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Introduction: The management of pediatric inflammatory bowel disease (PIBD) has drastically changed in the last decade. The limited availability of new biologics or small molecule therapies, and concerns about durability in children has necessitated the development of other advances in management to optimize care. Areas covered: This review covers guidance for management targets and advances in optimizing biologic therapies, new medical therapies, adjuvant therapies, precision medicine and mental health concerns in PIBD. This review focused on recent advances and was not intended as a complete overview of the investigations and management of pediatric IBD. Expert opinion: Advancements include standardization of treatment goals via a treat-to-target strategy, optimizing anti-TNF biologics through combination therapy or proactive drug monitoring, earlier initiation of treatment for Crohn's disease, the emergence of new biologic/advanced therapies and a growing focus on adjuvant therapies targeting the microbiome. Future progress relies on the inclusion of children/adolescents in clinical trials to facilitate faster regulatory approval for pediatric therapies and the integration of precision medicine and mental health screening to improve patient care and outcomes. [ABSTRACT FROM AUTHOR]

Clinicians, researchers, regulators, and other decision-makers increasingly rely on evidence from real-world data (RWD), including data routinely accumulating in health and administrative databases. RWD studies often rely on algorithms to operationalize variable definitions. An algorithm is a combination of codes or concepts used to identify persons with a specific health condition or characteristic. Establishing the validity of algorithms is a prerequisite for generating valid study findings that can ultimately inform evidence-based health care. In this paper, we aim to systematize terminology, methods, and practical considerations relevant to the conduct of validation studies of RWD-based algorithms. We discuss measures of algorithm accuracy, gold/reference standards, study size, prioritization of accuracy measures, algorithm portability, and implications for interpretation. Information bias is common in epidemiologic studies, underscoring the importance of transparency in decisions regarding choice and prioritizing measures of algorithm validity. The validity of an algorithm should be judged in the context of a data source, and one size does not fit all. Prioritizing validity measures within a given data source depends on the role of a given variable in the analysis (eligibility criterion, exposure, outcome, or covariate). Validation work should be part of routine maintenance of RWD sources. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Background and aims: There is an incomplete understanding of the full safety profiles of repeated COVID-19 vaccinations in patients with inflammatory bowel disease (IBD). Among individuals with IBD, we assessed whether COVID-19 vaccines were associated with serious adverse events of special interest (AESI) and health care utilization [all-cause hospitalizations, Emergency Department (ED) visits, gastroenterology visits, IBD-related visits]. Methods: Using comprehensive administrative health data from Ontario, Canada, adults with IBD who received at least one COVID-19 vaccine from December 2020-January 2022 were included. Self-controlled case series analyses were conducted to evaluate the relative incidence rates of AESI and health care utilization outcomes across post-vaccination risk and control periods. Results: Among 88,407 IBD patients, 99.7% received mRNA vaccines and 75.9% received ≥ 3 doses. Relative to control periods, we did not detect an increase in AESI. IBD patients had fewer all-cause hospitalizations during post-vaccination risk periods. Patients experienced more all-cause ED visits after dose 2 [Relative Incidence (RI):1.08(95%CI:1.04–1.12)] but fewer visits after doses 3 [RI:0.85 (95%CI:0.81–0.90)] and 4 [RI:0.73 (95%CI:0.57–0.92)]. There was no increase in gastroenterologist visits or IBD-related health care utilization post-vaccination. There were fewer IBD-related hospitalizations after dose 1 [RI:0.84 (95%CI:0.72–0.98)] and 3 [RI:0.63 (95%CI:0.52–0.76)], fewer IBD-related ED visits after dose 3 [RI:0.81 (95%CI:0.71–0.91)] and 4 [RI:0.55 (95%CI:0.32–0.96)], and fewer outpatient visits after dose 2 [RI:0.91 (95%CI:0.90–0.93)] and 3 [RI:0.87 (95%CI:0.86–0.89)]. Conclusion: This population-based study did not detect increased AESI, all-cause or IBD-related health care utilization following COVID-19 vaccination, suggesting a lack of association between vaccination and increased disease activity. [ABSTRACT FROM AUTHOR]

