Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115.

Measuring body composition in pediatric patients with complex diagnoses: Acceptability, practicality, and validation of different techniques.

BACKGROUND: Body composition could help identify malnutrition in pediatric patients, but there is uncertainty over which techniques are most suitable and prevailing opinion that measurements are difficult to obtain in practice. This study examined the acceptability, practicality, reliability, and validity of different anthropometric and body composition measurements in patients with complex diagnoses in a tertiary pediatric hospital. METHODS: A total of 152 children aged 5-18 years had weight, height, body mass index (BMI), mid-upper arm circumference (MUAC), 4-site skinfold thicknesses (SFT), bioelectrical impedance analysis (BIA), and dual-energy x-ray absorptiometry (DXA) assessed on admission and discharge. Acceptability was assessed in a continuous scale, practicality with number/percentage of successful measurements, reliability with intraclass correlation coefficients and coefficients of repeatability, and validity between "simpler" techniques and DXA with Bland-Altman analysis of agreement and Cohen kappa. RESULTS: Techniques were overall acceptable. Measurements were successful in >50%, with patient refusal uncommon. Coefficients of repeatability were good (0.3 cm MUAC and height, 0.2 kg weight, and 1.0 mm SFTs). All techniques significantly overestimated DXA fat mass, but BMI and triceps SFT better identified abnormal fat mass (κ = 0.46 and 0.49). BIA fat-free mass was not significantly different from DXA, with substantial agreement between techniques (κ = 0.65). CONCLUSION: Body composition by a range of techniques is acceptable, practical, and reliable in a diverse group of children with complex diagnoses. BIA seems a good alternative to DXA for assessing fat-free mass, triceps SFT, and BMI for fat mass but should be used with care as it could overestimate total fat mass in individuals.

Risk factors for catheter-related bloodstream infections associated with home parental nutrition in children with intestinal failure: A prospective cohort study.

BACKGROUND & AIMS: Catheter-related bloodstream infection (CRBSI) is the most common, potentially life-threatening complication of long-term parenteral nutrition (PN). We prospectively assessed the incidence and risk factors for CRBSI in children receiving long-term home PN (HPN) for intestinal failure (IF) in a single IF rehabilitation center. METHODS: Data regarding episodes and potential risk factors for CRBSI in children on HPN were prospectively recorded. RESULTS: Forty-one of 75 children were diagnosed with CRBSI. The overall CRBSI rate was 1.61 per 1000 catheter days. The indications for HPN were gastrointestinal motility disorders in 35%, short bowel syndrome (SBS) in 28% graft versus host disease (GvHD) post bone marrow transplant in 17%, congenital enteropathy in 15%, and severe neurodevelopmental impairment in 5%. Gastrointestinal motility disorders had significantly higher CRBSI rate compared to other groups (p < 0.0005; 2.74 in motility group vs 1.54 in GvHD group vs 0.52 in congenital enteropathies vs 0.36 in SBS group vs 0.67 in severe neurodevelopmental delay). Multivariate analysis revealed that enterocutaneous distal stoma (ileostomy or colostomy) (HR 3.35 [95% CI, 1.63-6.86]; p < 0.001), age <2 years (HR 0.28 [95% CI, 0.15-0.53]; p < 0.0001), male sex (HR 2.28 [95% CI, 1.51-3.43]; p < 0.0001), non-use of taurolidine citrate lock (HR 2.70 [95% CI, 1.72-4.11]; p < 0.0001) and gastrointestinal motility disorder (HR 3.02 [95% CI, 1.81-4.91]; p < 0.001) were independent risk factors for developing CRBSI. CONCLUSIONS: Extra care in managing PN connections and disconnections should be taken in children with an underlying gastrointestinal motility disorder, distal enterocutaneous stoma, male sex and those aged <2 years since they are at a significantly higher risk of CRBSI. Early introduction of taurolidine lock should be considered.

Causes and Outcome of Central Venous Catheter Repair in Children with Intestinal Failure on Home Parenteral Nutrition.

