Progression to colectomy in the era of biologics: A single center experience with pediatric ulcerative colitis.
Ontology highlight
ABSTRACT: Background/purpose
Clinical outcomes in pediatric ulcerative colitis (UC) in the era of biologic agents are poorly defined. We aimed to describe risk factors for colectomy in pediatric UC in the era of infliximab therapy.Methods
We reviewed 217 pediatric patients at Texas Children's Hospital with newly diagnosed UC between 2003 and 2015; 117 had a minimum of 5 years of follow-up. Extent of disease at diagnosis, medication exposure, the presence of extraintestinal manifestations (EIMs), and need for surgery were noted.Results
Average length of follow up was 5.02 ± 2.27 years. Forty-two percent presented with pancolitis. Infliximab was used in 39%, immunomodulators in 65%, and steroids in 89% of patients. EIMs occurred in 24.9% of patients. The cumulative rate of colectomy was 12.9% at 5 years. Children presenting as E2 (Paris Classification) and children prescribed oral steroid monotherapy at diagnosis progressed to surgery faster than any other group. Of the children who received infliximab, females and children less than 5 years old were less likely to respond to therapy.Conclusions
The natural course of pediatric UC remains aggressive despite the addition of infliximab to the standard of care and suggests a need for early aggressive clinical intervention.Level-of-evidence rating
Level IV.
SUBMITTER: Ihekweazu FD
PROVIDER: S-EPMC7396289 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundUlcerative colitis (UC) patients failing medical management require colectomy. This study compares risk estimates for predictors of postoperative complication derived from administrative data against that of chart review and evaluates the accuracy of administrative coding for this population.MethodsHospital administrative databases were used to identify adults with UC undergoing colectomy from 1996-2007. Medical charts were reviewed and regression analyses comparing chart versus administrative data were performed to assess the effect of age, emergent operation, and Charlson comorbidities on the occurrence of postoperative complications. Sensitivity, specificity, and positive/negative predictive values of administrative coding for identifying the study population, Charlson comorbidities, and postoperative complications were assessed.ResultsCompared to chart review, administrative data estimated a higher magnitude of effect for emergent admission (OR 2.52 [95% CI: 1.80-3.52] versus 1.49 [1.06-2.09]) and Charlson comorbidities (OR 2.91 [1.86-4.56] versus 1.50 [1.05-2.15]) as predictors of postoperative complications. Administrative data correctly identified UC and colectomy in 85.9% of cases. The administrative database was 37% sensitive in identifying patients with???1Charlson comorbidity. Restricting analysis to active comorbidities increased the sensitivity to 63%. The sensitivity of identifying patients with at least one postoperative complication was 68%; restricting analysis to more severe complications improved the sensitivity to 84%.ConclusionsAdministrative data identified the same risk factors for postoperative complications as chart review, but overestimated the magnitude of risk. This discrepancy may be explained by coding inaccuracies that selectively identifying the most serious complications and comorbidities.
| S-EPMC3432603 | biostudies-literature
Project description:This project used glycomics approach to study the N-glycan present at the intestinal mucosal-luminal interface of pediatric UC patients.
2022-03-01 | PXD026327 | Pride
Project description:BACKGROUND:Ulcerative colitis (UC) is a chronic autoimmune inflammation of the colon. The condition significantly decreases quality of life and generates a substantial economic burden for healthcare payers, patients and the society in which they live. Some patients require chronic pharmacotherapy, and access to novel biologic drugs might be crucial for long-term remission. The analyses of cost-effectiveness for biologic drugs are necessary to assess their efficiency and provide the best available drugs to patients. OBJECTIVE:Our aim was to collect and assess the quality of economic analyses carried out for biologic agents used in the treatment of UC, as well as to summarize evidence on the drivers of cost-effectiveness and evaluate the transferability and generalizability of conclusions. METHODS:A systematic database review was conducted using MEDLINE (via PubMed), EMBASE, Cost-Effectiveness Analysis Registry and CRD0. Both authors independently reviewed the identified articles to determine their eligibility for final review. Hand searching of references in collected papers was also performed to find any relevant articles. The reporting quality of economic analyses included was evaluated by two reviewers using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We reviewed the sensitivity analyses in cost-effectiveness analyses to identify the variables that may have changed the conclusions of the study. Key drivers of cost-effectiveness were selected by identifying uncertain parameters that caused the highest change of the results of the analyses compared with base-case results. RESULTS:Of the 576 identified records, 87 were excluded as duplicates and 16 studies were included in the final review; evaluations for Canada, the UK and Poland were mostly performed. The majority of the evaluations revealed were performed for infliximab (approximately 75% of total volume); however, some assessments were also performed for