Predicting the causative pathogen among children with pneumonia using a causal Bayesian network.

BACKGROUND: Pneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incorporating both domain expert knowledge and numerical data. METHODS: We used domain expert knowledge and data in combination and iteratively, to construct, parameterise and validate a causal BN to predict causative pathogens for childhood pneumonia. Expert knowledge elicitation occurred through a series of group workshops, surveys and one-on-one meetings involving 6-8 experts from diverse domain areas. The model performance was evaluated based on both quantitative metrics and qualitative expert validation. Sensitivity analyses were conducted to investigate how the target output is influenced by varying key assumptions of a particularly high degree of uncertainty around data or domain expert knowledge. RESULTS: Designed to apply to a cohort of children with X-ray confirmed pneumonia who presented to a tertiary paediatric hospital in Australia, the resulting BN offers explainable and quantitative predictions on a range of variables of interest, including the diagnosis of bacterial pneumonia, detection of respiratory pathogens in the nasopharynx, and the clinical phenotype of a pneumonia episode. Satisfactory numeric performance has been achieved including an area under the receiver operating characteristic curve of 0.8 in predicting clinically-confirmed bacterial pneumonia with sensitivity 88% and specificity 66% given certain input scenarios (i.e., information that is available and entered into the model) and trade-off preferences (i.e., relative weightings of the consequences of false positive versus false negative predictions). We specifically highlight that a desirable model output threshold for practical use is very dependent upon different input scenarios and trade-off preferences. Three commonly encountered scenarios were presented to demonstrate the potential usefulness of the BN outputs in various clinical pictures. CONCLUSIONS: To our knowledge, this is the first causal model developed to help determine the causative pathogen for paediatric pneumonia. We have shown how the method works and how it would help decision making on the use of antibiotics, providing insight into how computational model predictions may be translated to actionable decisions in practice. We discussed key next steps including external validation, adaptation and implementation. Our model framework and the methodological approach can be adapted beyond our context to broad respiratory infections and geographical and healthcare settings.

Detrimental impact of early biopsy-proven rejection in liver transplantation.

Existing literature offers conflicting conclusions about whether early acute cellular rejection influences long-term outcomes in liver transplantation. We retrospectively collected donor and recipient data on all adult, first-time liver transplants performed at a single center between 2008 and 2020. We divided this population into two cohorts based on the presence of early biopsy-proven acute cellular rejection (EBPR) within the first 90 days post-transplant and compared outcomes between the groups. There were 896 liver transplants that met inclusion criteria with 112 cases (12.5%) of EBPR. Recipients who developed EBPR had higher biochemical Model for End-Stage Liver Disease scores (28 vs. 24, p < .01), but other donor and recipient characteristics were similar. Recipients with EBPR had similar overall survival compared to patients without EBPR (p = .09) but had decreased graft survival (p < .05). EBPR was also associated with decreased time to first episode of late (> 90 days post-transplant) rejection (p < .0001) and increased vulnerability to bacterial and viral infection (p < .05). In subgroup analysis of recipients with autoimmune indications for liver transplantation, EBPR had a more pronounced association with patient death (hazard ratio [HR] 3.9, p < .05) and graft loss (HR 4.0, p < .01). EBPR after liver transplant is associated with inferior graft survival, increased susceptibility to late rejections, and increased vulnerability to infection.

Development of a capillary zone electrophoresis method to monitor magnesium ion consumption during in vitro transcription for mRNA production.

Messenger RNA (mRNA) vaccines represent a landmark in vaccinology, especially with their success in COVID-19 vaccines, which have shown great promise for future vaccine development and disease prevention. As a platform technology, synthetic mRNA can be produced with high fidelity using in vitro transcription (IVT). Magnesium plays a vital role in the IVT process, facilitating the phosphodiester bond formation between adjacent nucleotides and ensuring accurate transcription to produce high-quality mRNA. The development of the IVT process has prompted key inquiries about in-process characterization of magnesium ion (Mg++) consumption, relating to the RNA polymerase (RNAP) activation, fed-batch mode production yield, and mRNA quality. Hence, it becomes crucial to monitor the free Mg++ concentration throughout the IVT process. However, no free Mg++ analysis method has been reported for complex IVT reactions. Here we report a robust capillary zone electrophoresis (CZE) method with indirect UV detection. The assay allows accurate quantitation of free Mg++ for the complex IVT reaction where it is essential to preserve IVT samples in their native-like state during analysis to avoid dissociation of bound Mg complexes. By applying this CZE method, the relationships between free Mg++ concentration, the mRNA yield, and dsRNA impurity level were investigated. Such mechanistic understanding facilitates informed decisions regarding the quantity and timing of feeding starting materials to increase the yield. Furthermore, this approach can serve as a platform method for analyzing the free Mg++ in complex sample matrices where preserving the native-like state of Mg++ binding is key for accurate quantitation.

Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial.

BACKGROUND: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates TNF α production that amplifies allograft inflammation and may negatively affect transplant outcomes. METHODS: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase 2 clinical trial. A total of 225 primary transplant recipients of deceased-donor kidneys (KTx; 38.2% Black/African American, 44% White) were randomized to receive intravenous infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated before kidney reperfusion. All patients received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary end point was the difference between groups in mean 24-month eGFR. RESULTS: There was no difference in the primary end point of 24-month eGFR between IFX (52.45 ml/min per 1.73 m 2 ; 95% CI, 48.38 to 56.52) versus PLBO (57.35 ml/min per 1.73 m 2 ; 95% CI, 53.18 to 61.52; P =0.1). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ, and day 7 post-KTx plasma analyses showed approximately ten-fold lower TNF ( P <0.001) in IFX versus PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) versus PLBO (13.4%; P =0.004), with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) versus PLBO (4.9%; P =0.06). CONCLUSIONS: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peritransplant inflammation as a strategy to improve KTx outcomes.Clinical Trial registry name and registration number:clinicaltrials.gov (NCT02495077).

Pediatric Injury Transfer Patterns During the COVID-19 Pandemic: An Interrupted time Series Analysis.

INTRODUCTION: With the expected surge of adult patients with COVID-19, the Children's Hospital Association recommended a tiered approach to divert children to pediatric centers. Our objective was understanding changes in interfacility transfer to Pediatric Trauma Centers (PTCs) during the first 6 mo of the pandemic. METHODS: Children aged < 18 y injured between January 1, 2016 and September 30, 2020, who met National Trauma Databank inclusion criteria from 9 PTCs were included. An interrupted time-series analysis was used to estimate an expected number of transferred patients compared to observed volume. The "COVID" cohort was compared to a historical cohort (historical average [HA]), using an average across 2016-2019. Site-based differences in transfer volume, demographics, injury characteristics, and hospital-based outcomes were compared between cohorts. RESULTS: Twenty seven thousand thirty one/47,382 injured patients (57.05%) were transferred to a participating PTC during the study period. Of the COVID cohort, 65.4% (4620/7067) were transferred, compared to 55.7% (3281/5888) of the HA (P < 0.001). There was a decrease in 15-y-old to 17-y-old patients (10.43% COVID versus 12.64% HA, P = 0.003). More patients in the COVID cohort had injury severity scores ≤ 15 (93.25% COVID versus 87.63% HA, P < 0.001). More patients were discharged home after transfer (31.80% COVID versus 21.83% HA, P < 0.001). CONCLUSIONS: Transferred trauma patients to Level I PTC increased during the COVID-19 pandemic. The proportion of transferred patients discharged from emergency departments increased. Pediatric trauma transfers may be a surrogate for referring emergency department capacity and resources and a measure of pediatric trauma triage capability.

Evaluating the Regional Differences in Pediatric Injury Patterns During the COVID-19 Pandemic.

INTRODUCTION: Reports of pediatric injury patterns during the COVID-19 pandemic are conflicting and lack the granularity to explore differences across regions. We hypothesized there would be considerable variation in injury patterns across pediatric trauma centers in the United States. MATERIALS AND METHODS: A multicenter, retrospective study evaluating patients <18 y old with traumatic injuries meeting National Trauma Data Bank criteria was performed. Patients injured after stay-at-home orders through September 2020 ("COVID" cohort) were compared to "Historical" controls from an averaged period of equivalent dates in 2016-2019. Differences in injury type, intent, and mechanism were explored at the site level. RESULTS: 47,385 pediatric trauma patients were included. Overall trauma volume increased during the COVID cohort compared to the Historical (COVID 7068 patients versus Historical 5891 patients); however, some sites demonstrated a decrease in overall trauma of 25% while others had an increase of over 33%. Bicycle injuries increased at every site, with a range in percent change from 24% to 135% increase. Although the greatest net increase was due to blunt injuries, there was a greater relative increase in penetrating injuries at 7/9 sites, with a range in percent change from a 110% increase to a 69% decrease. CONCLUSIONS: There was considerable discrepancy in pediatric injury patterns at the individual site level, perhaps suggesting a variable impact of the specific sociopolitical climate and pandemic policies of each catchment area. Investigation of the unique response of the community during times of stress at pediatric trauma centers is warranted to be better prepared for future environmental stressors.