OBJECTIVES: Children requiring a central venous catheter (CVC) for long-term parenteral nutrition (PN) are at risk of CVC breakage. Modern intestinal failure (IF) management aims to preserve vascular access sites. CVC repair rather than removal is hence attempted for broken catheters. The aim of this study was to describe causes and outcomes of CVC repairs in home PN dependent children. METHODS: All patients (ages 0-17 years) with CVC dependency enrolled in the IF rehabilitation program of a pediatric referral center were identified, and those who underwent a CVC repair between January 2019 and November 2020 included. Data on associated cause for breakage and incidence of central line-associated bloodstream infections (CLABSIs) post repair were documented retrospectively. Descriptive statistics including medians, percentages, and frequencies were used. RESULTS: Forty children, 15 males (37%) and 25 females (63%), were identified. Fifteen of 40 (37.5%) patients underwent a total of 29 CVC repairs (0.1 repairs per 1000 catheter days); 8 of 15 (53%; 33% females) were <5 years of age. The most common reason for repair was CVC fracture by biting (41%) followed by catheter occlusion with intraluminal PN deposition (13.2%). Repair was successful in 100% cases. Only 1 patient had a confirmed CLABSI post repair (1/29 repairs; 3%) who presented 3 days late after the initial catheter breakage. Catheter salvage was successful with antibiotics. CONCLUSION: CVC repair in our cohort was very successful and infection rate after repair minimal. CVC repair rather than removal is recommended to preserve central venous access.

Assessment of the FreeStyle Libre 2 interstitial glucose monitor in hypo- and euglycemic cats.

BACKGROUND: Continuous glucose monitoring systems have been validated for eu- and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). OBJECTIVES: Assess FSL2 accuracy in cats with hypoglycemia. ANIMALS: Nine healthy, purpose-bred cats. METHODS: Hyperinsulinemic-hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland-Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P < .05 considered significant). RESULTS: Overall, BG and IG correlated strongly (r = 0.83, P < .0001) in stable glycemia and moderately at all rates of change (r = 0.69, P < .0001). Interstitial glucose concentration underestimated BG in euglycemia, but the BG-IG difference was progressively smaller as BG decreased (12.9 ± 12.2, 8.8 ± 11.2, -3.2 ± 7.4, and -7.8 ± 5.2 mg/dL in the ranges of 80-120 [n = 64], 60-79 [n = 29], 50-59 [n = 71], and 29-49 mg/dL [n = 53], respectively). CONCLUSIONS: Although IG underestimates BG throughout most of the hypo-euglycemic range, IG generally overestimates BG in marked hypoglycemia (<60 mg/dL). It is therefore imperative to evaluate FSL2 results in this critical range with caution.

Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support.

OBJECTIVES: Our objective was to evaluate the short- and long-term safety and efficacy of teduglutide treatment in infants and children with short bowel syndrome with intestinal failure (SBS-IF). METHODS: Two open-label phase 3 studies and 1 extension study investigated the short- and long-term safety and efficacy of teduglutide (0.05 mg/kg/day) in infants and children with SBS-IF: NCT03571516, 24-week study of infants who were randomized to receive teduglutide or standard of care (SoC); NCT02980666, 24-week study of infants and children who all received teduglutide; and NCT03268811, 24-week extension study of patients who completed NCT02980666 (patients could receive up to 48 weeks of total treatment). RESULTS: Twelve infants and 8 children enrolled in the core studies, and 2 infants and 7 children in the extension study. After 24 weeks of treatment, parenteral support (PS) requirements reduced by ≥20% from baseline for 4 infants (57.1%) and 4 children (66.7%) receiving teduglutide and for 2 infants receiving SoC (50.0%). One infant (50.0%) and 4 children (80.0%) receiving teduglutide maintained the ≥20% reduction in PS at 48 weeks of treatment. Two children receiving teduglutide achieved enteral autonomy, after 12 weeks and 28 weeks of treatment, respectively. All adverse events (AEs) were in line with known impacts of SBS-IF and adverse reactions to teduglutide. Only one serious AE (abdominal pain) was considered related to teduglutide. CONCLUSIONS: Short- and long-term treatment with teduglutide resulted in clinically meaningful reductions in PS requirements for infants and children with SBS-IF. Teduglutide was well tolerated, and efficacy improved with longer-term treatment.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 2: Long-Term Follow-Up on Home Parenteral Nutrition.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications, and on possible surgical and medical management to increase intestinal absorption.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 1: From Intestinal Resection to Home Discharge.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. The first part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN.

Optimizing nutrition IN pediatric intestinal pseudo-obstruction syndrome.

