Epidemiology and Outcomes of Children with Kidney Failure Receiving Kidney Replacement Therapy in Australia and New Zealand.

Introduction: The incidence and outcomes of kidney replacement therapy (KRT) have been well-studied in adults, but much less so in children. This study aimed to investigate the epidemiology and outcomes of KRT in children in Australia and New Zealand from 2000 to 2020. Methods: Children aged <18 years initiating KRT in Australia and New Zealand between January 1, 2000 and December 31, 2020 and reported to the Australia and New Zealand Dialysis and Transplant Registry were included. Patient survival, technique-survival, and graft survival were analyzed by Cox regression analyses. Results: Overall, 1058 children (median [interquartile range (IQR)] age 11 [5-15] years, 41% female, 66% White) were followed-up with for a median period of 12.3 years. First KRT modalities were peritoneal dialysis (PD; 48%), hemodialysis (HD; 34%), and kidney transplantation (KT; 18%). Pre-emptive KT incidence was highest in Caucasian children (80.4%) and lowest in the Indigenous population (3.2%). There was no difference in 5-year patient survival rates between 2011 and 2020 (96.9%, 95% confidence interval [CI] 93.8-98.4) and the preceding decade, 2000-2010 (94.5%, 95% CI 90.4-96.8) (P = 0.79). There was no difference in 5-year death-censored technique survival between 2011 and 2020 (51.2%, 95% CI 39.1-62) and 2000-2010 (48.8%, 95% CI 40.5-56.6) (P = 0.27). However, 5-year derath-censored graft survival was significantly higher in 2011-2020 (88.4%, 95% CI 84.6-91.4) than in 2000-2010 (84.3%, 95% CI 80.4-87.5) (P < 0.001). Conclusions: PD is the most commonly prescribed KRT modality for children in Australia and New Zealand. Patient-survival, technique-survival, and graft survival rates are excellent and graft survival has improved over the last 2 decades.

Corrigendum: PCRRT Expert Committee ICONIC position paper on prescribing kidney replacement therapy in critically sick children with acute liver failure.

[This corrects the article DOI: 10.3389/fped.2021.833205.].

Personal monitoring to reduce exposure to black carbon in children with asthma: a pilot study.

Using an advice-based intervention in a cohort of children with asthma, designed to reduce personal pollution exposure, a mean reduction in black carbon exposure of 34% was found, the primary reduction happening within the home environment https://bit.ly/301Xemt.

Clofazimine in Mycobacterium abscessus peritonitis: A pediatric case report.

Peritonitis- and catheter-related infections due to nontuberculous mycobacteria (NTM) including Mycobacterium abscessus have been reported among adults on peritoneal dialysis (PD). There is no recommended antimicrobial regimen for the treatment of M. abscessus peritonitis. Clofazimine has emerged as an important adjuvant antimicrobial treatment of M. abscessus lung infection. We report, to our knowledge, the first case of M. abscessus PD peritonitis in a child treated successfully using clofazimine as a novel adjuvant therapy to amikacin and clarithromycin. Her clinical features were similar to those of bacterial peritonitis, but she had persistence of symptoms and high inflammatory markers despite empirical therapy for peritonitis. Bacterial culture of PD effluent became positive for M. abscessus after 5 days. There was complete symptom resolution after 6 days of multidrug therapy. Due to ototoxicity, amikacin was discontinued after 6 weeks, while clarithromycin and clofazimine were continued for 9 months to ensure complete pathogen eradication before a planned renal transplant. A high index of suspicion in refractory or culture-negative cases is important for the diagnosis of NTM peritonitis. Multidrug therapy is recommended for M. abscessus infections. Clofazimine was chosen as a novel adjunct antimicrobial because of its pharmacokinetics, ease of administration, cost-effectiveness, and lack of serious adverse events.

PCRRT Expert Committee ICONIC Position Paper on Prescribing Kidney Replacement Therapy in Critically Sick Children With Acute Liver Failure.

