KT Park, MD

Abstract

BACKGROUND AND AIMS: Tumor Necrosis Factor inhibitors (TNFi), including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease (PCD) therapy; however, non-response and loss of response is common. As combination therapy with methotrexate may improve response, we performed a multi-center, randomized, double-blind, placebo-controlled pragmatic trial to compare TNFi with oral methotrexate to TNFi monotherapy.METHODS: PCD patients initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies (ADA) and patient reported outcomes (PROs) of pain interference and fatigue. Adverse events (AEs) and Serious AEs (SAEs) were collected.RESULTS: Of 297 participants (mean age 13.9 years, 35% female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (HR 0.69, 95% CI 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (HR 0.93, 95% CI 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (HR 0.40, 95% CI 0.19-0.81). A trend towards lower ADA development in the combination therapy arm was not significant. [(infliximab OR 0.72 (0.49-1.07); adalimumab OR 0.71 (0.24-2.07)]. No differences in PROs were observed. Combination therapy resulted in more AEs but fewer SAEs.CONCLUSIONS: Among adalimumab but not infliximab initiators, PCD patients treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile.

View details for DOI 10.1053/j.gastro.2023.03.224

View details for PubMedID 37004887

Abstract

Systemic steroid exposure, while useful for the treatment of acute flares in inflammatory bowel disease (IBD), is associated with an array of side effects that are particularly significant in children. Technical advancements have enabled locoregional intraarterial steroid delivery directly into specific segments of the gastrointestinal tract, thereby maximizing tissue concentration while limiting systemic exposure. We investigated the feasibility of intraarterial steroid administration into the bowel in a cohort of nine pediatric patients who had IBD. This treatment approach provided symptom relief in all patients, with sustained relief (>2 weeks) in seven out of nine; no serious adverse effects occurred in any patient. In addition, we identified patterns of vascular morphologic changes indicative of a vasculopathy within the mesenteric circulation of inflamed segments of the bowel in pediatric patients with Crohn's disease, which correlated with disease activity. An analysis of publicly available transcriptomic studies identified vasculitis-associated molecular pathways activated in the endothelial cells of patients with active Crohn's disease, suggesting a possible shared transcriptional program between vasculitis and IBD. Intraarterial corticosteroid treatment is safe and has the potential to be widely accepted as a locoregional approach for therapy delivery directly into the bowel; however, this approach still warrants further consideration as a short-term "bridge" between therapy transitions for symptomatic IBD patients with refractory disease, as part of a broader steroid-minimizing treatment strategy.

View details for DOI 10.3390/jcm12062386

View details for PubMedID 36983386

Abstract

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.

View details for DOI 10.1016/S2468-1253(23)00003-1

View details for PubMedID 36871566

Abstract

Etrolizumab, a humanized anti-7 antibody, has not been studied in children. Here, we evaluate the pharmacokinetics, pharmacodynamics, and safety of etrolizumab in children with inflammatory bowel disease.Patients age 4 to 17 years with moderately to severely active ulcerative colitis or Crohn's disease were randomized 1:1 to receive 1.5mg/kg of etrolizumab subcutaneously every 4 weeks (q4w) or 3.0mg/kg every 8 weeks (q8w) for 16 weeks in this open-label phase 1 trial. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed.Of the 24 patients treated, 21 completed the study. In the groups of 1.5mg/kg q4w and 3.0mg/kg q8w, respectively, mean (SD) maximum concentration (Cmax) was 9.8 (4.86) g/mL and 18.1 (6.25) g/mL; and mean (SD) area under the curve within a dosing interval (AUCtau) was 167 (86.9) and 521 (306) gday/mL after the last dose. The Cmax increased dose proportionally. The AUC over an 8-week period was slightly higher in the 3.0mg/kg q8w dose group. Median half-life was similar for both dosing regimens. Median numbers of free 7high gut-homing T and B cell subsets declined below 10% of baseline, confirming 7 target engagement and complete/near-complete receptor occupancy. Adverse events were consistent with the safety profile in adults. Approximately 60% of patients achieved a clinical response.Etrolizumab showed a dose-proportional increase in Cmax and a slightly greater than dose-proportional increase in AUCtau. Both regimens achieved complete/near-complete 7 receptor occupancy, with a similar relationship to concentration as adults. Etrolizumab was well tolerated and demonstrated clinical activity in children.

View details for DOI 10.1093/ibd/izab275

View details for PubMedID 34849918

View details for PubMedCentralID PMC9434437

Abstract

BACKGROUND: Patients with Crohn's disease (CD) may develop fibrostenotic strictures. No currently available therapies prevent or treat fibrostenotic CD (FCD), making this a critical unmet need.AIM: To compare health outcomes and resource utilisation between CD patients with and without fibrostenotic disease.METHODS: Patients aged 18 years with FCD and non-FCD between 30 October 2015 and 30 September 2018 were identified in the Truven MarketScan Commercial Claims and Encounters Database. We conducted 1:3 nearest neighbour propensity score matching on age, sex, malnutrition, payer type, anti-tumour necrosis factor use, and Charlson Comorbidity Index score. Primary outcomes up to 1 year from the index claim were 1 hospitalisation, 1 procedure, 1 surgery, and steroid dependency (>100 day supply). Associations between FCD diagnosis and outcomes were estimated with a multivariable logistic regression model. This study was exempt from institutional review board approval.RESULTS: Propensity score matching yielded 11 022 patients. Compared with non-FCD, patients with FCD had increased likelihood of hospitalisations (17.1% vs 52.4%; p<0.001), endoscopic procedures (4.4% vs 8.6%; p<0.001), IBD-related surgeries (4.7% vs 9.1%; p<0.001), steroid dependency (10.0% vs 15.7%; p<0.001), and greater mean annual costs per patient ($47 575 vs $77609; p<0.001). FCD was a significant risk factor for 1 hospitalisation (adjusted OR (aOR), 6.1), 1 procedure (aOR, 2.1), 1 surgery (aOR, 2.0), and steroid dependency (aOR, 1.7).CONCLUSIONS: FCD was associated with higher risk for hospitalisation, procedures, abdominal surgery, and steroid dependency. Patients with FCD had a greater mean annual cost per patient. FCD represents an ongoing unmet medical need.