BACKGROUND: Pediatric intestinal pseudo-obstruction (PIPO) encompasses a variety of rare, heterogeneous, and disabling disorders that severely affect gastrointestinal motility and are associated with high morbidity and mortality. PIPO management is complex and focuses on maintaining an optimal nutritional status, improving gut function, relieving symptoms, and treating complications. Nutritional issues prevail, and PIPO patients often experience severe undernutrition and faltering growth. Thus, nutritional management plays a pivotal role for achieving the most favorable clinical outcomes. The calorie and nutrient intake of each patient needs to be tailored to age, extent and severity of gut involvement and nutritional needs to support an optimal nutritional status. After defining the extent and severity of gut dysmotility, an experienced team should perform a careful nutritional assessment. An oral diet should always be encouraged and might include bite and dissolve solids, liquid diet or simple oral stimulation. If oral caloric intake is inadequate, liquid gastric feeds should provide the subsequent step. In the presence of severe gastric dysmotility, continuous post-pyloric feeding represents a viable option. In the most severe cases, parenteral nutrition (PN) is required to meet appropriate nutritional requirements. PURPOSE: Pediatric data on this topic are scarce and mainly extrapolated from adult studies. In this review, we discuss current evidence and knowledge regarding nutritional options, implications of the use of different feed types, including a blended diet, and the use of PN. Moreover, based on our experience and the evidence from the literature, we propose a flow chart to guide the nutritional management of PIPO patients.

Integration of Patient-Reported Outcome Measures in the Electronic Health Record: The Veterans Affairs Experience.

PURPOSE: There are growing efforts to integrate patient-reported outcome (PRO) data into electronic health records (EHRs) to bring together disparate sources of patient information and improve medical care. PRO measures can be used to assess cancer symptom presence and severity. Integrating PRO tools in EHRs can alert providers to address symptoms, which is an essential component of comprehensive oncology care. METHODS: We modified a PRO used to measure cancer and end-of-life symptoms, the Edmonton Symptom Assessment System to create the Veteran Symptom Assessment System (VSAS). VSAS was implemented as an integrated PRO as part of the Veterans Administration EHR system and was used at hematology-oncology clinics in Veteran Administration (VA) medical centers in the Southeast. RESULTS: From 2013 to 2014, VSAS was introduced, underwent usability testing and modifications, and was finally implemented in the EHR. Between 2015 and 2019, VSAS was administered 43,883 times in 9,058 patients. Eighty-nine percent of Veterans were male, 11% were female, 52% identified as non-Hispanic White, and 43% identified as African American. Fatigue, shortness of breath with exertion, and pain were most frequently reported initially (68%, 48%, and 45%, respectively) and were most frequently rated as severe (27%, 16%, and 17%, respectively). In patients diagnosed with stage IV cancer, higher symptom burden was significantly associated with shorter overall survival. The majority of Veterans with longitudinal measurements experienced improvement in symptoms, most frequently in severe symptoms. CONCLUSION: To our knowledge, this is the first large-scale implementation of a PRO system, integrated in the VA EHR, in ambulatory patients with cancer and blood disorders. The integration of VSAS within the VA EHR is a significant demonstration and a necessary requirement for current and future systemic initiatives in cancer symptom management.

Anaemia in Children Receiving Home Parenteral Nutrition: A Common Problem?

OBJECTIVES: Children receiving home parenteral nutrition (HPN) are at risk of iron deficiency anaemia. Our aim was to determine the incidence of iron deficiency anaemia in paediatric HPN and efficacy of each therapeutic approach. METHODS: Retrospective data collection from children receiving HPN at a tertiary referral centre over a 12-month period (2015). Full blood count, and whenever available, ferritin and C-reactive protein were collected at least 3 times for each patient. Liver function tests were checked at the beginning and end of the study and number of blood transfusions/iron infusions recorded. RESULTS: Forty-one HPN patients (61% girls; 51% motility disorder, 29% enteropathy, 20% short bowel syndrome) were identified. Eighty-three percent of children were anaemic at the beginning of the study with the number decreasing to 73% by the end. Iron deficiency anaemia was most commonly seen and treated with blood transfusion in 46% of cases and iron infusions in 29%. There was no statistical difference in the level of haemoglobin improvement between the 2 treatments (50% vs 33%, P  = 0.657) nor a significant difference in haemoglobin (g/L) level achieved. The results for both were, however, more favourable in the infusion group. Patients receiving transfusions had a significantly higher incidence of abnormal liver function compared with those who hadinfusions (93% vs 37%, P = 0.009). CONCLUSIONS: Iron deficiency anaemia is common in children receiving HPN. A large proportion of patients still receive blood transfusions as first-line therapy but intravenous iron can be a suitable alternative. Treatment guidelines are required.