Management of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in the pediatric population can be challenging. Kidney manifestations of liver failure, such as hepatorenal syndrome (HRS) and acute kidney injury (AKI), are increasingly prevalent and may portend a poor prognosis. The overall incidence of AKI in children with ALF has not been well-established, partially due to the difficulty of precisely estimating kidney function in these patients. The true incidence of AKI in pediatric patients may still be underestimated due to decreased creatinine production in patients with advanced liver dysfunction and those with critical conditions including shock and cardiovascular compromise with poor kidney perfusion. Current treatment for kidney dysfunction secondary to liver failure include conservative management, intravenous fluids, and kidney replacement therapy (KRT). Despite the paucity of evidence-based recommendations concerning the application of KRT in children with kidney dysfunction in the setting of ALF, expert clinical opinions have been evaluated regarding the optimal modalities and timing of KRT, dialysis/replacement solutions, blood and dialysate flow rates and dialysis dose, and anticoagulation methods.

Airway dendritic cell maturation in children exposed to air pollution.

Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 µg/m3, n = 138), middle (25.6 to 26.8 µg/m3, n = 126), and upper (26.8 to 31.0 µg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of "mature" airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.

Risk factors associated with allograft failure in pediatric kidney transplant recipients with focal segmental glomerulosclerosis.

BACKGROUND: With improved outcomes for children transplanted with FSGS since previous NAPRTCS registry reports, this study re-evaluates the association of living donation, immunosuppression, and DGF on graft survival. SETTING: Patients transplanted between 2002 and 2016, comparing FSGS diagnosis vs other glomerular diseases. METHODS: Primary outcomes were allograft survival and FSGS recurrent-free graft survival. Potential risk factors were obtained at the time of transplant and up to 30 days post-transplantation. Analysis considered a priori that DGF may be a proxy for severe FSGS recurrence. Multivariable survival models for outcome were tested for sensitivity without/with DGF to determine features independent of recurrence. RESULTS: From the larger cohort of 3010 patients, 5-year graft survival in children with FSGS (n = 455) was worse (74.3%) compared with other glomerular diseases (87.1%, n = 690) (HR 1.45, P = 0.033). Modeling all glomerular diseases, survival risk was associated with deceased donor (HR 1.83, P = 0.002), re-transplantation (HR 1.58, P = 0.013), and recipient age (HR 1.06/y, P = 0.002). The living donor advantage was not confirmed in a FSGS model (HR 1.51 for deceased, P = 0.12). DGF was highly associated with graft failure (HR 4.39, P < 0.001) and independent of re-transplant history but not FSGS diagnosis. Induction agents or primary immunosuppression choices were not associated with survival. CONCLUSION: Graft survival rates have improved since the previous report. Living donor did not predict graft failure, but there remains no survival advantage. DGF was the primary independent predictor for graft loss secondary to FSGS recurrence, consistent with DGF being a proxy for severe recurrent disease.

Protective activity of geraniol against acetic acid and Helicobacter pylori- induced gastric ulcers in rats.

Geraniol, an active constituent of rose and palmarosa essential oils, possesses several pharmacological properties, including antioxidant, antibacterial and antiulcer activity. Geraniol was therefore investigated for its antiulcer and anti-Helicobacter pylori activity in rats. Ulcers were induced by injecting acetic acid into the sub-serosal layer of the stomach followed by orogastric inoculation of H. pylori for 7 days. Geraniol (15 and 30 mg/kg), vehicle and a standard drug combination (amoxicillin, 50 mg/kg; clarithromycin, 25 mg/kg and omeprazole, 20 mg/kg) were administered twice daily for 14 days. All the parameters were measured at the end of treatment. The ulcer index was significantly (P < 0.05) lowered in geraniol and standard drug-treated rats as compared to the H. pylori control group (4.13 ±â€¯0.43). Treatment with geraniol (30 mg/kg) significantly (P < 0.01) increased the gastric pH along with a reduction in total acidity and gastric juice volume. Geraniol significantly (P < 0.05) attenuated the myeloperoxidase activity and augmented the total glutathione level in gastric mucosa. The extent of damage in the stomach was measured using a histopathological score. The score in H. pylori control, geraniol (30 mg/kg) and standard drugs was 9, 3.5 and 2.0 respectively. In the rapid urease test, treatment with geraniol (30 mg/kg) and the standard drugs produced a 33% and 67% cure respectively from H. pylori infection. Further, the reduction in bacterial load in the gastric mucosa was confirmed using modified Giemsa staining. Geraniol was observed to exhibit significant antiulcer and anti-H. pylori activity in a rodent model.

