The Impact of Biologic Therapies on Rate of Colectomy in Paediatric-onset Ulcerative Colitis - A Population-Based Cohort Study.

AIM: Biologic therapies have been associated with reduced rate of colectomy in ulcerative colitis (UC) in adults, but data are limited in paediatric-onset UC. Our aim was to define the rate of colectomy in paediatric-onset UC, including post-transition into adult care, and to evaluate the impact of biologic therapies on rate of colectomy. METHOD: All prevalent patients diagnosed with paediatric-onset UC in South-East Scotland were identified from a prospectively accrued database at our regional tertiary centre. Patients exposed to biologics or surgery were identified and further data collected from health records. Kaplan-Meier analysis was used to calculate cumulative risk of colectomy over time. RESULTS: 145 prevalent patients were identified between 2000 and 2021. Median follow-up was 7.9 years (IQR 4.1-13.1). 23 patients (16 %) underwent a colectomy. 50/145 (34 %) patients received biologic therapy, and 13/23 (57 %) patients who underwent colectomy received biologics. The cumulative risk of colectomy across the whole cohort at 1, 5, and 10 years was 3 %, 13 % and 16 %, respectively. Patients exposed to biologics had a higher colectomy rate at 5 and 10 years (22 % and 34 %). Patients in the pre-biologic era (2000-2008) had non-significantly reduced time from diagnosis to colectomy (2.4 vs 3.7 years, p = 0.204). CONCLUSION: We have defined the 1-, 5-, and 10-year colectomy rate in a population-based cohort of Paediatric-onset UC patients. Patients who received biologic therapy had a significantly increased risk of colectomy. Increased severity of disease in these patients may account for the greater colectomy risk. LEVEL OF EVIDENCE: Level 1.

A Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of (Thetanix) Bacteroides thetaiotaomicron in Adolescent Crohn's Disease.

INTRODUCTION: Thetanix (gastroresistant capsules containing lyophilized Bacteroides thetaiotaomicron) is a live biotherapeutic, under development for Crohn's disease, that antagonizes transcription factor nuclear factor kappa B, reducing proinflammatory cytokines, particularly tumor necrosis factor alpha. We aimed to assess safety and tolerability in adolescents with Crohn's disease in remission. METHODS: Subjects who were 16-18 years with Crohn's in remission (weighted pediatric Crohn's disease activity index <12.5) were recruited. Each active dose comprised ∼108.2±1.4 colony forming units of B. thetaiotaomicron (randomized 4:1 active:placebo). Part A was single dose. Part B involved 7.5 days twice daily dosing. Serial stools were analyzed for calprotectin, 16S rRNA sequencing, and B. thetaiotaomicron real-time polymerase chain reaction. Bloods were taken serially. Subjects reported adverse events and recorded temperature twice daily. RESULTS: Fifteen subjects were treated-8 in part A (75% men, median 17.1 years) and 10 in part B, including 3 from part A (80% men, median 17.1 years); all 18 completed. Seventy percent took concurrent immunosuppression. Reported compliance was >99% in part B. Two subjects reported adverse events deemed related-one in part A with eructation, flatulence, and reflux; one in part B with dizziness, abdominal pain, and headache. No serious adverse events were reported. There was no significant change in median calprotectin across part B (87.8 [4.4-447] to 50.5 [5.3-572], P = 0.44 by the Fisher exact test in the active group). No significant differences were found in microbiota profiles, but diversity seemed to increase in treated subjects. DISCUSSION: Thetanix, after single and multiple doses, was well tolerated. Although the numbers in this study were small, the safety profile seems good. Future studies should explore efficacy.

Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN.

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

5-Hydroxyvitamin D concentration in paediatric cancer patients from Scotland: a prospective cohort study.

Children with cancer are potentially at a high risk of plasma 25-hydroxyvitamin D (25(OH)D) inadequacy, and despite UK vitamin D supplementation guidelines their implementation remains inconsistent. Thus, we aimed to investigate 25(OH)D concentration and factors contributing to 25(OH)D inadequacy in paediatric cancer patients. A prospective cohort study of Scottish children aged 75 nmol/l). In all, eighty-two patients (median age 3·9, interquartile ranges (IQR) 1·9-8·8; 56 % males) and thirty-five controls (median age 6·2, IQR 4·8-9·1; 49 % males) were recruited. 25(OH)D inadequacy was highly prevalent in the controls (63 %; 22/35) and in the patients (64 %; 42/65) at both baseline and during treatment (33-50 %). Non-supplemented children had the highest prevalence of 25(OH)D inadequacy at every stage with 25(OH)D median ranging from 32·0 (IQR 21·0-46·5) to 45·0 (28·0-64·5) nmol/l. Older age at baseline (R -0·46; P<0·001), overnutrition (BMI≥85th centile) at 3 months (P=0·005; relative risk=3·1) and not being supplemented at 6 months (P=0·04; relative risk=4·3) may have contributed to lower plasma 25(OH)D. Paediatric cancer patients are not at a higher risk of 25(OH)D inadequacy than healthy children at diagnosis; however, prevalence of 25(OH)D inadequacy is still high and non-supplemented children have a higher risk. Appropriate monitoring and therapeutic supplementation should be implemented.