View details for DOI 10.1136/bmjgast-2021-000781

View details for PubMedID 34930755

Abstract

BACKGROUND: Indigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model.METHODS: This open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500mg/day or 1.5g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression.RESULTS: Ten of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN.CONCLUSION: IN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation.TRIAL REGISTRATION NUMBER: NCT02442960.

View details for DOI 10.1136/bmjgast-2021-000813

View details for PubMedID 34969665

Abstract

AIMS: In order to better predict the pharmacokinetics (PK) of antibodies in children, and to facilitate dose optimization of antibodies in pediatric patients, there is a need to develop systems PK models that integrate ontogeny related changes in human physiological parameters.METHODS: A population-based physiological-based PK (PBPK) model to characterize antibody PK in pediatrics has been developed, by incorporating age-related changes in body weight, organ weight, organ blood flow rate, and interstitial volumes in a previously published platform model. The model was further used to perform Monte Carlo simulations to investigate clearance vs. age and dose-exposure relationship for infliximab.RESULTS: By estimating only one parameter and associated interindividual variability, the model was able to characterize clinical PK of infliximab from two pediatric cohorts (n=141, 4-19 years) reasonably well. Model simulations demonstrated that only 50% of children reached desired trough concentrations when receiving FDA-labelled dosing regimen for infliximab, suggesting that higher doses and/or more frequent dosing are needed to achieve target trough concentrations of this antibody.CONCLUSION: The pediatric PBPK model presented here can serve as a framework to characterize the PK of antibodies in pediatric patients. The model can also be applied to other protein therapeutics to advance precision medicine paradigm and optimize antibody dosing regimens in children.

View details for DOI 10.1111/bcp.14963

View details for PubMedID 34189743

View details for Web of Science ID 000619875100076

Abstract

OBJECTIVES: Endoscopic remission has become a standard treatment target in inflammatory bowel disease (IBD). It is unclear how widely this practice has been adopted amongst pediatric gastroenterology providers. This study determines the frequency of repeat endoscopy in pediatric IBD and evaluates for predictive baseline characteristics of providers.METHODS: We developed a cross-sectional survey which was distributed via three national email listservs to pediatric gastroenterology providers. We obtained baseline characteristics of respondents and assessed motivations and barriers for the practice of repeat endoscopy compared to none.RESULTS: 238 unique respondents completed the online survey. Response rate was 11% (238 of 2300 possible participants). The majority practice in an academic setting (77%) and reported participation in ImproveCareNow (63%). Overall, 65% of respondents perform repeat endoscopy to assess for endoscopic remission in pediatric IBD as part of routine clinical practice. 56% reported repeat endoscopy as individuals in the absence of a departmental protocol. "Symptoms are not sufficient to follow IBD patients" was reported by 82% of those who repeat endoscopy; conversely, "I perform endoscopy based on clinical, biomarker, and/or imaging trends" was reported by 81% of those who do not repeat endoscopy. The establishment of a pediatric-specific guideline was most commonly reported to change current practice, based on rank-order scoring.CONCLUSION: A majority of representative providers repeat endoscopy to assess for endoscopic remission in pediatric IBD. Fewer years in practice favored repeating endoscopy. The need for North American pediatric guidelines with pediatric-specific evidence to support the long term benefits of endoscopic remission are highlighted in this study.

View details for DOI 10.1097/MPG.0000000000003100

View details for PubMedID 33633082

Abstract

The incidence of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) is higher than in the general pediatric population. However, reports of IBD in the systemic JIA (sJIA) subtype are limited. We sought to characterize sJIA patients diagnosed with IBD and to identify potential contributing risk factors.Using an internationally distributed survey, we identified 16 sJIA patients who were subsequently diagnosed with IBD (sJIA-IBD cohort). 522 sJIA patients without IBD were identified from the CARRA Legacy Registry and served as the sJIA-only cohort for comparison. Differences in demographic, clinical characteristics and therapy were assessed using chi-square test, Fisher's exact test, t-test, and univariate and multivariate logistic regression as appropriate.75% of sJIA-IBD patients had a persistent sJIA course; 25% had a history of MAS. sJIAIBD subjects were older at sJIA diagnosis, more often non-White, had a higher rate of IBD family history, and were more frequently treated with etanercept or canakinumab compared to sJIA-only subjects. 69% of sJIA-IBD patients successfully discontinued sJIA medications following IBD diagnosis, and sJIA symptoms resolved in 9/12 patients treated with TNF- inhibitors.IBD in the setting of sJIA is a rare occurrence. The favorable response of sJIA symptoms to therapeutic TNF- inhibition suggests that the sJIA-IBD cohort may represent a mechanistically distinct sJIA subgroup. Our study highlights the importance of maintaining a high level of suspicion for IBD when gastrointestinal involvement occurs in sJIA patients and the likely broad benefit of TNF- inhibition in those cases.