adalimumab (50%) and golimumab (31%). Only three analyses were conducted for vedolizumab, whereas no relevant studies were found for etrolizumab and tofacitinib. The reporting quality of the included economic analyses was assessed as high, with an average score of 21 points per 24 maximum possible (range 14-23 points according to the ISPOR CHEERS statement checklist). In the case of most analyses, quality-adjusted life-years were used as a clinical outcome, and endpoints such as remission, response and mucosal healing were less common. The higher clinical effectiveness (based on response rates) of biological treatment over non-biological treatments was presented in revealed analyses. The incremental cost-utility ratios for biologics, compared with standard care, varied significantly between the studies and ranged from US$36,309 to US$456,979. The lowest value was obtained for infliximab and the highest for the treatment scheme including infliximab 5 mg/kg and infliximab 10 mg/kg + adalimumab. The change of utility weights and clinical parameters had the most significant influence on the results of the analysis; the variable related to surgery was the least sensitive. CONCLUSIONS:Limited data on the cost-effectiveness of UC therapy were identified. In the majority of studies, the lack of cost-effectiveness was revealed for biologics, which was associated with their high costs. Clinical outcomes are transferable to other countries and could be generalized; however, cost inputs are country-specific and therefore limit the transferability and generalizability of conclusions. The key drivers and variables that showed the greatest effect on the analysis results were utility weights and clinical parameters.
| S-EPMC5840213 | biostudies-literature
Project description:ObjectivePrimary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. In childhood, PAI is usually caused by monogenic diseases. Although congenital adrenal hyperplasia (CAH) is the most common cause of childhood PAI, numerous non-CAH genetic causes have also been identified.MethodsPatients aged 0-18 years and diagnosed with PAI between 1998 and 2019 in a tertiary care hospital were retrospectively evaluated. After the etiologic distribution was determined, non-CAH PAI patients were evaluated in detail.ResultsSeventy-three PAI patients were identified. The most common etiology was CAH (69.9%, n=51). Non-CAH etiologies accounted for 30.1% (n=22) and included adrenoleukodystrophy (ALD; n=8), familial glucocorticoid deficiency (n=3), Triple A syndrome (n=5), autoimmune adrenalitis (n=1), adrenal hypoplasia congenital (n=1), IMAGe syndrome (n=1), and other unknown etiologies (n=3). The median age at the time of AI diagnosis for non-CAH etiologies was 3.52 (0.03-15.17) years. The most frequent symptoms/clinical findings at onset were hyperpigmentation of skin (81.8%), symptoms of hypoglycemia (40.9%), and weakness/fatigue (31.8%). Hypoglycemia (50.0%), hyponatremia (36.4%) and hyperkalemia (22.7%) were prominent biochemical findings. Diagnosis of specific etiologies were proven genetically in 13 of 22 patients. A novel p.Q301* hemizygous frameshift mutation of the DAX1 gene was identified in one patient.ConclusionEtiology was determined in 86.3% of children with non-CAH PAI through specific clinical and laboratory findings with/ without molecular analysis of candidate genes. ALD was the most common etiology. Currently, advanced molecular analysis can be utilized to establish a specific genetic diagnosis for PAI in patients who have no specific diagnostic features.
| S-EPMC7947721 | biostudies-literature
Project description:Ulcerative colitis (UC) can be treated with surgery or medications. Patients often must choose between long-term immunosuppressant therapy or total colectomy. Whether one of these treatment approaches has a mortality benefit is uncertain.To determine whether patients with advanced UC treated with elective colectomy have improved survival compared with those treated with medical therapy.Retrospective matched cohort study.Data from all 50 states for Medicaid beneficiaries (2000 to 2005), Medicare beneficiaries (2006 to 2011), and dual-eligible persons (2000 to 2011).830 patients with UC pursuing elective colectomy and 7541 matched patients with UC pursuing medical therapy.The primary outcome was time to death. Cox proportional hazards models were used to compare the survival of patients with advanced UC treated with elective colectomy or medical therapy. The models controlled for significant comorbid conditions through matched and adjusted analysis.The mortality rates associated with elective surgery and medical therapy were 34 and 54 deaths per 1000 person-years, respectively. Elective colectomy was associated with improved survival compared with long-term medical therapy (adjusted hazard ratio [HR], 0.67 [95% CI, 0.52 to 0.87]), although this result did not remain statistically significant in all sensitivity analyses. Post hoc analysis by age group showed improved survival with surgery in patients aged 50 years or older with advanced UC (HR, 0.60 [CI, 0.45 to 0.79]; P = 0.032 for age-by-treatment interaction).Retrospective nonrandomized analysis is subject to residual confounding. The source cohort was derived from different databases throughout the study. Sensitivity and secondary analyses had reduced statistical power.Elective colectomy seemed to be associated with improved survival relative to medical therapy among patients aged 50 years or older with advanced UC.National Institutes of Health and Agency for Healthcare Research and Quality.
