CONCLUSION: This is the first Australia-wide point prevalence survey of neonatal antimicrobial prescribing in tertiary children's hospitals. The findings highlight positive practices and potential targets for quality improvement.

Increasing pyomyositis presentations among children in Queensland, Australia.

BACKGROUND: Pyomyositis, usually associated with tropical climates, occurs less commonly in temperate regions and is most often caused by Staphylococcus aureus. Several community-acquired methicillin-resistant S. aureus (CA-MRSA) clones have emerged in Queensland since the beginning of the century, and they now account for a significant proportion of invasive staphylococcal infection. This study aims to describe trends in the rate of presentation, and the clinical and diagnostic features of pyomyositis, and to determine if trends are attributed to the emergence of CA-MRSA or other factors. METHODS: A 10-year retrospective cohort study of all patients presenting to Mater Children's Hospital in Brisbane, Queensland, with pyomyositis between July 2002 and July 2012, was conducted. Data were collected for clinical features, microbiology, diagnostic tests, management and outcome. Trends in incidence, and clinical and diagnostic features of pyomyositis were analyzed. RESULTS: Thirty-four cases of pyomyositis were identified. There was a male predominance (79%), and the vertebro-pelvic muscles were most often affected. The rate of pyomyositis increased significantly during the study period from a rate of 2.04 cases per 10,000 emergency department admissions in the first quarter of the study, to 8.73 cases per 10,000 in the final quarter (peak rate 13.5 cases per 10,000 in 2008). A causative organism was identified in 22 cases, most commonly methicillin-susceptible S. aureus with CA-MRSA identified in 4 cases. Patients who required surgical intervention had longer hospital admission, longer time to resolution of inflammatory markers and a higher risk of complication at follow-up. CONCLUSION: This study demonstrates an increasing incidence of pyomyositis in a temperate region, which is not attributable to the emergence of CA-MRSA. The reasons for this change in incidence are not clear.

Australia-wide point prevalence survey of the use and appropriateness of antimicrobial prescribing for children in hospital.

OBJECTIVES: To describe antimicrobial use in hospitalised Australian children and to analyse the appropriateness of this antimicrobial use. DESIGN: Multicentre single-day hospital-wide point prevalence survey, conducted in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. SETTING: Eight children's hospitals across five Australian states, surveyed during late spring and early summer 2012. PATIENTS: Children and adolescents who were inpatients at 8 am on the day of the survey. MAIN OUTCOME MEASURES: Quantity and quality of antimicrobial prescribing. RESULTS: Of 1373 patients, 631 (46%) were prescribed at least one antimicrobial agent, 198 (31%) of whom were < 1 year old. The highest antimicrobial prescribing rates were in haematology and oncology wards (76% [95/125]) and paediatric intensive care units (55% [44/80]). Of 1174 antimicrobial prescriptions, 550 (47%) were for community-acquired infections, 175 (15%) were for hospital-acquired infections and 437 (37%) were for prophylaxis. Empirical treatment accounted for 72% of antimicrobial prescriptions for community-acquired infections and 58% for hospital-acquired infections (395 and 102 prescriptions, respectively). A total of 915 prescriptions (78%) were for antibacterials; antifungals and antivirals were predominantly used for prophylaxis. The most commonly prescribed antibacterials were narrow-spectrum penicillins (18% [164 prescriptions]), ß-lactam-ß-lactamase inhibitor combinations (15% [136]) and aminoglycosides (14% [128]). Overall, 957 prescriptions (82%) were deemed appropriate, but this varied between hospitals (range, 66% [74/112]) to 95% [165/174]) and specialties (range, 65% [122/187] to 94% [204/217]). Among surgical patients, 65 of 187 antimicrobial prescriptions (35%) were deemed inappropriate, and a common reason for this was excessive prophylaxis duration. CONCLUSION: A point prevalence survey is a useful cross-sectional method for quantifying antimicrobial use in paediatric populations. The value is significantly augmented by adding assessment of prescribing quality.

Balamuthia mandrillaris Encephalitis: Survival of a Child With Severe Meningoencephalitis and Review of the Literature.

Balamuthia mandrillaris causes granulomatous amoebic encephalitis, which is frequently fatal. There are few reports of survival in children. A 4-year-old child developed severe meningoencephalitis with multiple intracranial ring-enhancing lesions. Empiric therapy was commenced after a biopsy was performed, and the patient had a good clinical response. Molecular testing and indirect immunofluorescence later confirmed the diagnosis of Balamuthia encephalitis. Diagnosis of Balamuthia encephalitis is often delayed. The literature is reviewed with particular reference to reported survival. Prompt tissue diagnosis and initiation of therapy are common features among survivors. In previous reports, miltefosine was not used to treat children, but it was well tolerated in this case and should be considered as a therapeutic option.

Proteomics in uveal melanoma.

Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

Effects of prostaglandin F(2α) on adipocyte biology relevant to graves' orbitopathy.