Patient-level costing analysis of paediatric short bowel syndrome care in a specialist tertiary centre.

PURPOSE: To undertake a pilot study estimating patient-level costs of care for paediatric short bowel syndrome (SBS) from the healthcare provider perspective. METHODS: A pilot group of patients with anatomical SBS was selected at a single specialist tertiary centre in the United Kingdom. The Patient Level Information and Costing System (PLICS) was used to extract costing data for all hospital-based activities related to SBS, from the implementation of PLICS in 2016 to April 2021. Patient-specific and pooled data were reported descriptively in per patient-year terms. RESULTS: Five patients had full PLICS data available for the 5-year study period and 2 patients had 4 years of data. The median cost for hospital care of SBS was £52,834 per patient-year (range £1804-£331,489). The key cost drivers were inpatient beds, pharmacy, and staffing costs, which made up > 60% of annual costs. In the first 3 years following index admission (n = 2), there was a steady decline in the annual cost of care to a level comparable with patients with established SBS. CONCLUSION: Patient-level cost of care analysis for SBS is feasible using PLICS. Hospital-related costs vary widely between and within individual patients over time. Key drivers of cost are related to complications of SBS.

Designing and Implementing a Family Literacy Program Through Smartphones: How Does Recruitment Method Influence Uptake and Attrition?

Texting-based programs are increasingly used to support parents as their child's first teacher and create links between home and school. However, there is scant evidence about the influence of program implementation on parent uptake and attrition-a key component of such programs. This article describes the design and delivery of Kindytxt, a literacy-based text-messaging program for parents with a child at Kindergarten in Western Australia, and examines the influence of recruitment method, area socioeconomic status, and teacher participation on parent uptake and attrition. Results indicate that embedding Kindytxt into a well-established family literacy program provided the infrastructure and mechanism for extensive program reach, and the recruitment method, specifically the involvement of the kindergarten teacher, significantly influenced parent registration. However, attrition rates were not significantly affected by the area socioeconomic status of participating schools, recruitment method, nor teacher participation in Kindytxt. The results suggest that teacher involvement may be the crucial factor in enabling parents to access texting programs, regardless of the socioeconomic status of the school community. The design elements may be used to inform future program development, and the research results highlight the importance of documenting and including the method of delivery as variables in the evaluation of program implementation.

Use of home parenteral nutrition in severely neurologically impaired children.

OBJECTIVE: To review the outcome of children with severe neurological impairment (NI) and intestinal failure (IF) referred to our specialist multidisciplinary IF rehabilitation service and to discuss implications. DESIGN: Case report series, descriptive analysis. SETTING: IF rehabilitation programme at a tertiary children's hospital in the UK. PATIENTS: Children with severe NI referred to our IF rehabilitation programme from 2009 to 2019. MAIN OUTCOME MEASURES: Demographic and social data, diagnosis, clinical condition, use of home parenteral nutrition (HPN), complications, ethics review outcome and advance care plans. RESULTS: Six patients with severe NI were referred to our IF rehabilitation service. Consent for publication was obtained from five families. After thorough medical review and clinical ethics committee assessment, three children started HPN, one had intravenous fluids in addition to enteral feed as tolerated and one intravenous fluids only. The HPN children survived 3-7.08 years (median 4.42 years) on treatment. Objective gastrointestinal signs, for example, bleeding improved without excessive HPN-related complications. Symptomatic improvement was less clear. Analgesia was reduced in three of the five children. All cases had detailed symptom management and advance care plans regularly updated. CONCLUSIONS: HPN can play a role in relieving gastrointestinal signs/symptoms in children with severe NI and IF. HPN can be conceptualised as part of good palliative care if judged to be in the child's best interests. However, given its risks and that HPN has the potential to become inappropriately life-sustaining, a thorough ethics review and evaluation should be performed before it is initiated, withheld or withdrawn in children with severe NI.

Results of an International Survey on Feeding Management in Infants With Short Bowel Syndrome-Associated Intestinal Failure.