| S-EPMC4925099 | biostudies-literature
Project description:IntroductionThe Center for Medicare and Medicaid Services established 30-day readmission rate as a key metric in measuring high-value, cost-conscious care; therefore, our aim is to develop a risk score for 30-day readmission in ulcerative colitis (UC) patients undergoing colectomy or proctectomy.MethodsThis study used data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant user file (2011-2015). Patients with UC undergoing colectomy or proctectomy were identified using ICD-9, 10, and CPT codes. Stepwise multivariate analyses were used to determine risk factors associated with readmission including pre-operative conditions, laboratory results, operative variables, and post-operative complications. For readmission risk score assessment, a weighted logistic regression model was built and validated using ACS NSQIP 2011-2014 and 2015 data, respectively.ResultsA total of 4797 patients were included with 963 (20%) patients readmitted within 30 days. Potentially modifiable risk factors included deep vein thrombosis, pulmonary embolism, renal insufficiency, wound infection, urinary tract infection, sepsis/septic shock, and pre-existing congestive heart failure. Ten percent of patients with a risk score between 0 and 9 were readmitted, 18.5% with a score between 10 and 19, 52.2% with a score between 20 and 29, and 59.6% in patients with a risk score >29.ConclusionsMultiple potentially preventable risk factors are associated with 30-day readmission following colectomy or proctectomy in UC patients. Higher risk scores are associated with increased risk of unplanned readmission.
| S-EPMC6092348 | biostudies-literature
Project description:BACKGROUND:Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that in children unlike in adults shows no sex predilection. FMD is often underdiagnosed, and its pathophysiology is unclear. Delayed diagnosis may lead to refractory hypertension and decreases the chance of successful treatment. Doppler ultrasound (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and catheter-based angiography (angiography) are currently used to help make a clinicoradiological diagnosis of FMD. The main aim of the study was to compare the efficacy of imaging modalities which can allow for earlier and improved detection. Furthermore, an anatomical mapping of the location of lesions can help determine the best treatment modalities. METHODS:All patients with non-syndromic non-inflammatory renovascular hypertension were recruited from the Nephrology Department at the Children's Hospital of Philadelphia (CHOP) and enrolled in the U.S. FMD Registry maintained at the University of Michigan. Clinical presentation and imaging findings on US, CT, and MRI of children diagnosed with FMD were evaluated. RESULTS:Mean age at diagnosis was 7?±?4.9 years (4 months-17 years). Family history of hypertension (HTN) (52%), FMD (8.7%), Caucasian (60%), headache (48%), and HTN (80%) were the most prevalent symptom and sign at presentation. Bruits were 100% specific for renal artery stenosis (RAS) diagnosis but were heard in the minority of patients (3 patients, 12%). FMD was mainly unifocal within a single site (68%) or multiple sites (28%) and involved the main or first order renal branch in about 68% of children. Isolated distal lesions beyond the second order branches were found in about 25% of children. US imaging was significantly less sensitive than angiography (28%, p?=?0.003). MRA had a better sensitivity (62.5%, p?=?0.3) than US. Overall, CTA had the best sensitivity (84.2%, p?=?0.4) compared to angiography; however, only angiography showed distal vessel disease. CONCLUSIONS:Limitations of the study include the sample size and biases-only patients diagnosed with FMD were included in this study and most patients were referred to a pediatric nephrologist for unexplained hypertension. Angiography should be performed as part of the initial work-up of any child suspected of having renovascular FMD, regardless of the findings seen on US, MRA, or CTA.