Modeling COVID-19 disease processes by remote elicitation of causal Bayesian networks from medical experts.

BACKGROUND: COVID-19 is a new multi-organ disease causing considerable worldwide morbidity and mortality. While many recognized pathophysiological mechanisms are involved, their exact causal relationships remain opaque. Better understanding is needed for predicting their progression, targeting therapeutic approaches, and improving patient outcomes. While many mathematical causal models describe COVID-19 epidemiology, none have described its pathophysiology. METHODS: In early 2020, we began developing such causal models. The SARS-CoV-2 virus's rapid and extensive spread made this particularly difficult: no large patient datasets were publicly available; the medical literature was flooded with sometimes conflicting pre-review reports; and clinicians in many countries had little time for academic consultations. We used Bayesian network (BN) models, which provide powerful calculation tools and directed acyclic graphs (DAGs) as comprehensible causal maps. Hence, they can incorporate both expert opinion and numerical data, and produce explainable, updatable results. To obtain the DAGs, we used extensive expert elicitation (exploiting Australia's exceptionally low COVID-19 burden) in structured online sessions. Groups of clinical and other specialists were enlisted to filter, interpret and discuss the literature and develop a current consensus. We encouraged inclusion of theoretically salient latent (unobservable) variables, likely mechanisms by extrapolation from other diseases, and documented supporting literature while noting controversies. Our method was iterative and incremental: systematically refining and validating the group output using one-on-one follow-up meetings with original and new experts. 35 experts contributed 126 hours face-to-face, and could review our products. RESULTS: We present two key models, for the initial infection of the respiratory tract and the possible progression to complications, as causal DAGs and BNs with corresponding verbal descriptions, dictionaries and sources. These are the first published causal models of COVID-19 pathophysiology. CONCLUSIONS: Our method demonstrates an improved procedure for developing BNs via expert elicitation, which other teams can implement to model emergent complex phenomena. Our results have three anticipated applications: (i) freely disseminating updatable expert knowledge; (ii) guiding design and analysis of observational and clinical studies; (iii) developing and validating automated tools for causal reasoning and decision support. We are developing such tools for the initial diagnosis, resource management, and prognosis of COVID-19, parameterized using the ISARIC and LEOSS databases.

Unusual local epidemic of paediatric respiratory syncytial virus during a time of global pandemic.

BACKGROUND: Western Australia (WA) public health measures to eradicate SARS-CoV-2 resulted in a secondary reduction in paediatric respiratory syncytial virus (RSV) admissions. Following an absent expected 2020 winter peak, RSV-positive admissions surged during the summer of 2020. AIM: This report examines the number of RSV-positive admissions and severities across 36 months to better understand this out-of-season epidemic. METHODS: A retrospective observational study was performed assessing the number and severity of RSV-related respiratory hospitalisations at a peripheral paediatric centre from March 2018 to February 2021. Data were extracted from the hospital clinical database. RESULTS: The total number of included participants was n = 294. The total number of RSV hospitalisations in SY (study year) 2018 (March 2018 to February 2019), SY 2019 (March 2019 to February 2020) and SY 2020 (March 2020 to February 2021) was 67, 98 and 129, respectively. Prior to SARS-CoV-2, RSV hospitalisations were highest during the winter months. In SY 2020, there were 0 RSV hospitalisations during winter, while 101 admissions in the following summer season. The proportion of admissions requiring respiratory support was significantly reduced in SY 2020 (34.1%) compared to SY 2018 (46.9%, P = 0.050) and SY 2019 (55.2%, P = 0.004). The median length of stay (LOS) in 2020 was 2.0 which was significantly reduced from 2018 and 2019 which was 3.0, P = 0.001; and 3.0, P < 0.001, respectively. CONCLUSION: Following a period of RSV absence, there was an unprecedented surge in admission, however, with lower severity and shorter LOS.