OBJECTIVES: Short bowel syndrome (SBS) is a complex and rare condition (incidence 1200/100,000 live births) that requires a multidisciplinary team approach to management. In January 2019, the first European Reference Network on Rare and Inherited Congenital Anomalies (ERNICA) Intestinal Failure (IF) workshop was held. Several questions about the strategies used in managing IF associated with SBS were devised. The aim of our study was to collect data on the enteral feeding strategies adopted by the ERNICA centres. METHODS: A questionnaire (36 questions) about strategies used to introduce enteral nutrition post-operatively and start complementary food/solids in infants with SBS associated IF was developed and sent to 24 centres in 15 countries that participated in the ERNICA-IF workshop. The answers were collated and compared with the literature. RESULTS: There was a 100% response rate. In infants, enteral nutrition was introduced as soon as possible, ideally within 24-48 hours post-small intestinal surgical resection. In 10 of 24 centres, bolus feeding was used, in nine continuous, and in five a combination of both. Twenty-three centres used mothers' own milk as the first choice of feed with extensively hydrolysed feed, amino acid-based feed, donor human milk or standard preterm/term formula as the second choice. Although 22 centres introduced complementary/solid food by 6 months of age, food choice varied greatly between centres and appeared to be culturally based. CONCLUSIONS: There is diversity in post-surgical enteral feeding strategies among centres in Europe. Further multi-centre studies could help to increase evidence-based medicine and management on this topic.

Evaluating the performance of a clinical genome sequencing program for diagnosis of rare genetic disease, seen through the lens of craniosynostosis.

PURPOSE: Genome sequencing (GS) for diagnosis of rare genetic disease is being introduced into the clinic, but the complexity of the data poses challenges for developing pipelines with high diagnostic sensitivity. We evaluated the performance of the Genomics England 100,000 Genomes Project (100kGP) panel-based pipelines, using craniosynostosis as a test disease. METHODS: GS data from 114 probands with craniosynostosis and their relatives (314 samples), negative on routine genetic testing, were scrutinized by a specialized research team, and diagnoses compared with those made by 100kGP. RESULTS: Sixteen likely pathogenic/pathogenic variants were identified by 100kGP. Eighteen additional likely pathogenic/pathogenic variants were identified by the research team, indicating that for craniosynostosis, 100kGP panels had a diagnostic sensitivity of only 47%. Measures that could have augmented diagnoses were improved calling of existing panel genes (+18% sensitivity), review of updated panels (+12%), comprehensive analysis of de novo small variants (+29%), and copy-number/structural variants (+9%). Recent NHS England recommendations that partially incorporate these measures should achieve 85% overall sensitivity (+38%). CONCLUSION: GS identified likely pathogenic/pathogenic variants in 29.8% of previously undiagnosed patients with craniosynostosis. This demonstrates the value of research analysis and the importance of continually improving algorithms to maximize the potential of clinical GS.

Surgery and opioids: evidence-based expert consensus guidelines on the perioperative use of opioids in the United Kingdom.

There are significant concerns regarding prescription and misuse of prescription opioids in the perioperative period. The Faculty of Pain Medicine at the Royal College of Anaesthetists have produced this evidence-based expert consensus guideline on surgery and opioids along with the Royal College of Surgery, Royal College of Psychiatry, Royal College of Nursing, and the British Pain Society. This expert consensus practice advisory reproduces the Faculty of Pain Medicine guidance. Perioperative stewardship of opioids starts with judicious opioid prescribing in primary and secondary care. Before surgery, it is important to assess risk factors for continued opioid use after surgery and identify those with chronic pain before surgery, some of whom may be taking opioids. A multidisciplinary perioperative care plan that includes a prehabilitation strategy and intraoperative and postoperative care needs to be formulated. This may need the input of a pain specialist. Emphasis is placed on optimum management of pain pre-, intra-, and postoperatively. The use of immediate-release opioids is preferred in the immediate postoperative period. Attention to ensuring a smooth care transition and communication from secondary to primary care for those taking opioids is highlighted. For opioid-naive patients (patients not taking opioids before surgery), no more than 7 days of opioid prescription is recommended. Persistent use of opioid needs a medical evaluation and exclusion of chronic post-surgical pain. The lack of grading of the evidence of each individual recommendation remains a major weakness of this guidance; however, evidence supporting each recommendation has been rigorously reviewed by experts in perioperative pain management.

Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure: Pooled Analysis of 4 Clinical Studies.

BACKGROUND: This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF). METHODS: Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included. RESULTS: Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred. CONCLUSION: Based on integrated data from 4 clinical studies, including long-term follow-up for ≤161 weeks, teduglutide had a safety profile consistent with the individual core pediatric studies and as expected for pediatric patients with SBS-IF who never received teduglutide. The most frequent AEs reflected treatment with teduglutide, complications of the underlying disease, and typical childhood illnesses.