Air pollution, ethnicity and telomere length in east London schoolchildren: An observational study.

BACKGROUND: Short telomeres are associated with chronic disease and early mortality. Recent studies in adults suggest an association between telomere length and exposure to particulate matter, and that ethnicity may modify the relationship. However associations in children are unknown. OBJECTIVES: We examined associations between air pollution and telomere length in an ethnically diverse group of children exposed to high levels of traffic derived pollutants, particularly diesel exhaust, and to environmental tobacco smoke. METHODS: Oral DNA from 333 children (8-9years) participating in a study on air quality and respiratory health in 23 inner city London schools was analysed for relative telomere length using monochrome multiplex qPCR. Annual, weekly and daily exposures to nitrogen oxides and particulate matter were obtained from urban dispersion models (2008-10) and tobacco smoke by urinary cotinine. Ethnicity was assessed by self-report and continental ancestry by analysis of 28 random genomic markers. We used linear mixed effects models to examine associations with telomere length. RESULTS: Telomere length increased with increasing annual exposure to NOx (model coefficient 0.003, [0.001, 0.005], p<0.001), NO2 (0.009 [0.004, 0.015], p<0.001), PM2.5 (0.041, [0.020, 0.063], p<0.001) and PM10 (0.096, [0.044, 0.149], p<0.001). There was no association with environmental tobacco smoke. Telomere length was increased in children reporting black ethnicity (22% [95% CI 10%, 36%], p<0.001) CONCLUSIONS: Pollution exposure is associated with longer telomeres in children and genetic ancestry is an important determinant of telomere length. Further studies should investigate both short and long-term associations between pollutant exposure and telomeres in childhood and assess underlying mechanisms.

Peer support groups, mobile phones and refugee women in Melbourne.

In this article, we discuss qualitative findings basing on the experiences of refugee women living in Melbourne, Australia, who participated in a peer support training programme and received a free mobile phone. We pay attention to social support as a health enhancing strategy and empowerment that occurred among the participants. Participation in peer support groups and access to a mobile phone were beneficial for the women. Peer support functioned as social support among group members. The programme allowed the women to be connected to their families and the wider communities and assisted them to access health care and other settlement aspects with greater ease. It also increased personal empowerment among the women. Our programme shows that by tapping on community resources to ameliorate personal or resettlement issues, the burden on service providers can be reduced. Our findings also offer a model for future research and programmes regarding refugee people elsewhere.

Social connectedness and mobile phone use among refugee women in Australia.

The aim of this research was to inform the development of mobile phone-assisted health promotion programmes that support social connectedness among refuge women to enhance their mental, physical and social health. For refugees, relationship development during the early stages of resettlement is often difficult. Enhancing personal skills, and resources, can enhance relationships that provide social support. It can also contribute to the development of social relationships in communities and thence acculturation. Communication technologies can assist refugees, if their particular needs and capacities are taken into account. This paper reports a study of refugee women's experience of an intervention based on principles of empowerment and using peer support training and the provision of free mobile phones, and free calls, for at least 1 year. Potential participants were invited by the Afghan, Burmese and Sudanese community leaders to an information session, where the study was explained and invitations to participate extended. A snowball sampling technique was also used, where the first group of participants invited people they had relationships with to join the programme. One hundred and eleven participants were recruited from the three groups. All were from refugee backgrounds. Data collection consisted of: a pre- and post-intervention questionnaire; a log of outgoing phone calls; and in-depth interviews with a subgroup of the study population. The call logs described the patterns of interpersonal relationships facilitated by the mobile phones. In the interviews, characteristics of interpersonal social support, and relationships with heritage and host communities, were described. The quantitative data were analysed using descriptive statistics and the qualitative data using thematic analysis. By describing the conditions under which mobile phone technology can enhance interpersonal and community connectedness, we strengthen the evidence base for the use of mobile phone technology in health promotion programmes with refugee groups.

Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial.