View details for DOI 10.3899/jrheum.200230

View details for PubMedID 32541073

Abstract

Biologic agents including infliximab are effective but costly therapies in the management of inflammatory bowel disease (IBD). Home infliximab infusions are increasingly payer-mandated to minimize infusion-related costs. This study aimed to compare biologic medication use, health outcomes, and overall cost of care for adult and pediatric patients with IBD receiving home vs office- vs hospital-based infliximab infusions.Longitudinal patient data were obtained from the Optum Clinformatics Data Mart. The analysis considered all patients with IBD who received infliximab from 2003 to 2016. Primary outcomes included nonadherence (2 infliximab infusions over 10 weeks apart in 1 year) and discontinuation of infliximab. Secondary outcomes included outpatient corticosteroid use, follow-up visits, emergency room visits, hospitalizations, surgeries, and cost outcomes (out-of-pocket costs and annual overall cost of care).There were 27,396 patients with IBD (1,839 pediatric patients). Overall, 5.7% of patients used home infliximab infusions. These patients were more likely to be nonadherent compared with both office-based (22.2% vs 19.8%; P = .044) and hospital-based infusions (22.2% vs 21.2%; P < .001). They were also more likely to discontinue infliximab compared with office-based (44.7% vs 33.7%; P < .001) or hospital-based (44.7% vs 33.4%; P < .001) infusions. On Kaplan-Meier analysis, the probabilities of remaining on infliximab by day 200 of therapy were 64.4%, 74.2%, and 79.3% for home-, hospital-, and office-based infusions, respectively (P < .001). Home infliximab patients had the highest corticosteroid use (cumulative corticosteroid days after IBD diagnosis: home based, 238.2; office based, 189.7; and hospital based, 208.5; P < .001) and the fewest follow-up visits. Home infusions did not decrease overall annual care costs compared with office infusions ($49,149 vs $43,466, P < .001).In this analysis, home infliximab infusions for patients with IBD were associated with suboptimal outcomes including higher rates of nonadherence and discontinuation of infliximab. Home infusions did not result in significant cost savings compared with office infusions.

View details for DOI 10.14309/ajg.0000000000000750

View details for PubMedID 32701731

Abstract

To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System.ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers.The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks were developed to enable centers to monitor and improve the quality of their data.There was a pattern of improvement across measures of data quality. The proportion of visits with complete critical data increased from 72 percent to 82 percent. The percent of registered patients improved from 59 percent to 83 percent. Of three additional measures of data consistency and timeliness, one improved performance from 42 percent to 63 percent. Performance declined on one measure due to changes in network documentation practices and maturation. There was variation among care centers in data quality.A quality improvement based approach to data quality monitoring and improvement is feasible and effective.

View details for DOI 10.5334/egems.262

View details for PubMedID 31646151

View details for PubMedCentralID PMC6777196

View details for DOI 10.14309/01.ajg.0000578116.03611.38

View details for Web of Science ID 000480731700012

View details for PubMedID 30849315

Abstract

Eating disorders are one of the most common chronic conditions in adolescents. The clinical symptoms can mimic those of other chronic diseases including gastrointestinal and endocrine disorders. However, an eating disorder can coexist with another chronic disease, making the diagnosis and management of both conditions challenging. This Review describes what is known about eating disorders in adolescents with chronic gastrointestinal and endocrine diseases, focusing on coeliac disease, inflammatory bowel disease, diabetes, and thyroid disorders. The prevalence and onset of each condition during adolescence is discussed, followed by a description of the associations among the conditions and eating disorders. We also discuss management challenges posed by the coexistence of the two conditions. When both diseases coexist, a multidisciplinary approach is often needed to address the additional complexities posed.

View details for PubMedID 30638841

Abstract

Sex-based treatment disparities occur in many diseases. Women undergo fewer procedural interventions, and their care is less consistent with guideline-based therapy. There is limited research exploring sex-based differences in ulcerative colitis treatment. We hypothesized that women are less likely to be treated with strategies consistent with long-term disease remission, including surgery and maintenance medications.The aim of this study was to determine if patient sex is associated with choice of treatment strategy for ulcerative colitis.This is a retrospective cohort analysis.Data were gathered from a large commercial insurance claims database (Truven MarketScan) from 2007 to 2015.We identified a cohort of 38,851 patients newly diagnosed with ulcerative colitis, aged 12 to 64 years with at least 1 year of follow-up.The primary outcomes measured were the differences between male and female patients in 1) rates and types of index ulcerative colitis operations, 2) rates and types of ulcerative colitis medication prescriptions, and 3) rates of opioid prescriptions.Men were more likely to undergo surgical treatment for ulcerative colitis (2.94% vs 1.97%, p < 0.001, OR 1.51, p < 0.001). The type of index operation performed did not vary by sex. Men were more likely to undergo treatment with maintenance medications, including biologic (12.4% vs 10.2%, p < 0.001, OR 1.22, p < 0.001), immunomodulatory (16.3% vs 14.9%, p < 0.001, OR 1.08, p = 0.006), and 5-aminosalicylate medications (67.0% vs 63.2%, p < 0.001, OR 1.18, p < 0.001). Women were more likely to undergo treatment with rescue therapies and symptomatic control with corticosteroids (55.5% vs 54.0%, p = 0.002, OR 1.07, p = 0.002) and opioids (50.2% vs 45.9%, p < 0.001, OR 1.17, p < 0.001).Claims data lack clinical characteristics acting as confounders.Men with ulcerative colitis were more likely to undergo treatment consistent with long-term remission or cure, including maintenance medications and definitive surgery. Women were more likely to undergo treatment consistent with short-term symptom management. Further studies to explore underlying mechanisms of sex-related differences in ulcerative colitis treatment strategies and disease trajectories are warranted. See Video Abstract at http://links.lww.com/DCR/Axxx.

