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Aims: Despite the declining incidence of acute post‐streptococcal glomerulonephritis (APSGN) in Australia, there is still a significant burden of disease amongst Aboriginal and Torres Strait Islander people in the Northern Territory. Childhood APSGN has been highlighted as a predictor of chronic kidney disease in this population. We aimed to describe clinical characteristics and outcomes of hospitalised children with APSGN in the Northern Territory. Methods: Single‐centre, retrospective cohort study of children (<18 years) with APSGN admitted to a tertiary hospital in the Top End of the Northern Territory between January 2012 and December 2017. Cases were confirmed using the Centre for Disease Control case definition guidelines. Data were extracted from the case notes and electronic medical records. Results: There were 96 cases of APSGN with median age of 7.1 years (interquartile range (IQR) 6.7–11.4). Majority were Aboriginal and Torres Strait Islander (90.6%) and from rural and remote areas (82.3%). Preceding skin infections were identified in 65.5% and sore throat in 27.1%. Severe complications included hypertensive emergencies (37.4%), acute kidney injury (43.8%) and nephrotic‐range proteinuria (57.7%). All children improved from their acute illness with supportive medical therapy; however, only 55 out of 96 (57.3%) children were followed up within 12 months of their acute illness. Conclusions: APSGN disproportionately affects Aboriginal and Torres Strait Islander children and highlights the need for continued and improved public health response. There is room for significant improvement in the medium‐ and long‐term follow‐up of affected children. [ABSTRACT FROM AUTHOR]

While I M. ulcerans i infections are usually managed with oral therapy, this patient required prolonged intravenous therapy and multiple medication changes due to adverse effects, drug interactions, and the development of oral medication refusal. She tolerated the intravenous therapy well, with no central line-associated complications, and the only adverse reaction to intravenous therapy a borderline prolonged PR interval which remained stable throughout treatment. I Mycobacterium ulcerans i is a complex infection endemic to Victoria and far north Queensland, but may occur elsewhere in Australia, necessitating high clinical suspicion in patients with chronic ulcers. [Extracted from the article]

In case 1, we hypothesise that the cephalohaematoma developed into subgaleal abscess with bacterial seeding from the antecedent urinary tract infection. The blood culture was also negative, white cell count (WCC) was 5.7 × 10 SP 9 sp /L and C-reactive protein (CRP) was 77.4 mg/L. Cranial ultrasound showed a lentiform 8.9 × 6.9 cm collection consistent with a large uncomplicated cephalohaematoma. If the cephalohaematoma does show signs of localised infection with possible extension, appropriate imaging with high diagnostic yield for osteomyelitis (CT or magnetic resonance imaging) is warranted with consideration given to debridement. [Extracted from the article]

How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment. It was found that voltage-gated Na+ current (INa) was stimulated, and current inactivation and deactivation were slowed in SMB-treated (30 μM) HL-1 cardiomyocytes. SMB-induced increases of INa were attenuated in cells treated with ranolazine (10 μM) or eugenol (30 μM). The current-voltage relationship of INa shifted to slightly more negative potentials in SMB-treated cells, the peak INa with an EC50 value of 18 μM increased, and the steady-state inactivation curve of INa shifted to a more positive potential. However, the tail component of the rapidly activating delayed-rectifier K+ current (IKr) was dose-dependently inhibited. Cell-attached voltage-clamp recordings in SMB-treated cells showed that the frequency of action currents and prolonged action potential were higher. In SMB-treated NSC-34 neurons, the peak INa was higher; however, neither the time to peak nor the inactivation time constant (INa) changed. Pilocarpine-induced seizures were exacerbated, and acute neuronal damage and chronic mossy fiber sprouting increased in SMB-treated rats. Western blotting showed higher expression of the sodium channel in cells after chronic SMB treatment. We conclude that SMB contributes to the sodium channel-activating mechanism through which it alters cellular excitability and excitotoxicity in wide-spectrum excitable cells. [ABSTRACT FROM AUTHOR]