| S-EPMC6082421 | biostudies-literature
Project description:BackgroundThe role of mitochondria in cancer is poorly understood. Ulcerative colitis (UC) is an inflammatory bowel disease that predisposes to colorectal cancer and is an excellent model to study tumor progression. Our goal was to characterize mitochondrial alterations in UC tumorigenesis.MethodsNondysplastic colon biopsies from UC patients with high-grade dysplasia or cancer (progressors; n = 9) and UC patients dysplasia free (nonprogressors; n = 9) were immunostained for cytochrome C oxidase (COX), a component of the electron transport chain, and were quantified by multispectral imaging. For six additional progressors, nondysplastic and dysplastic biopsies were stained for COX and additional mitochondrial proteins including PGC1α, the master regulator of mitochondrial biogenesis. Mitochondrial DNA (mtDNA) copy number was determined by quantitative polymerase chain reaction. Generalized estimating equations with two-sided tests were used to account for correlation of measurements within individuals.ResultsNondysplastic biopsies of UC progressors showed statistically significant COX loss compared with UC nonprogressors by generalized estimating equation (-18.5 units, 95% confidence interval = -12.1 to -24.9; P < .001). COX intensity progressively decreased with proximity to dysplasia and was the lowest in adjacent to dysplasia and dysplastic epithelium. Surprisingly, COX intensity was statistically significantly increased in cancers. This bimodal pattern was observed for other mitochondrial proteins, including PGC1α, and was confirmed by mtDNA copy number.ConclusionsMitochondrial loss precedes the development of dysplasia, and it could be used to detect and potentially predict cancer. Cancer cells restore mitochondria, suggesting that mitochondria are needed for further proliferation. This bimodal pattern might be driven by transcriptional regulation of mitochondrial biogenesis by PGC1α.
| S-EPMC3748006 | biostudies-literature
Project description:OBJECTIVES:Differentiating ulcerative colitis (UC) and Crohn disease (CD) can be clinically challenging, especially in children. Granulomatous inflammation has traditionally been attributed to CD. Crypt-associated giant cells and granulomas, however, have been observed in colonic biopsies of patients with UC. This phenomenon has not been described in the upper gastrointestinal (UGI) tract with UC. METHODS:Seven pediatric patients with UC with granulomatous UGI (gUGI) lesions were identified. Diagnosis of UC was based on symptoms, clinical course, laboratory results, imaging, and endoscopy. We compared the gUGI patients to a large cohort of pediatric patients with UC (n?=?149). RESULTS:All fully evaluated cases were associated with bloody diarrhea and moderate to severe pancolitis. Gastric and/or duodenal biopsies demonstrated giant cells or granulomas near gland destruction. Small bowel imaging did not reveal any involvement. The majority of cases responded to standard medical therapies, except for 2 patients (28.6%) who required total colectomy. Acute severe, refractory colitis (ie, colectomy within 1 month of presentation) was significantly more common in the gUGI group than the large pediatric UC group (28.6% vs 1.3%, Fisher exact P?=?0.01). CONCLUSIONS:This is the first report of pediatric UC-associated granulomatous inflammation in the UGI tract. We speculate that these lesions represent extracolonic manifestations of intense colonic disease. These atypical findings expand the diagnostic considerations that should be incorporated during the differentiation between UC and CD in the pediatric age group.
| S-EPMC5866164 | biostudies-literature
Project description:Background: Data on serum infliximab concentrations during induction in pediatric ulcerative colitis are limited. The study aim is to evaluate the relationship between serum infliximab concentrations during induction and short-term clinical remission in children with ulcerative colitis. Methods: We carried out a prospective, multi-center cohort study in pediatric patients with ulcerative colitis. Serum infliximab concentrations were collected at peak dose #1, week 1, trough pre-dose #2, and trough pre-dose #3. Infliximab dosing was left to investigator discretion. Clinical remission was defined by pediatric ulcerative colitis activity index <10 at week 8. Results: Twenty-four of thirty-four subjects (71%) achieved clinical remission at week 8. The median infliximab concentrations were 33.0 μg/mL (interquartile range: 26.5-52.1 μg/mL) pre-dose #2 and 22.5 μg/mL (interquartile range:15.9-32.3 μg/mL) pre-dose #3. Trough pre-dose #2 infliximab concentration yielded area under receiver operator characteristic curve 0.7, 95% CI: 0.5-0.9 in predicting week 8 clinical remission; a cut-off of 33.0 μg/mL yielded 62.5% sensitivity, 66.7% specificity. Trough pre-dose #3 infliximab concentrations were lower for subjects <10 years compared to ≥ 10 years [median 15.9 μg/mL, interquartile range (IQR) 8.5-21.8 μg/mL vs. 27.7 μg/mL, IQR 17.2-46.7 μg/mL, p = 0.01] and correlated with baseline weight (Spearman's rank correlation coefficient 0.45, p = 0.01). The median half-life following first IFX dose was 6.04 days (IQR 5.3-7.9 days). Conclusions: Infliximab concentrations ≥33 μg/mL prior to the second dose were associated with week 8 clinical remission. As young age and low body weight impact infliximab concentration, prospective studies with proactive adjustment in pediatric patients with ulcerative colitis should be carried out. Clinicians caring for children with UC should diligently adjust and monitor infliximab to optimize response.
| S-EPMC8358797 | biostudies-literature