View details for PubMedID 30762599

View details for DOI 10.1016/j.cgh.2019.08.052

View details for PubMedID 31499250

Abstract

Patients with inflammatory bowel disease and their physicians must navigate ever-increasing options for treatment. The aim of this study was to elucidate the key drivers of treatment decision-making in inflammatory bowel disease.We conducted qualitative semi-structured in-person interviews of 20 adult patients undergoing treatment for inflammatory bowel disease at an academic medical centre who either recently initiated biologic therapy or underwent an operation or surgical evaluation. Interviews were audio-recorded, transcribed verbatim, iteratively coded, and discussed to consensus by five researchers. We used thematic analysis to explore factors influencing decision-making.Four major themes emerged as key drivers of treatment decision-making: perceived clinical state and disease severity, the patient-physician relationship, knowledge, attitudes, and beliefs about treatment options, and social isolation and stigma. Patients described experiencing a clinical turning point as the impetus for proceeding with a previously undesired treatment such as infusion medication or surgery. Patients reported delays in care or diagnosis, inadequate communication with their physicians, and lack of control over their disease management. Patients often stated that they considered surgery to be the treatment of last resort, which further compounded the complexity of making treatment decisions.Patients described multiple barriers to making informed and collaborative decisions about treatment, especially when considering surgical options. Our study reveals a need for more comprehensive communication between the patient and their physician about the range of medical and surgical treatment options. We recommend a patient-centred approach toward the decision-making process that accounts for patient decision-making preferences, causes of social stress, and clinical status. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/codi.14759

View details for PubMedID 31295766

View details for DOI 10.1001/jamainternmed.2019.0213

View details for PubMedID 31107504

Abstract

Data on the incidence of inflammatory bowel disease (IBD) by age group are available in countries outside of the United States or localized populations within the United States. We aimed to estimate the incidence rates (IRs) of IBD by age group using a US multiregional data set.We used the Optum Research Database to identify incident IBD patients with a disease-free interval of 1.5 years between 2005 and 2015. Overall and age-specific IRs were calculated for 4 different age groups: pediatric (0-17 years), young adult (18-25 years), adult (26-59 years), elderly (>60 years). Time trends of incidence were evaluated in each age group. Perianal phenotype (in Crohn's disease [CD]) was also compared.The mean IR for the cohort (n = 60,247) from 2005 to 2015 was 37.5/100,000. The IR was highest in adult and elderly cohorts (36.4 and 36.7/100,000 respectively). In the adult and elderly groups, the IR for UC was higher than that for CD, whereas the opposite was true in the pediatric and young adult groups. The IR increased over the 10-year study period for all age groups (time trends P < 0.001). The elderly group had less perianal disease than the adult group (20.8 vs 22.3%, respectively; P < 0.05).In one of the most comprehensive evaluations of the incidence of IBD in the United States, we found an incidence rate similar to those of other national populations. We also confirmed differences of specific IBD phenotypes based on age groups, with lower rates of perianal disease in the elderly.

View details for PubMedID 31095681

Abstract

The Crohn's & Colitis Foundation's Cost of Inflammatory Bowel Disease (IBD) Care Initiative seeks to quantify the wide-ranging health care costs affecting patients living with IBD. We aimed to (1) describe the annualized direct and indirect costs of care for patients with Crohn's disease (CD) or ulcerative colitis (UC), (2) determine the longitudinal drivers of these costs, and (3) characterize the cost of care for newly diagnosed patients.We analyzed the Optum Research Database from the years 2007 to 2016, representing commercially insured and Medicare Advantage-insured patients in the United States. Inclusion for the study was limited to those who had continuous enrollment with medical and pharmacy benefit coverage for at least 24 months (12 months before through 12 months after the index date of diagnosis). The value of patient time spent on health care was calculated as number of workplace hours lost due to health care encounters multiplied by the patients' estimated average wage derived from the Bureau of Labor Statistics. Comparisons between IBD patients and non-IBD patients were analyzed based on demographics, health plan type, and length of follow-up. We used generalized linear models to estimate the association between total annual costs and various patient variables.There were 52,782 IBD patients (29,062 UC; 23,720 CD) included in the analysis (54.1% females). On a per-annual basis, patients with IBD incurred a greater than 3-fold higher direct cost of care compared with non-IBD controls ($22,987 vs $6956 per-member per-year paid claims) and more than twice the out-of-pocket costs ($2213 vs $979 per-year reported costs), with all-cause IBD costs rising after 2013. Patients with IBD also experienced significantly higher costs associated with time spent on health care as compared with controls. The burden of costs was most notable in the first year after initial IBD diagnosis (mean = $26,555). The study identified several key drivers of cost for IBD patients: treatment with specific therapeutics (biologics, opioids, or steroids); ED use; and health care services associated with relapsing disease, anemia, or mental health comorbidity.The costs of care for IBD have increased in the last 5 years and are driven by specific therapeutics and disease features. In addition, compared with non-IBD controls, IBD patients are increasingly incurring higher costs associated with health care utilization, out-of-pocket expenditures, and workplace productivity losses. There is a pressing need for cost-effective strategies to address these burdens on patients and families affected by IBD.