BACKGROUND: The effectiveness of intermittent montelukast for wheeze in young children is unclear. We aimed to assess whether intermittent montelukast is better than placebo for treatment of wheeze in this age group. Because copy numbers of the Sp1-binding motif in the arachidonate 5-lipoxygenase (ALOX5) gene promoter (either 5/5, 5/x, or x/x, where x does not equal 5) modifies response to montelukast in adults, we stratified by this genotype. METHODS: We did this multicentre, parallel-group, randomised, placebo-controlled trial between Oct 1, 2010, and Dec 20, 2013, at 21 primary care sites and 41 secondary care sites in England and Scotland. Children aged 10 months to 5 years with two or more wheeze episodes were allocated to either a 5/5 or 5/x+x/x ALOX5 promoter genotype stratum, then randomly assigned (1:1) via a permuted block schedule (size ten), to receive intermittent montelukast or placebo given by parents at each wheeze episode over a 12 month period. Clinical investigators and parents were masked to treatment group and genotype strata. The primary outcome was number of unscheduled medical attendances for wheezing episodes. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01142505. FINDINGS: We randomly assigned 1358 children to receive montelukast (n=669) or placebo (n=677). Consent was withdrawn for 12 (1%) children. Primary outcome data were available for 1308 (96%) children. There was no difference in unscheduled medical attendances for wheezing episodes between children in the montelukast and placebo groups (mean 2·0 [SD 2·6] vs 2·3 [2·7]; incidence rate ratio [IRR] 0·88, 95% CI: 0·77-1·01; p=0·06). Compared with placebo, unscheduled medical attendances for wheezing episodes were reduced in children given montelukast in the 5/5 stratum (2·0 [2·7] vs 2·4 [3·0]; IRR 0·80, 95% CI 0·68-0·95; p=0·01), but not in those in the 5/x+x/x stratum (2·0 [2·5] vs 2·0 [2·3]; 1·03, 0·83-1·29; p=0·79, pinteraction=0·08). We recorded one serious adverse event, which was a skin reaction in a child allocated to placebo. INTERPRETATION: Our findings show no clear benefit of intermittent montelukast in young children with wheeze. However, the 5/5 ALOX5 promoter genotype might identify a montelukast-responsive subgroup. FUNDING: Medical Research Council (UK) and National Institute for Health Research.

Carbon in airway macrophages from children with asthma.

BACKGROUND: Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. METHODS: AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (µm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. RESULTS: AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). CONCLUSIONS: Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.

What makes a hospital manager competent at the middle and senior levels?

OBJECTIVE: The purpose of this paper is to confirm the core competencies required for middle to senior level managers in Victorian public hospitals in both metropolitan and regional/rural areas. METHODS: This exploratory mixed-methods study used a three-step approach which included position description content analysis, focus group discussions and online competency verification and identification survey. RESULTS: The study validated a number of key tasks required for senior and middle level hospital managers (levels II, III and IV) and identified and confirmed the essential competencies for completing these key tasks effectively. As a result, six core competencies have been confirmed as common to the II, III and IV management levels in both the Melbourne metropolitan and regional/rural areas. CONCLUSIONS: Six core competencies are required for middle to senior level managers in public hospitals which provide guidance to the further development of the competency-based educational approach for training the current management workforce and preparing future health service managers. With the detailed descriptions of the six core competencies, healthcare organisations and training institutions will be able to assess the competency gaps and managerial training needs of current health service managers and develop training programs accordingly.

Competency requirements for middle and senior managers in community health services.

The Australian health system has been subjected to rapid changes in the last 20 years to meet increasingly unmet health needs. Improvement of the efficiency and comprehensiveness of community-based services is one of the solutions to reducing the increasing demand for hospital care. Competent managers are one of the key contributors to effective and efficient health service delivery. However, the understanding of what makes a competent manager, especially in the community health services (CHS), is limited. Using an exploratory and mixed-methods approach, including focus group discussions and an online survey, this study identified five key competencies required by senior and mid-level CHS managers in metropolitan, regional and rural areas of Victoria: Interpersonal, communication qualities and relationship management; Operations, administration and resource management; Knowledge of the health care environment; Leading and managing change; and Evidence-informed decision-making. This study confirms that core competencies do exist across different management levels and improves our understanding of managerial competency requirements for middle to senior CHS managers, with implications for current and future health service management workforce development.

Constant connections: piloting a mobile phone-based peer support program for Nuer (southern Sudanese) women.