A surge in human metapneumovirus paediatric respiratory admissions in Western Australia following the reduction of SARS-CoV-2 non-pharmaceutical interventions.

AIM: Western Australian laboratory data demonstrated a decrease in human metapneumovirus (hMPV) detections through 2020 associated with SARS-CoV-2-related non-pharmaceutical interventions (NPIs), followed by a subsequent surge in metropolitan region in mid-2021. We aimed to assess the impact of the surge in hMPV on paediatric hospital admissions and the contribution of changes in testing. METHODS: All respiratory-coded admissions of children aged <16 years at a tertiary paediatric centre between 2017 and 2021 were matched with respiratory virus testing data. Patients were grouped by age at presentation and by ICD-10 AM codes into bronchiolitis, other acute lower respiratory infection (OALRI), wheeze and upper respiratory tract infection (URTI). For analysis, 2017-2019 was utilised as a baseline period. RESULTS: hMPV-positive admissions in 2021 were more than 2.8 times baseline. The largest increase in incidence was observed in the 1-4 years group (incidence rate ratio (IRR) 3.8; 95% confidence interval (CI): 2.5-5.9) and in OALRI clinical phenotype (IRR 2.8; 95% CI: 1.8-4.2). The proportion of respiratory-coded admissions tested for hMPV in 2021 doubled (32-66.2%, P < 0.001), with the greatest increase in wheeze (12-75% in 2021, P < 0.001). hMPV test percentage positivity in 2021 was higher than in the baseline period (7.6% vs. 10.1% in 2021, P = 0.004). CONCLUSION: The absence and subsequent surge underline the susceptibility of hMPV to NPIs. Increased hMPV-positive admissions in 2021 can be partially attributable to testing, but test-positivity remained high, consistent with a genuine increase. Continued comprehensive testing will help ascertain true burden of hMPV respiratory diseases.

Cross-decoration of dendritic cells by non-inherited maternal antigen-containing extracellular vesicles: Potential mechanism for PD-L1-based tolerance in cord blood and organ transplantation.

Exposure to non-inherited maternal antigens (NIMA) during the fetal period induces lifelong split tolerance to grafts expressing these allo-antigens. In adult mice, the production of extracellular vesicles (EVs) from maternal microchimeric cells causes cross-decoration (XD) of offspring dendritic cells (DC) with NIMA and upregulation of PD-L1, contributing to NIMA tolerance. To see how this may apply to humans, we tested NIMA acquisition by fetal DCS in human cord blood. The average percentage of NIMA-XD among total DCs was 2.6% for myeloid and 4.5% for Plasmacytoid DC. These cells showed higher PD-L1 expression than their non-XD counterparts (mDC: p = .0016; pDC: p = .024). We detected CD9+ EVs bearing NIMA and PD-L1 in cord blood. To determine if this immune regulatory mechanism persists beyond the pregnancy, we analyzed NIMA-expressing kidney and liver transplant recipients. We found donor antigen XD DCs in peripheral blood and graft-infiltrating DCs. As in cord blood, the pattern of donor antigen expression was punctate, and PD-L1 expression was upregulated, likely due to both protein and miRNA acquired from EV. Our findings support a mechanism for split tolerance to NIMAs that develops during pregnancy and is recapitulated in adult transplant recipients.

Liver Transplantation as a New Standard of Care in Patients With Perihilar Cholangiocarcinoma? Results From an International Benchmark Study.

OBJECTIVE: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. BACKGROUND: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. METHODS: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. RESULTS: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001). CONCLUSION: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

Use of preprocurement biopsy in donation after circulatory death liver transplantation.