View details for DOI 10.1093/ibd/izz104

View details for PubMedID 31112238

Abstract

Unnecessary use of antibiotics is an increasing problem. In this study, we sought to determine the diagnostic accuracy of procalcitonin in predicting bacteremia in children with a central line and fever, and we sought to determine optimal cutoff values to maximize sensitivity and specificity. This is the largest study to date in which procalcitonin is examined as a predictive marker of bacteremia in pediatric patients with a central line and fever.We conducted a retrospective cohort study of children aged 0 to 23 years with a central line and fever of 38C who had procalcitonin and blood cultures drawn before initiation of antibiotics and had no other identified bacterial infection. Patients were also prospectively monitored via a custom-built electronic medical record dashboard for eligibility.There were 523 patients and >2500 procalcitonin values reviewed for eligibility. Of these, 169 (47%) patients and 335 blood cultures with procalcitonin were included. There were 94 (28%) positive bacterial blood cultures and 241 (72%) negative bacterial blood cultures. In bacteremic cultures, the mean procalcitonin level was 9.96 15.96 ng/mL, and the median procalcitonin level was 4.85 ng/mL (interquartile range 18.5). In nonbacteremic cultures, the mean procalcitonin level was 1.23 10.37 ng/mL, and the median procalcitonin level was 0.3 ng/mL (interquartile range 0.7). A receiver operating characteristic analysis indicated a procalcitonin level of 0.6 ng/mL as the best cutoff point that produced a sensitivity of 85.6% and a specificity of 65.7% (area under the curve 0.85).Procalcitonin is a sensitive biomarker in predicting bacteremia in children with a central line and fever.

View details for PubMedID 31097470

Abstract

Importance: Through prescription writing, dental clinicians are a potential source of initial opioid exposure and subsequent abuse for adolescents and young adults.Objective: To examine the association between index dental opioid prescriptions from dental clinicians for opioid-naive adolescents and young adults in 2015 and new persistent use and subsequent diagnoses of abuse in this population.Design, Setting, and Participants: This retrospective cohort study examined outpatient opioid prescriptions for patients aged 16 to 25 years in the Optum Research Database in 2015. Prescriptions were linked by National Provider Identifier number to a clinician category.Exposures: Individuals were included in the index dental opioid (opioid-exposed) cohort if they filled an opioid prescription from a dental clinician in 2015, had continuous health plan coverage and no record of opioid prescriptions for 12 months before receiving the prescription, and had 12 months of health plan coverage after receiving the prescription. Two age- and sex-matched opioid-nonexposed control individuals were selected for each opioid-exposed individual and were assigned a corresponding phantom prescription date.Main Outcomes and Measures: Receipt of an opioid prescription within 90 to 365 days, a health care encounter diagnosis associated with opioid abuse within 365 days, and all-cause mortality within 365 days of the index opioid or phantom prescription date.Results: Among 754002 individuals with continuous enrollment in 2015, 97462 patients (12.9%) received 1 or more opioid prescriptions, of whom 29791 (30.6%) received prescriptions supplied by a dental clinician. The opioid-exposed cohort included 14888 participants (7882 women [52.9%], 11273 white [75.7%], with mean [SD] age, 21.8 [2.4] years), and the randomly selected opioid-nonexposed cohort included 29776 participants (15764 women [52.9%], 20078 [67.4%] white, with mean [SD] age, 21.8 [2.4] years). Among the 14888 individuals in the index dental opioid cohort, 1021 (6.9%) received another opioid prescription 90 to 365 days later compared with 30 of 29776 (0.1%) opioid-nonexposed controls (adjusted absolute risk difference, 6.8%; 95% CI, 6.3%-7.2%), and 866 opioid-exposed individuals (5.8%) experienced 1 or more subsequent health care encounters with an opioid abuse-related diagnosis compared with 115 opioid-nonexposed controls (0.4%) (adjusted absolute risk difference, 5.3%; 95% CI, 5.0%-5.7%). There was only 1 death in each cohort.Conclusions and Relevance: The findings suggest that a substantial proportion of adolescents and young adults are exposed to opioids through dental clinicians. Use of these prescriptions may be associated with an increased risk of subsequent opioid use and abuse.

View details for PubMedID 30508022

View details for DOI 10.1016/j.jamcollsurg.2018.07.347

View details for Web of Science ID 000447760600318

Abstract

Background: Depression frequently co-occurs in patients with inflammatory bowel disease (IBD) and is a driver in health care costs and utilization.Aim: This study examined the associations between depression and total health care costs, emergency department (ED) visits, computed tomography (CT) scans during ED/inpatient visits, and IBD-related surgery among IBD patients.Methods: Our sample included 331,772 IBD patients from a national administrative claims database (Truven Health MarketScan Database). Gamma and Poisson regression analyses assessed differences related to depression controlling for key variables.Results: Approximately 16% of the IBD cohort was classified as having depression. Depression was associated with a $17,706 (95% CI [$16,892, 18,521]) increase in mean annual IBD-related health care costs and an increased incidence of ED visits (aIRR of 1.5; 95% CI [1.5, 1.6]). Among patients who had 1 ED/inpatient visits, depression was associated with an increased probability of receiving repeated CT scans (1-4 CT scans aOR of 1.6; 95% CI [1.5, 1.7]; 5 CT scans aOR 4.6; 95% CI [2.9, 7.3]) and increased odds of undergoing an IBD-related surgery (aOR of 1.2; 95% CI [1.1, 1.2]). Secondary analysis with a pediatric subsample revealed approximately 12% of this cohort was classified as having depression, and depression was associated with increased costs and incidence rates of ED visits and CT scans, but not IBD-related surgery.Conclusion: Quantifiable differences in healthcare costs and patterns of utilization exist among patients with IBD and depression. Integration of mental health services within IBD care may improve overall health outcomes and costs of care.