Wedding Imagery and Public Support for Gay Marriage.

This study uses an experiment embedded in a large, nationally representative survey to test whether exposure to imagery of a gay or lesbian couple's wedding influences support for gay marriage. It also tests whether any such effects depend on the nature of the image (gay or lesbian couple, kissing or not) and viewer characteristics (sex, age, race, education, religion, and ideology). Results show that exposure to imagery of a gay couple kissing reduced support for gay marriage relative to the baseline. Other image treatments (gay couple not kissing, lesbian couple kissing, lesbian couple not kissing) did not significantly influence opinion.

Effects of pediatric cancer and its treatment on nutritional status: a systematic review.

CONTEXT: Malnutrition in pediatric cancer is common worldwide, yet its prevalence and effects on clinical outcomes remain unclear. OBJECTIVE: The aim of this review was to evaluate primary research reporting the prevalence of malnutrition in pediatric cancer patients and to assess the effects of pediatric cancer and its treatment on nutritional status. DATA SOURCES: Electronic databases of MEDLINE, CINHAL, and PubMed were searched (January 1990-February 2013). STUDY SELECTION: Studies of patients aged <18 years who were diagnosed with and treated for cancer and for whom measurements of anthropometry were reported and included. The primary outcome was the prevalence of malnutrition (undernutrition and overnutrition), expressed as body mass index (BMI), in children diagnosed with and treated for cancer. DATA EXTRACTION: Evidence was appraised critically by employing the Critical Appraisal Skills Program tool, and data was extracted from original articles. DATA SYNTHESIS: A total of 46 studies were included, most of which were considered to be of low quality on the basis of heterogeneity in both the criteria and the measurements used to define malnutrition. Undernutrition was identified by measuring BMI, weight loss, mid-upper arm circumference, and triceps skinfold thickness, while overnutrition was assessed using BMI. Overall, the prevalence of undernutrition ranged from 0% to 65% and overnutrition from 8% to 78%. Finally, undernutrition in pediatric cancer at diagnosis was associated with poor clinical outcomes in 6 of 9 studies. CONCLUSION: The possibility of a high prevalence of malnutrition in childhood cancer, indicated by the studies reviewed, highlights the need for high-quality, population-based, longitudinal studies using standard criteria to identify malnutrition.

Probiotics for necrotizing enterocolitis: a systematic review.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most commonly acquired neonatal intraabdominal emergency and causes significant morbidity and mortality. A proposed strategy for the prevention of NEC is the administration of oral probiotics. Probiotics have been shown to reduce NEC in experimental rat models and have been used in clinical trials. The authors aimed to review the existing data on the use of oral probiotics for the prevention of NEC in preterm infants (age <33 weeks) and those with very low birth weight (VLBW). MATERIALS AND METHODS: Systematic review of randomized controlled trials (RCTs) and quasi-RCTs was performed to find outcome measures of incidence, severity, need for surgery, and mortality in NEC. Electronic searches were performed on Medline and CINAHL databases using key word and subject headings with combinations of the terms "infant, preterm"; "infant, VLBW"; "enterocolitis, necrotizing"; and "probiotics." In addition, citation searches were performed for all potential studies. RESULTS: Six potential RCTs were identified for inclusion, but there were no systematic or Cochrane database reviews identified. One study was discounted because of the use of historical controls, so 5 studies were selected for analysis. Cumulatively, 640 infants were treated with probiotics and 627 were used as control subjects. All of the studies showed a trend toward less NEC in the treatment group. The heterogeneity of probiotic formulations and the timing and methods of interventions in the identified studies made synthesis and comparison of data inappropriate. CONCLUSIONS: The data appear to lend support to the use of oral probiotics for the prevention of NEC in preterm infants and those with VLBW. However, the data are insufficient to comment on their short- and long-term safety. Type of probiotics used, as well as the timing and dosage, are still to be optimized. Further understanding of the pathogenesis of NEC and the mechanisms by which probiotics prevent it may lead to evidence-based treatment strategies.

Development drivers for waste management.

This paper identifies six broad groups of drivers for development in waste management. Public health led to the emergence of formalized waste collection systems in the nineteenth century, and remains a key driver in developing countries. Environmental protection came to the forefront in the 1970s, with an initial focus on eliminating uncontrolled disposal, followed by the systematic increasing of technical standards. Today, developing countries seem still to be struggling with these first steps; while climate change is also emerging as a key driver. The resource value of waste, which allows people to make a living from discarded materials, was an important driver historically, and remains so in developing countries today. A current trend in developed countries is closing the loop, moving from the concept of 'end-of-pipe' waste management towards a more holistic resource management. Two underpinning groups of drivers are institutional and responsibility issues, and public awareness. There is no, one single driver for development in waste management: the balance between these six groups of drivers has varied over time, and will vary between countries depending on local circumstances, and between stakeholders depending on their perspective. The next appropriate steps towards developing a sustainable, integrated waste management system will also vary in each local situation.