We perform routine preprocurement image-guided percutaneous liver biopsies on potential donation after circulatory death (DCD) liver donors. The purpose of this study was to examine the impact of preprocurement liver biopsy on the use of livers from DCD donors. We retrospectively reviewed demographics, liver histology, and disposition of DCD liver donors within a single organ procurement organization (OPO) who underwent preprocurement liver biopsy from January 2000 through December 2019. A total of 212 potential donors underwent prerecovery biopsy. No donors were lost as a result of complications of biopsy. Of these, 183 (86.3%) had acceptable biopsies: 146 (79.8%) were successfully transplanted and 37 (20.2%) were deemed not suitable for transplant. In contrast, of 120 DCD livers recovered with the intent to transplant that were not biopsied prior to recovery, 59 (49.2%) were successfully transplanted, and 61 (50.8%) were deemed not suitable for transplant. A total of 14 donors were ruled out for transplant based on prerecovery histology. Successfully transplanted livers that underwent preprocurement biopsy were more likely to come from donors aged older than 50 years or with body mass index more than 30 kg/m2 compared with successfully transplanted livers without a prerecovery biopsy. Biopsy excluded 6.6% of DCD donor livers for transplant prior to recovery and facilitated the successful recovery and transplant of two-thirds of potential DCD donor livers. Livers intended for transplant at the time of recovery that did not undergo preprocurement biopsy were more likely to not be recovered or to be discarded. Preprocurement biopsy provides additional histologic information prior to deploying resources and helps to identify usable livers that might otherwise be declined for transplant. Consideration of liver biopsy in this group benefits OPOs and transplant centers by maximizing organ use and optimizing resource deployment.

Surgical complications after living and deceased donor liver transplant: The NSQIP transplant experience.

This study used the prospective National Surgical Quality Improvement Program (NSQIP) Transplant pilot database to analyze surgical complications after liver transplantation (LT) in LT recipients from 2017to 2019. The primary outcome was surgical complication requiring intervention (Clavien-Dindo grade II or greater) within 90 days of transplant. Of the 1684 deceased donor and 109 living donor LT cases included from 29 centers, 38% of deceased donor liver recipients and 47% of living donor liver recipients experienced a complication. The most common complications included biliary complications (19% DDLT; 31% LDLT), hemorrhage requiring reoperation (14% DDLT; 9% LDLT), and vascular complications (6% DDLT; 9% LDLT). Management of biliary leaks (35.3% ERCP, 38.0% percutaneous drainage, 26.3% reoperation) and vascular complications (36.2% angioplasty/stenting, 31.2% medication, 29.8% reoperation) was variable. Biliary (aHR 5.14, 95% CI 2.69-9.8, P < .001), hemorrhage (aHR 2.54, 95% CI 1.13-5.7, P = .024) and vascular (aHR 2.88, 95% CI .85-9.7, P = .089) complication status at 30-days post-transplant were associated with lower 1-year patient survival. We conclude that biliary, hemorrhagic and vascular complications continue to be significant sources of morbidity and mortality for LT recipients. Understanding the different risk factors for complications between deceased and living donor liver recipients and standardizing complication management represent avenues for continued improvement.

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis.

PURPOSE: To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant. MATERIALS AND METHODS: This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques. RESULTS: Among the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5-18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients. CONCLUSIONS: MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.

Urinary tract infections in children: building a causal model-based decision support tool for diagnosis with domain knowledge and prospective data.

BACKGROUND: Diagnosing urinary tract infections (UTIs) in children in the emergency department (ED) is challenging due to the variable clinical presentations and difficulties in obtaining a urine sample free from contamination. Clinicians need to weigh a range of observations to make timely diagnostic and management decisions, a difficult task to achieve without support due to the complex interactions among relevant factors. Directed acyclic graphs (DAG) and causal Bayesian networks (BN) offer a way to explicitly outline the underlying disease, contamination and diagnostic processes, and to further make quantitative inference on the event of interest thus serving as a tool for decision support. METHODS: We prospectively collected data on children present to ED with suspected UTIs. Through knowledge elicitation workshops and one-on-one meetings, a DAG was co-developed with clinical domain experts (the Expert DAG) to describe the causal relationships among variables relevant to paediatric UTIs. The Expert DAG was combined with prospective data and further domain knowledge to inform the development of an application-oriented BN (the Applied BN), designed to support the diagnosis of UTI. We assessed the performance of the Applied BN using quantitative and qualitative methods. RESULTS: We summarised patient background, clinical and laboratory characteristics of 431 episodes of suspected UTIs enrolled from May 2019 to November 2020. The Expert DAG was presented with a narrative description, elucidating how infection, specimen contamination and management pathways causally interact to form the complex picture of paediatric UTIs. Parameterised using prospective data and expert-elicited parameters, the Applied BN achieved an excellent and stable performance in predicting Escherichia coli culture results, with a mean area under the receiver operating characteristic curve of 0.86 and a mean log loss of 0.48 based on 10-fold cross-validation. The BN predictions were reviewed via a validation workshop, and we illustrate how they can be presented for decision support using three hypothetical clinical scenarios. CONCLUSION: Causal BNs created from both expert knowledge and data can integrate case-specific information to provide individual decision support during the diagnosis of paediatric UTIs in ED. The model aids the interpretation of culture results and the diagnosis of UTIs, promising the prospect of improved patient care and judicious use of antibiotics.