View details for PubMedID 30256923

Abstract

As clinicians have begun to provide targeted pharmacotherapy for children with inflammatory bowel disease (IBD), several ethical challenges have arisen. In this paper, we review 3 challenges related to applying a precision health approach to pediatric IBD populations: selection of a disease monitoring method, pharmacotherapy optimization, and economic considerations in clinical decision making.

View details for PubMedID 30242815

View details for Web of Science ID 000431387700019

Abstract

The primary aim of this Clinical Report by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition is to provide formal guidance to pediatric gastroenterologists and clinicians, health systems, and insurance payers regarding home- and office-based infusions for biologic therapies in pediatric inflammatory bowel disease (IBD). Patients in North America are increasingly denied coverage by payers based on "place of service" codes at hospital-based infusion units where the treating clinicians primarily provide care. A task force with topic expertise generated 8 best practice recommendations to ensure quality of care for pediatric patients with IBD receiving non-hospital based biologic infusions. Pragmatic considerations discussed in this report include patient safety, pediatric-trained nurse availability, care coordination, patient-centeredness, shared liability, administrative support, clinical governance, and costs of care.

View details for PubMedID 29324477

Abstract

Opioids are commonly prescribed for relief in inflammatory bowel disease (IBD). Emerging evidence suggests that adolescents and young adults are a vulnerable population at particular risk of becoming chronic opioid users and experiencing adverse effects.This study evaluates trends in the prevalence and persistence of chronic opioid therapy in adolescents and young adults with IBD in the United States.A longitudinal retrospective cohort analysis was conducted with the Truven MarketScan Database from 2007 to 2015. Study subjects were 15-29 years old with 2 IBD diagnoses (Crohn's: 555/K50; ulcerative colitis: 556/K51). Opioid therapy was identified with prescription claims within the Truven therapeutic class 60: opioid agonists. Persistence of opioid use was evaluated by survival analysis for patients who remained in the database for at least 3 years following index chronic opioid therapy use.In a cohort containing 93,668 patients, 18.2% received chronic opioid therapy. The annual prevalence of chronic opioid therapy increased from 9.3% in 2007 to 10.8% in 2015 (P < 0.01), peaking at 12.2% in 2011. Opioid prescriptions per patient per year were stable (approximately 5). Post hoc Poisson regression analyses demonstrated that the number of opioid pills dispensed per year increased with age and was higher among males. Among the 2503 patients receiving chronic opioid therapy and followed longitudinally, 30.5% were maintained on chronic opioid therapy for 2 years, and 5.3% for all 4 years.Sustained chronic opioid use in adolescents and young adults with IBD is increasingly common, underscoring the need for screening and intervention for this vulnerable population.

View details for PubMedID 29986015

Abstract

10.1093/ibd/izy205_video1izy205.video15799266615001.

View details for PubMedID 29931102

Abstract

Perioperative vedolizumab (VDZ) and anti-tumour necrosis factor (TNFi) therapies are implicated in causing post-operative complications in inflammatory bowel disease (IBD).To compare the risk of surgical site infections (SSIs) between VDZ- and TNFi-treated IBD patients in propensity-matched cohorts.The Optum Research Database was used to identify IBD patients who received VDZ or TNFi within 30days prior to abdominal surgery between January 2015 and December 2016. The date of IBD-related abdominal surgery was defined as the index date. SSIs were determined by ICD-9/10 and CPT codes related to superficial wound infections or deep organ space infections after surgery. Propensity score 1:1 matching established comparable cohorts based on VDZ or TNFi exposure before surgery based on evidence-based risk modifiers.The propensity-matched sample included 186 patients who received pre-operative biologic therapy (VDZ, n=94; TNFi, n=92). VDZ and TNFi cohorts were similar based on age, gender, IBD type, concomitant immunomodulator exposure, chronic opioid or corticosteroid therapy, Charlson Comorbidity Index and malnutrition. VDZ patients were more likely to undergo an open bowel resection with ostomy. After propensity score matching, there was no significant difference in post-operative SSIs (TNFi 12.0% vs VDZ 14.9%, P=0.56). Multivariable analysis indicated that malnutrition was the sole risk factor for developing SSI (OR 3.1, 95% CI 1.11-8.71) regardless of the type of biologic exposure.In the largest, risk-adjusted cohort analysis to date, perioperative exposure to VDZ therapy was not associated with a significantly higher risk of developing an SSI compared to TNFi therapy.