Background: Children receiving immunosuppressive treatment for cancer are at high risk for invasive pneumococcal disease. The 13-valent pneumococcal conjugate vaccine (PCV13) can prevent pneumococcal disease in healthy children; however, there is an absence of literature regarding the benefit of PCV13 in immunocompromised children with cancer.Methods: A prospective, open-label cohort study recruited children between ages 1 and 18 years who were receiving active immunosuppressive therapy (AIT) or were within 12 months after completing immunosuppressive therapy (CIT). Blood samples were taken before and 4 weeks after the administration of single-dose PCV13. Serotype-specific immunoglobulin G antibody titers were measured, and titers ≥0.35 μg/mL were considered protective. Solicited side effects were recorded in a 7-day diary after vaccination.Results: Eighty-five children were recruited. At baseline, ≤50% had protective antibody titers against Streptococcus pneumoniae for 10 serotypes in the AIT group and for 8 serotypes in the CIT group. Postvaccination, ≥70% had protective antibody titers for 9 and 11 serotypes in the AIT and CIT groups, respectively. Both groups had comparable responses to PCV7 serotypes, whereas a significantly higher proportion in the CIT group achieved protective antibody titers to PCV13 serotypes. There was a low rate of serious adverse events (3.5%).Conclusions: A single-dose of PCV13 is safe and immunogenic in children diagnosed with cancer. All children who are receiving therapy for cancer should receive a single dose of PCV13 as soon as possible after diagnosis, regardless of prior PCV exposure. The current data support the recommendation for an additional dose of PCV13 after the completion of immunosuppressive therapy to provide additional protection against invasive pneumococcal disease. Cancer 2017;123:4215-4223. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Piperaquine is a bisquinoline antimalarial drug that was first synthesised in the 1960s, and used extensively in China and Indochina as prophylaxis and treatment during the next 20 years. A number of Chinese research groups documented that it was at least as effective as, and better tolerated than, chloroquine against falciparum and vivax malaria, but no pharmacokinetic characterisation was undertaken. With the development of piperaquine-resistant strains of Plasmodium falciparum and the emergence of the artemisinin derivatives, its use declined during the 1980s. However, during the next decade, piperaquine was rediscovered by Chinese scientists as one of a number of compounds suitable for combination with an artemisinin derivative. The rationale for such artemisinin combination therapies (ACTs) was to provide an inexpensive, short-course treatment regimen with a high cure rate and good tolerability that would reduce transmission and protect against the development of parasite resistance. This approach has now been endorsed by the WHO. Piperaquine-based ACT began as China-Vietnam 4 (CV4®: dihydroartemisinin [DHA], trimethoprim, piperaquine phosphate and primaquine phosphate), which was followed by CV8® (the same components as CV4 but in increased quantities), Artecom® (in which primaquine was omitted) and Artekin® or Duo-Cotecxin® (DHA and piperaquine phosphate only). Recent Indochinese studies have confirmed the excellent clinical efficacy of piperaquine-DHA combinations (28-day cure rates >95%), and have demonstrated that currently recommended regimens are not associated with significant cardiotoxicity or other adverse effects. The pharmacokinetic properties of piperaquine have also been characterised recently, revealing that it is a highly lipid-soluble drug with a large volume of distribution at steady state/bioavailability, long elimination half-life and a clearance that is markedly higher in children than in adults. The tolerability, efficacy, pharmacokinetic profile and low cost of piperaquine make it a promising partner drug for use as part of an ACT. [ABSTRACT FROM AUTHOR]