BACKGROUND: In Graves' orbitopathy (GO), increased proliferation, excess adipogenesis, and hyaluronan overproduction produce GO exophthalmos. Enophthalmos occurs in some glaucoma patients treated with Bimatoprost (prostaglandin F2α, PGF2α) eye drops. We hypothesized that enophthalmos is secondary to reductions in orbital tissue proliferation, adipogenesis, and/or increased lipolysis. We aimed to determine which of these is affected by PGF2α by using the 3T3-L1 murine preadipocyte cell line and primary human orbital fibroblasts (OFs) from GO patients (n=5) and non-GO (n=5). METHODS: 3T3-L1 cells and orbital OFs were cultured alone or with PGF2α (all experiments used 10(-8) to 10(-6) M) and counted on days 1/2/3 or 5, respectively; cell cycle analysis (flow cytometry) was applied. Adipogenesis (in the presence/absence of PGF2α) was evaluated (day 7 or 15 for 3T3-L1 and primary cells, respectively) morphologically by Oil Red O staining and quantitative polymerase chain reaction measurement of adipogenesis markers (glycerol-3-phosphate dehydrogenase and lipoprotein lipase, respectively). For lipolysis, in vitro-differentiated 3T3-L1 or mature orbital adipocytes were incubated with norepinephrine and PGF2α and free glycerol was assayed. Appropriate statistical tests were applied. RESULTS: The population doubling time of 3T3-L1 was 27.3±1.4 hours-significantly increased by dimethyl sulfoxide 0.02% to 44.6±4.8 hours (p=0.007) and further significantly increased (p=0.049 compared with dimethyl sulfoxide) by 10(-8) M PGF2α to 93.6±19.0 hours, indicating reduced proliferation, which was caused by prolongation of G2/M. GO OFs proliferated significantly more rapidly than non-GO (population doubling time 5.36±0.34 or 6.63±0.35 days, respectively, p=0.035), but the proliferation of both was significantly reduced (dose dependent from 10(-8) M) by PGF2α, again with prolongation of G2/M. Adipogenesis in 3T3-L1 cells was minimally affected by PGF2α when assessed morphologically, but the drug significantly reduced transcripts of the glycerol-3-phosphate dehydrogenase differentiation marker. GO OFs displayed significantly higher adipogenic potential than non-GO, but in both populations, adipogenesis, evaluated by all 3 methods, was significantly reduced (dose dependent from 10(-8) M) by PGF2α. There was no effect of PGF2α on basal or norepinephrine-induced lipolysis, in 3T3-L1 or human OFs, either GO or non-GO. CONCLUSIONS: The results demonstrate that PGF2α significantly reduces proliferation and adipogenesis and that human OFs are more sensitive to its effects than 3T3-L1. Consequently, PGF2α could be effective in the treatment of GO.

Differential expression of fourteen proteins between uveal melanoma from patients who subsequently developed distant metastases versus those who did Not.

PURPOSE: To compare the proteomic profiles of two categories of primary uveal melanoma tissue samples; those from patients who have subsequently developed metastatic disease and those who have not. METHODS: Two-dimensional difference gel electrophoresis (2D DIGE) was performed on 25 uveal melanoma tissue specimens (minimum follow-up of 7 years) comparing nine uveal melanoma tumors from patients who developed metastatic disease and 16 from those who did not. Most of the tumors which metastasized also exhibited chromosome 3 monosomy. Selected differentially expressed proteins were further followed up by immunohistochemistry and functional validation in vitro using siRNA. RESULTS: Proteomic analysis revealed 14 statistically significant differentially expressed proteins, with nine showing increased expression (PDIA3, VIM/HEXA, SELENBP1, ENO1, CAPZA1, ERP29, TPI1, PARK7, and FABP3) and five showing decreased expression (EIF2S, PSMA3, RPSA, TUBB, and TUBA1B) in uveal melanomas that subsequently metastasized compared with those that did not. Immunohistochemical analysis was performed for six of the differentially expressed proteins and gave similar results to the 2D DIGE study for two of these proteins, fatty acid-binding protein, heart-type (FABP3) and triosephosphate isomerase (TPI1). siRNA knockdown in the 92.1 uveal melanoma cell line confirmed a functional role for FABP3 and TPI1 in invasion in vitro. CONCLUSIONS: Proteomic analysis identified proteins differentially expressed in uveal melanoma that will subsequently metastasize, some of which appear to have a functional role in invasion. These results may contribute to better predictive tests (along with genetic analysis) and to the identification of new therapeutic targets.

Beware the empty curette!

BACKGROUND AND OBJECTIVE: Chalazions are a common occurrence in the eyelids due to chronic inflammation in the tarsal plate. Treatment of non-resolving cases may involve incision and curettage. Chalazions that are recurrent should arouse suspicion. We present a case of a pleomorphic adenoma of the palpebral portion of the lacrimal gland, which was misdiagnosed as a chalazion. PATIENT AND METHODS: A 41-year-old Caucasian lady initially presented with a swelling in the outer part of her right upper eyelid. A diagnosis of chalazion was made and two attempts at incision and curettage failed to resolve the lesion. She was then referred to the oculoplastics/adnexal unit. A more detailed examination revealed involvement of the palpebral part of her lacrimal gland. A CT-scan confirmed this and she proceeded to have a lateral orbitotomy to remove the tumour. RESULTS: Histological confirmation of a pleomorphic adenoma of the palpebral portion of the lacrimal gland was obtained. The lacrimal gland had been completely excised. CONCLUSION: Persistent or recurrent meibomian cyst should be treated with suspicion. A careful orbital examination including lid eversion should always be performed to outrule a more sinister pathology.