View details for PubMedID 29876995

Abstract

The aim of this study was to investigate gene expression levels of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling in a pediatric inflammatory bowel disease (IBD) patient population.IBD is a debilitating disease affecting 0.4% of the US population. The incidence of IBD in childhood is rising. Identifying effective targeted therapies that can be used safely in young patients and developing tools for selecting specific candidates for targeted therapies are important goals. Clinical IBD trials now underway target S1PR1, a receptor for the pro-inflammatory sphingolipid S1P. However, circulating and tissue sphingolipid levels and S1P-related gene expression have not been characterized in pediatric IBD.Pediatric IBD patients and controls were recruited in a four-site study. Patients received a clinical score using PUCAI or PCDAI evaluation. Colon biopsies were collected during endoscopy. Gene expression was measured by qRT-PCR. Plasma and gut tissue sphingolipids were measured by LC-MS/MS.Genes of S1P synthesis (SPHK1, SPHK2), degradation (SGPL1), and signaling (S1PR1, S1PR2, and S1PR4) were significantly upregulated in colon biopsies of IBD patients with moderate/severe symptoms compared with controls or patients in remission. Tissue ceramide, dihydroceramide, and ceramide-1-phosphate (C1P) levels were significantly elevated in IBD patients compared with controls.A signature of elevated S1P-related gene expression in colon tissues of pediatric IBD patients correlates with active disease and normalizes in remission. Biopsied gut tissue from symptomatic IBD patients contains high levels of pro-apoptotic and pro-inflammatory sphingolipids. A combined analysis of gut tissue sphingolipid profiles with this S1P-related gene signature may be useful for monitoring response to conventional therapy.

View details for PubMedID 29788359

Abstract

Epidemiologic analyses of acute and chronic pancreatitis (AP and CP) provide insight into causes and strategies for prevention, and affect allocation of resources to its study and treatment. We sought to determine current and accurate incidences of AP and CP, along with the prevalence of CP, in children and adults in the United States.We collected data from the Truven MarketScan Research Databases of commercial inpatient and outpatient insurance claims in the United States from 2007 through 2014 (patients 0-64 years old). We calculated the incidences of AP and CP, and prevalence of CP, based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Children were defined as 18 years or younger and adults as 19 to 64 years old.The incidence of pediatric AP was stable from 2007 through 2014, remaining at 12.3/100,000 persons in 2014. Meanwhile the incidence for adult AP decreased from 123.7/100,000 persons in 2007 to 111.2/100,000 persons in 2014. The incidence of CP decreased over time in children (2.2/100,000 persons in 2007 to 1.9/100,000 persons in 2014) and adults (31.7/100,000 persons in 2007 to 24.7/100,000 persons in 2014). The prevalence of pediatric and adult CP was 5.8/100,000 persons and 91.9/100,000 persons, respectively in 2014. Incidences of AP and CP increased with age; we found little change in incidence during the first decade of life, but linear increases starting in the second decade.We performed a comprehensive epidemiologic analysis of privately insured non-elderly adults and children with AP and CP in the United States. Changes in gallstone formation, smoking, and alcohol consumption, along with advances in pancreatitis management, may be responsible for the stabilization and even decrease in the incidences of AP and CP.

View details for PubMedID 29660323

Abstract

In this prospective cohort study, we examine the feasibility of a protocol to optimize microbiota for fecal microbiota transplantation (FMT). Donor stool metrics generally accepted as markers of gut health were used to select a stool donor based on superior microbial diversity, balanced constitution of Bacteroidetes versus Firmicutes and high concentration of fecal butyrate. Selected donor microbiota was then administered via FMT. A total of 10 patients with median age of 12 years with recurrent Clostridium difficile infection (rCDI) received the intervention. The rate of recurrence-free resolution with 1-2 FMTs was 100% at Week 10. With a single FMT, 80% of patients cleared CDI without recurrence, while 20% of patients required a single re-treatment. No serious adverse events occurred. Microbiota sequencing revealed that recipients' gut microbiota phylogenic diversity increased by 72-hours post-transplantation, with sustainment over 10-week follow-up. This study highlights the feasibility of purposefully selecting the most ideal microbiota for transplantation.

View details for PubMedID 29470297

View details for PubMedID 29509635

Abstract

Severe colitis flare from ulcerative colitis (UC) or Crohn's disease (CD) may be refractory to corticosteroids and antitumour necrosis factor (TNF) agents resulting in high colectomy rates. We aimed to describe the utility of tacrolimus to prevent colectomy during second-line vedolizumab initiation after corticosteroid and anti-TNF treatment failure in paediatric severe colitis.A retrospective cohort analysis was performed between 1 October 2014 and 31 October 2016 at a single tertiary care centre. Inclusion criteria were patients with severe colitis who received tacrolimus before or during vedolizumab induction and previous exposure to anti-TNF therapy with or without corticosteroids. The initiation of tacrolimus was clinician dependent based on an institutional protocol.Twelve patients (10 UC, twoCD; median age 16 years; three female) received at least one dose of vedolizumab 10mg/kg (max of 300mg) due to anti-TNF therapy failure and persistent flare not responsive to corticosteroids. Of the 12 patients, eight (67%) and four (33%) had failed one or two anti-TNF agents, respectively. Tacrolimus was initiated for acute disease severity during hospitalisation (58%) or ongoing flare during outpatient care (42%). 9 (75%) of 12 patients avoided colectomy or inflammatory bowel disease-related surgery at 24 weeks and eight (68%) continued on vedolizumab maintenance with no adverse events out to 80 weeks.We report real-world data on the outcome of tacrolimus around vedolizumab initiation in paediatric UC or CD after corticosteroid and anti-TNF therapy treatment failure. Our pilot experience indicates a potential benefit of concomitant tacrolimus when initiating vedolizumab therapy.