Background: When constipation is refractory to first‐line interventions, antegrade enema use may be considered. We aimed to assess the impact of this intervention on healthcare utilization. Methods: We conducted a population‐based, quasi‐experimental study with pre–post comparison of the intervention group and a non‐equivalent control group using linked clinical and health administrative data from Ontario, Canada. Subjects included children (0–18 years) who underwent antegrade enema initiation from 2007 to 2020 and matched controls (4:1) from the general population. To assess the change in healthcare utilization following antegrade enema initiation, we used negative binomial generalized estimating equations with covariates selected a priori. Key Results: One hundred thirty‐eight subjects met eligibility criteria (appendicostomy = 55 (39.9%); cecostomy tube = 83 (60.1%)) and were matched to 550 controls. There was no significant difference in the change in the rate of hospitalizations (rate ratio (RR) 1.05, 95% confidence interval (CI) 0.35–1.75), outpatient visits (RR 1.05, 95% CI 0.91–1.18), or same‐day surgical procedures (RR 1.51, 95% CI 0.60–2.43) across cases in 2 years following antegrade enema initiation compared with controls. Cases had an increased rate of emergency department (ED) visits, which was not observed in controls (RR 1.52, 95% CI 1.11–1.79), driven in part by device‐related complications. Conclusions and Inferences: Understanding healthcare utilization patterns following antegrade enema initiation allows for effective health system planning and aids medical decision‐making. The observed increase in ED visits for device‐related complications speaks to the need to improve preventive management to help mitigate emergency care after initiation of antegrade enemas. [ABSTRACT FROM AUTHOR]

Problem: Ambiguity in communication of key study parameters limits the utility of real‐world evidence (RWE) studies in healthcare decision‐making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias. What We Did: The International Society for Pharmacoepidemiology (ISPE) and ISPOR–The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision‐making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The overarching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision‐making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility. Strategies to Disseminate and Facilitate Use: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years. Conclusion: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions. [ABSTRACT FROM AUTHOR]

Background: Surgery for inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolism (VTE) during hospitalization. It is unclear whether this association persists after hospital discharge. Aims: We assessed the association between surgery and VTE following hospital discharge in IBD. Methods: We conducted a population-based cohort study between 2002 and 2016 in Ontario, Canada. Adults with IBD hospitalized for ≥ 72 h who underwent an intra-abdominal surgery were compared to hospitalized, nonsurgical IBD patients. Multivariable Cox proportional hazard models were used to compare VTE risk within 12 months of discharge. Results: A total of 80,445 hospital discharges were analyzed: 60% Crohn's disease (CD) and 40% ulcerative colitis (UC). The median time to VTE was three times longer for nonsurgical patients with CD and 1.6 times longer for nonsurgical patients with UC. Compared with nonsurgical patients, surgery for CD was associated with a lower cumulative risk of VTE in the 2 weeks after discharge and persisted through to 12 months after discharge (adjusted HR 0.24; 95% CI 0.15–0.40). In contrast, urgent surgery for UC was associated with an increased risk of VTE. The increased risk was greatest at 2 weeks after discharge (aHR, 1.80; 95% CI 1.26–2.57) and declined progressively over the course of 12 months. Conclusions: Surgery was associated with a greater risk of VTE after hospital discharge in UC but not CD. In patients with UC who have undergone urgent surgery, healthcare providers should consider an extended period of prophylaxis after hospital discharge. [ABSTRACT FROM AUTHOR]

Background: Transition in care is defined as the "purposeful and planned movement of adolescents and young adults with a chronic medical condition from pediatric to adult-oriented healthcare systems/care providers." Currently, there are no Level 1 evidence-based interventions to improve the care of transitioning adolescents and young adults (AYAs) with inflammatory bowel disease (IBD). The development of a transition program using a biopsychosocial approach will improve the standards for healthcare delivery to transitioning IBD patients. This is a protocol for a structured randomized controlled trial (RCT) to assess the clinical and implementation effectiveness of a multimodal intervention focused on improving patient function, transition readiness and outcomes among AYA patients with IBD being cared for at pediatric centers in Canada.Methods: This multi-center RCT is a type 1 hybrid effectiveness-implementation trial to evaluate effectiveness of the intervention and how it can be implemented more widely after the trial. We will include patients aged 16.0-17.5 years. The intervention program consists of 4 core components: (1) individualized assessment, (2) transition navigator, (3) virtual patient skills-building with a focus on building resilience, self-management and self-efficacy, and (4) a virtual structured education program. The control group will undergo standard-of-care defined by each participating center. The primary outcome will be the IBD Disability Index, a validated measure to assess patient functioning. Secondary outcomes include transition readiness and success, anxiety and depression scales, and health service utilization rates. Additionally, we will measure implementation outcomes and related barriers and facilitators for the intervention program.Discussion: The type 1 hybrid effectiveness-implementation design will allow for the development of a feasible, sustainable, and acceptable final intervention model. The intervention will consist of modules that can be accessed in an online, virtual platform. The implementation will allow centralization of interventions and funding in order to minimize the impact on local clinical practice or hospital resources. The authors anticipate that the main study limitation will relate to study subjects not completely adhering to every component of the intervention, which will be evaluated and addressed using the implementation science approach.Trial Registration: NCT05221281. Registry: ClinicalTrials.gov. Date of registration: February 2, 2022. https://clinicaltrials.gov/ct2/show/NCT05221281 . [ABSTRACT FROM AUTHOR]

Objectives Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. Methods We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n  = 3753) were matched to 5 non-KD controls from the general population (n  = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. Results There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. Conclusion Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD. [ABSTRACT FROM AUTHOR]