Assessing the utility of routine viral surveillance performed in children undergoing autologous stem cell transplantation at a single centre.

We assessed the utility of routine viral surveillance for cytomegalovirus, Epstein-Barr virus and human adenovirus in children <16 years, undergoing autologous stem cell transplantation (ASCT) at a single centre over a 10-year period. A total of 85 ASCT were performed in 65 patients. Routine viral surveillance resulted in a high number of tests performed (median 20 tests per ASCT), without any clinically significant viral detections. These data support the limited clinical utility of routine viral surveillance in children undergoing ASCT. Adopting a clinically driven approach for viral testing is likely to be both cost-effective and safe.

Infectious complications and optimising infection prevention for children with cochlear implants.

AIM: To describe the clinical epidemiology of children receiving cochlear implants, as well as the management and outcomes of cochlear implant infections and adherence to infection prevention measures. METHODS: A retrospective observational study was conducted in children ≤18 years who received cochlear implants in Western Australia's tertiary paediatric hospital. Information was obtained from medical and laboratory records regarding demographics, indication for implant, implant infection and preoperative Staphylococcus aureus screening/decolonisation. Immunisation history was examined using the Australian Immunisation Register. RESULTS: Overall, 118 children received cochlear implants, with 158 devices inserted (599 cochlear implant insertion-years). An implant infection rate of 3.8% (6/158) was identified during the study period (four pneumococcal and two community-acquired methicillin resistant S. aureus infections). All required surgical management, with an overall median duration of antibiotic therapy of 37 days (interquartile range (IQR) 29-48) and median length of stay of 8 days (IQR 8-9.5). All devices were retained and there were no relapses or deaths. Half of the children who developed cochlear implant infections (50%, 3/6) were up-to-date with additional pneumococcal vaccinations and no children (0%, 0/118) received S. aureus screening/decolonisation before implant insertion. CONCLUSIONS: Favourable outcomes were achieved with cochlear implant retention; however, the treatment was burdensome for families. We demonstrate significant scope to improve adherence to existing infection prevention strategies and provide direction for optimising preventative measures in the future. These include ensuring parental education, additional pneumococcal vaccinations and S. aureus decolonisation which are delivered as an infection prevention bundle to the growing population of infants receiving cochlear implants.

Impact of Coronavirus Disease 2019 Public Health Measures on Detections of Influenza and Respiratory Syncytial Virus in Children During the 2020 Australian Winter.

Public health measures targeting coronavirus disease 2019 have potential to impact transmission of other respiratory viruses. We found 98.0% and 99.4% reductions in respiratory syncytial virus and influenza detections, respectively, in Western Australian children through winter 2020 despite schools reopening. Border closures have likely been important in limiting external introductions.

Risk factors and outcomes for delayed kidney graft function in simultaneous heart and kidney transplant recipients: A UNOS/OPTN database analysis.

There are no prior studies assessing the risk factors and outcomes for kidney delayed graft function (K-DGF) in simultaneous heart and kidney (SHK) transplant recipients. Using the OPTN/UNOS database, we sought to identify risk factors associated with the development of K-DGF in this unique population, as well as outcomes associated with K-DGF. A total of 1161 SHK transplanted between 1998 and 2018 were included in the analysis, of which 311 (27%) were in the K-DGF (+) group and 850 in the K-DGF (-) group. In the multivariable analysis, history of pretransplant dialysis (OR: 3.95; 95% CI: 2.94 to 5.29; p < .001) was significantly associated with the development of K-DGF, as was donor death from cerebrovascular accident and longer cold ischemia time of either organ. SHK recipients with K-DGF had increased mortality (HR: 1.99; 95% CI: 1.52 to 2.60; p < .001) and death censored kidney graft failure (HR: 3.51; 95% CI: 2.29 to 5.36; p < .001) in the multivariable analysis. Similar outcomes were obtained when limiting our study to 2008-2018. Similar to kidney-only recipients, K-DGF in SHK recipients is associated with worse outcomes. Careful matching of recipients and donors, as well as peri-operative management, may help reduce the risk of K-DGF and the associated detrimental effects.