Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. RESULTS: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. CONCLUSIONS: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Reduction in Inpatient Central Line Associated Blood Stream Infection Post Implementation of Bundled Care Measures in Patients with Benign and Malignant Hematological Conditions in a Single Pediatric Institution

Abstract Background: Central line associated blood stream infections (CLABSIs) are a significant source of morbidity, mortality and cost for pediatric hematology/oncology patients. In response to increasing CLABSI rates, the Hematology/Oncology division at Primary Children's Hospital (PCH) initiated a quality improvement project to reduce CLABSIs in January 2011. This effort included participation in the Children's Hospital Association (CHA) quality improvement initiative targeted at reducing CLABSIs in hematology/oncology patients from 2011 through 2015, implementation of best practice central line maintenance bundles, and ongoing monitoring of staff adherence to the maintenance care bundles. Objective: The objective of this study was to study the relationship and impact of implementation of a comprehensive central line care quality improvement program on CLABSI rates and bloodstream pathogens in children admitted to our hospital with benign and malignant hematological conditions. Methods: We retrospectively identified CLABSIs in children with a hematology/oncology diagnosis admitted to the 32 bed immunocompromised unit at Primary Children's Hospital from January 2006 through July 2015. We used the National Health Safety Network and Center for Disease Control's definition for CLABSI. The pre-intervention period was from January 2006 through December 2010. The post-intervention period was from January 2011 through July 2015. We calculated CLABSI events per 1000 line days for both the pre- and post-intervention groups. In January 2011, our hospital implemented a central line quality improvement initiative, which includedCDC-based guidelines on: daily central line assessment, hand hygiene, sterile/non-sterile gloves and mask depending on procedure, specific central line site care protocols with scrub and dressing change schedule, specific hub/cap/tubing care and parental fluid/medication administration. Results: More than 75% of CLABSIs in hospitalized children with a hematology/oncology diagnosis, in both the pre- and post-intervention periods occurred in patients with benign and malignant hematological conditions. From 2006-2010, there were 156 infections [4.84/1,000 line days (32,229 line days)] documented in hospitalized hematology/oncology patients of which 123 infections were in patients with any hematological condition. This decreased to 80 infections [2.86/1,000 line days (28,003 line days)] in all hospitalized hematology/oncology patients, and to 65 in patients with any hematological conditions from 2010-2015 (Fig 1). Viridans group Streptococci was the leading cause of CLABSIs in both pre- and post-intervention periods (27% and 20%, respectively), but we observed post-intervention notable decreases among Viridans group Streptococci, coagulase-negative Staphylococci, and Candida species. Gram negative and Enterococcus spp. infections appeared to remain similar in the pre- and post-intervention period (Fig 2). Conclusion: In both pre- and post-implementation periods, patients with benign and malignant hematological conditions comprise the majority (75%) of all hematology/oncology patients who experience CLABSI events.After implementation of a central line care quality improvement initiative in 2011, CLABSI events decreased among all hematology/oncology patients, with apparent decreases noted in infections involving Viridans group Streptococci, coagulase-negative Staphylococci and Candida spp. It appears as though CLABSIs due to organisms common to the lower gastrointestinal tract, i.e. gram negative organisms and Enterococcus spp., were similar in both study periods. This may indicate that infections involving these organisms may be less amenable to reduction with current best practice central line maintenance care bundles. Continuing to evaluate these data will not only further our understanding of CLABSIs in patients with benign and malignant hematological conditions but also bloodstream infections (BSI) in general in the hematology/oncology population. This information will guide ongoing refinements of interventions to reduce BSI in this population. Figure 1. CLABSI events and annual CLABSI rate 2006-2015 Figure 1. CLABSI events and annual CLABSI rate 2006-2015 Figure 2. Causative pathogens in CLABSI events among patients with benign and malignant hematological conditions pre- and post-intervention Figure 2. Causative pathogens in CLABSI events among patients with benign and malignant hematological conditions pre- and post-intervention Disclosures No relevant conflicts of interest to declare. </jats:sec