Background: Life expectancy in people with inflammatory bowel disease (IBD) has increased but remains shorter than in people without IBD. We describe the life expectancy associated with IBD therapies among the growing number of older adults living with IBD.Methods: Older adults (≥ 65 years) with IBD were identified from population-based health administrative data using a validated algorithm. Life expectancy on patients' 65th birthday, stratified by sex, was calculated using a period life table approach from age- and sex-specific mortality rates among patients receiving immunomodulator monotherapy, biologic monotherapy, combination therapy, mesalamine, systemic steroids, and no therapy.Results: Among 28,260 older adults with IBD (239,125 person-years of follow-up), life expectancy at 65 years was longest for patients taking mesalamine (females: 22.1 years, 95% CI 21.8-22.5; males: 19.6 years, 95% CI 19.3-20.0) and shortest for patients taking steroids (females: 11.7 years, 95% CI 11.0-12.4; males 10.3 years, 95% CI 9.7-10.8). Life expectancy was similar for patients receiving immunomodulator monotherapy and biologic monotherapy. Immunomodulator monotherapy was associated with a reduction in life expectancy compared to combination therapy by 5.1 (95% CI 2.3-7.8) in females and 2.8 years (95% CI 0.1-5.5) in males.Conclusions: Life expectancy varies across therapies used for IBD, with differences likely arising from a combination of medication effectiveness, safety profiles, disease severity, and comorbid conditions. These considerations should be balanced when deciding on a therapeutic approach for the management of IBD in older adults. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is now a global disease with incidence increasing throughout Asia. Aim: To determine the incidence of IBD among South Asians and Chinese people residing in Ontario, Canada's most populous province. Methods: All incident cases of IBD in children (1994– 2015) and adults (1999– 2015) were identified from population-based health administrative data. We classified South Asian and Chinese ethnicity using immigration records and surnames. We determined standardized incidence of IBD and adjusted incidence rate ratio (aIRR) in South Asians and Chinese compared to the general population. Results: Among 16,230,638 people living in Ontario, standardized incidence of IBD per 100,000 person-years was 24.7 (95% CI 24.4– 25.0), compared with 14.6 (95% CI 13.7– 15.5) in 982,472 South Asians and with 5.4 (95% CI 4.8– 5.9) in 764,397 Chinese. The risk of IBD in South Asians was comparable to the general population after adjusting for immigrant status and confounders (aIRR 1.03, 95% CI 0.96– 1.10). South Asians had a lower risk of Crohn's disease (CD) (aIRR 0.66, 95% CI 0.60– 0.77), but a higher risk of ulcerative colitis (UC) (aIRR 1.47, 95% CI 1.34– 1.61). Chinese people had much lower rates of IBD (aIRR 0.24, 95% CI 0.20– 0.28), CD (aIRR 0.21, 95% CI 0.17– 0.26), and UC (aIRR 0.28, 95% CI 0.23– 0.25). Conclusion: Canadians of South Asian ethnicity had a similarly high risk of developing IBD compared to other Canadians, and a higher risk of developing UC, a finding distinct from the Chinese population. Our findings indicate the importance of genetic and environmental risk factors in people of Asian origin who live in the Western world. [ABSTRACT FROM AUTHOR]

Background: Advanced colorectal neoplasms (ACNs), including colorectal cancers (CRC) and high-risk adenomas (HRA), are detected in less than 20% of persons aged 50 years or older who undergo colonoscopy. We sought to derive personalized predictive models of risk of harbouring ACNs to improve colonoscopy wait times for high-risk patients and allocation of colonoscopy resources.Methods: We characterized colonoscopy indications, neoplasia risk factors and colonoscopy findings through chart review for consecutive individuals aged 50 years or older who underwent outpatient colonoscopy at The Ottawa Hospital (Ottawa, Canada) between April 1, 2008 and March 31, 2012 for non-life threatening indications. We linked patients to population-level health administrative datasets to ascertain additional historical predictor variables and derive multivariable logistic regression models for risk of harboring ACNs at colonoscopy. We assessed model discriminatory capacity and calibration and the ability of the models to improve colonoscopy specificity while maintaining excellent sensitivity for ACN capture.Results: We modelled 17 candidate predictors in 11,724 individuals who met eligibility criteria. The final CRC model comprised 8 variables and had a c-statistic value of 0.957 and a goodness-of-fit p-value of 0.527. Application of the models to our cohort permitted 100% sensitivity for identifying persons with CRC and > 90% sensitivity for identifying persons with HRA, while improving colonoscopy specificity for ACNs by 23.8%.Conclusions: Our multivariable models show excellent discriminatory capacity for persons with ACNs and could significantly increase colonoscopy specificity without overly sacrificing sensitivity. If validated, these models could allow more efficient allocation of colonoscopy resources, potentially reducing wait times for those at higher risk while deferring unnecessary colonoscopies in low-risk individuals. [ABSTRACT FROM AUTHOR]