Piperaquine (PQ) is an antimalarial drug enjoying a resurgence of use in combination with an artemisinin derivative because of parasite resistance to standard treatments. Its pharmacokinetic properties have not been characterised. An assay for PQ in plasma was developed using solvent extraction and liquid chromatographic separation on a Waters XTerra™ RP18 column, with a mobile phase of 7% acetonitrile in water (containing 0.025% trifluoroacetic acid, 0.1% NaCl and 0.008% triethylamine) and UV detection at 340 nm. The assay was linear up to 1000 μg/l. Intra- and inter-day relative standard deviations were <10% (5–500 μg/l) and <21% (5–500 μg/l), respectively. Inter-day limits of quantitation and detection were 5 μg/l and 3 μg/l, respectively. A preliminary pharmacokinetic study in a patient who received 2.56 g of PQ phosphate orally with dihydroartemisinin as four doses over 32 h found an apparent steady-state volume of distribution of 447 l/kg, an apparent oral clearance 0.93 l/h/kg and a terminal half-life of 17.3 days. [Copyright &y& Elsevier]

Zileuton (Zyflo®) is regarded to be an inhibitor of 5-lipoxygenase. Although its effect on Ca2+-activated K+ currents has been reported, its overall ionic effects on neurons are uncertain. In whole-cell current recordings, zileuton increased the amplitude of Ca2+-activated K+ currents with an EC 50 of 3.2 μM in pituitary GH 3 lactotrophs. Furthermore, zileuton decreased the amplitudes of both delayed-rectifier K+ current (I K(DR)) and M-type K+ current (I K(M)). Conversely, no modification of hyperpolarization-activated cation current (I h) was demonstrated in its presence of zileuton, although the subsequent addition of cilobradine effectively suppressed the current. In inside-out current recordings, the addition of zileuton to the bath increased the probability of large-conductance Ca2+-activated K+ (BK Ca) channels; however, the subsequent addition of GAL-021 effectively reversed the stimulation of channel activity. The kinetic analyses showed an evident shortening in the slow component of mean closed time of BK Ca channels in the presence of zileuton, with minimal change in mean open time or that in the fast component of mean closed time. The elevation of BK Ca channels caused by zileuton was also observed in hippocampal mHippoE-14 neurons, without any modification of single-channel amplitude. In conclusion, except for its suppression of 5-lipoxygenase, our results indicate that zileuton does not exclusively act on BK Ca channels, and its inhibitory effects on I K(DR) and I K(M) may combine to exert strong influence on the functional activities of electrically excitable cells in vivo. [ABSTRACT FROM AUTHOR]

Highlights: [•] We investigated mechanical ventilation and developmental disorders in ELBW infants. [•] Ventilation ≥15 days was associated with a higher risk for cerebral palsy and ADHD. [•] Autism and intellectual disability were not associated with prolonged ventilation. [•] A brain-protective respiratory support strategy is required for this population. [Copyright &y& Elsevier]

Background Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood. Methods ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017–2018). Results Overall, 552 SABs were identified (incidence 4.4/100 000/year). Indigenous children, those from lower socioeconomic areas and neonates were overrepresented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay >30 days (26%), intensive care unit admission (20%), relapse (4%), or death (3%). Predictors of mortality included prematurity (adjusted odds ratio [aOR],16.8; 95% confidence interval [CI], 1.6–296.9), multifocal infection (aOR, 22.6; CI, 1.4–498.5), necrotizing pneumonia (aOR, 38.9; CI, 1.7–1754.6), multiorgan dysfunction (aOR, 26.5; CI, 4.1–268.8), and empiric vancomycin (aOR, 15.7; CI, 1.6–434.4); while infectious diseases (ID) consultation (aOR, 0.07; CI.004–.9) was protective. Neither MRSA nor vancomycin trough targets impacted survival; however, empiric vancomycin was associated with nephrotoxicity (OR, 3.1; 95% CI 1.3–8.1). Conclusions High SAB incidence was demonstrated and for the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, while ID consultation was protective. The need to reevaluate pediatric vancomycin trough targets and limit unnecessary empiric vancomycin exposure to reduce poor outcomes and nephrotoxicity is highlighted. One in 3 children experienced considerable SAB morbidity; therefore, pediatric inclusion in future SAB comparator trials is paramount to improve outcomes. [ABSTRACT FROM AUTHOR]