Refugee women have poor psychosocial health as a result of past trauma and difficulties associated with settlement. This study was a pilot to find out how to use mobile phone-based peer support to improve the psychosocial health of, and facilitate settlement in a group of nine Nuer refugee women in Melbourne, Australia. Nine participants recruited by a community leader received peer support training over two five-week periods. They were further provided with mobile phone recharge vouchers to call one another to practice peer support techniques. The fifth and final sessions were focus groups to evaluate the intervention. Notes from the focus groups were thematically analysed. The women reported greater confidence and empowerment as they received more support, had better connections within the group and better access to information. Relationships with friends, family and the community became richer as they adopted and experienced more functional communication patterns. Using mobile phones for peer support helped to re-create community by bridging the geographical distance that separates refugee women. It allowed the women, from similar backgrounds and with similar experiences, to provide mutual support and exchange information through a verbal channel, the form of communication they are most comfortable with. The program demonstrates the positive psychosocial effect of peer support in a refugee community, and provides a viable model for using mobile phones in health promotion interventions. The successful outcomes, as perceived by the participants, are indicative of the potential of using technology to bridge health inequities in a marginalised group.

Cigarette smoke and platelet-activating factor receptor dependent adhesion of Streptococcus pneumoniae to lower airway cells.

BACKGROUND: Exposure to cigarette smoke (CS) is associated with increased risk of pneumococcal infection. The mechanism for this association is unknown. We recently reported that the particulate matter from urban air simulates platelet-activating factor receptor (PAFR)-dependent adhesion of pneumococci to airway cells. We therefore sought to determine whether CS stimulates pneumococcal adhesion to airway cells. METHODS: Human alveolar (A549), bronchial (BEAS2-B), and primary bronchial epithelial cells (HBEpC) were exposed to CS extract (CSE), and adhesion of Streptococcus pneumoniae determined. The role of PAFR in mediating adhesion was determined using a blocker (CV-3988). PAFR transcript level was assessed by quantitative real-time PCR, and PAFR expression by flow cytometry. Lung PAFR transcript level was assessed in mice exposed to CS, and bronchial epithelial PAFR expression assessed in active-smokers by immunostaining. RESULTS: In A549 cells, CSE 1% increased pneumococcal adhesion (p<0.05 vs control), PAFR transcript level (p<0.01), and PAFR expression (p<0.01). Pneumococcal adhesion to A549 cells was attenuated by CV-3988 (p<0.001). CSE 1% stimulated pneumococcal adhesion to BEAS2-B cells and HBEpC (p<0.01 vs control). CSE 1% increased PAFR expression in BEAS2-B (p<0.01), and in HBEpC (p<0.05). Lung PAFR transcript level was increased in mice exposed to CS in vivo (p<0.05 vs room air). Active smokers (n=16) had an increased percentage of bronchial epithelium with PAFR-positive cells (p<0.05 vs never smokers, n=11). CONCLUSION: CSE stimulates PAFR-dependent pneumococcal adhesion to lower airway epithelial cells. We found evidence that CS increases bronchial PAFR in vivo.

Performance of an ultra-compact biofilm reactor treating domestic and synthetic wastewaters.

The performance of an ultra-compact biofilm reactor (UCBR) treating domestic wastewater (DWW) collected from a local water reclamation plant; and gradually shifting to a mono-type carbon source synthetic wastewater (SWW) combined with DDW (CWW) and finally SWW; was investigated in this study. The total COD concentrations of influent DWW and CWW/SWW were 413.6 ± 80.8 mg/L and 454.9 ± 51.3 mg/L, respectively. The UCBR was able to achieve average total COD removal efficiencies of 70 ± 10% and 80 ± 4% for DWW and SWW respectively. The total COD concentrations of the effluent of DWW and CWW/SWW were 122.5 ± 44.4 mg/L and 89.7 ± 10.3 mg/L, respectively. These observations suggested that heterotrophs in the UCBR system were able to better assimilate and remove carbon of mono-type SWW compared to diverse carbon sources such as DWW; although the influent soluble COD concentrations of the SWW were higher than those of the DWW. However, the effluent NH(4)(+)-N concentrations for both types of wastewater were rather similar, <3.0 mg/L; although the influent NH(4)(+)-N concentrations of the DWW were 1.5 times those of the SWW.