View details for PubMedID 29527316

View details for PubMedCentralID PMC5841492

Abstract

To establish baseline trends in fecal calprotectin, a protein excreted into the stool when there is neutrophilic inflammation in the bowel, in infants at risk for necrotizing enterocolitis (NEC).We performed a prospective observational cohort study in infants with a birth weight of <1500 g without existing bowel disease at a level IV neonatal intensive care unit from October 2015 to September 2016. Stools were collected once daily for 30 days or until 32 weeks postmenstrual age and processed using the Fecal Calprotectin High Range Quantitative Quantum Blue assay.In 64 preterm infants, during the first week after birth, 62% of infants had an initial stool sample with high baseline calprotectin levels (200g/g). In assessment of maternal and neonatal risk factors, maternal etiology for preterm birth (ie, eclamplsia or preeclampsia) was the only significant factor associated with high baseline calprotectin level. Two patients in the cohort developed NEC. Calprotectin levels for the entire cohort fluctuated during the observed period but generally increased in the third and fourth weeks after birth.At-risk infants had highly variable fecal calprotectin levels, with maternal causes for preterm birth associated with higher baseline levels. More longitudinal data in infants with NEC are necessary to determine whether acute rises in fecal calprotectin levels prior to clinical diagnosis can be confirmed as a diagnostic or prognostic biomarker.

View details for PubMedID 29519542

View details for DOI 10.1016/j.acap.2018.01.014

View details for PubMedID 29448049

Abstract

Inadequate infliximab (IFX) drug exposure remains a clinical challenge and leads to high loss of response rates and therapy failure in inflammatory bowel disease (IBD). We aimed to determine the feasibility and pilot effectiveness of a novel, web-based, mobile IFX dosing calculator (mIDC) for therapy optimization.We developed an mIDC leveraging the known clinical variables of C-reative protein (CRP), albumin, patient's weight, disease activity indices, calprotectin, drug trough levels, and antibodies to IFX that significantly affect pharmacokinetics and/or outcomes. A prospective observational cohort study in pediatric and young adult IBD patients receiving maintenance IFX was performed. System-wide practice adoption of mIDC was achieved through a quality improvement (QI) initiative within a hospital-based infusion unit.Forty-nine patients (median age: 16.0 years; 55% female; 65% Crohn's disease) were followed over 9 months. mIDC recommendations for dose optimization were followed by the treating physicians in 198 (89%) out of 222 infusions. Twenty-eight (13%) of 222 mIDC recommendations were to escalate IFX dosing; 15 (54%) of 28 escalation recommendations were declined, and these patients were more likely to already be receiving IFX dose intensification compared with those in whom escalation recommendations were followed (P < 0.05). From mIDC initiation to end of follow-up, mean albumin levels remained unchanged at 3.8 g/dL. Median CRP remained unchanged at 2 g/L. Median calprotectin levels showed a downward trend from 30 to 27 g/g (n = 9, P < 0.05). The percentage of patients undergoing therapeutic drug monitoring in clinical care increased from 34% to 86% with the QI initiative. The target median IFX trough goal of >5 g/mL was achieved with 81% probability throughout the QI initiative, an increase of 12% compared with pre-QI values.The use of a novel mIDC is feasible and potentially effective, facilitating both standardization and individualization of therapy in clinical care. mIDC appears to be a practical IFX dosing tool for point-of-care use, leveraging individual pharmacokinetic considerations.

View details for PubMedID 29361094

Abstract

To assess the correlation between the send-out enzyme-linked immuno sorbent assay (ELISA) and the point-of-care (POC) calprotectin test in pediatric inflammatory bowel disease (IBD) patients.We prospectively collected stool samples in pediatric IBD patients for concomitant send-out ELISA analysis and POC calprotectin testing using the Quantum Blue() (QB) Extended immunoassay. Continuous results between 17 to 1000 g/g were considered for comparison. Agreement between the two tests was measured by a Bland-Altman plot and statistical significance was determined using Pitman's test.Forty-nine stool samples were collected from 31 pediatric IBD patients. The overall means for the rapid and ELISA tests were 580.5 and 522.87 g/g respectively. Among the 49 samples, 18 (37.5%) had POC calprotectin levels of 250 g/g and 31 (62.5%) had levels > 250 g/g. Calprotectin levels 250 g/g show good correlation between the two assays. Less correlation was observed at quantitatively higher calprotectin levels.In pediatric IBD patients, there is better correlation of between ELISA and POC calprotectin measurements at clinically meaningful, low-range levels. Future adoption of POC calprotectin testing in the United States may have utility for guiding clinical decision making in real time.

View details for DOI 10.4292/wjgpt.v8.i2.127

View details for PubMedID 28533922

Abstract

The pharmacokinetics of infliximab are highly variable in children with Crohn's disease (CD), and a one-size-fits-all approach to dosing is inadequate. Model-based drug dosing can help individualize dosing strategies. We evaluated the predictive performance and clinical utility of a published population pharmacokinetic model of infliximab in children with CD.Within a cohort of 34 children with CD who had infliximab trough concentrations measured, the pharmacokinetics of each patient was estimated in NONMEM using a published population pharmacokinetic model. Infliximab concentrations were then predicted based on each patient's dosing history and compared to actual measured concentrations (n=59). In addition, doses 5-10mg/kg and dosing intervals every 4-8 weeks were simulated in each patient to examine dose-trough relationships.Predicted concentrations were within1.0g/ml of actual measured concentrations for 88% of measurements. The median prediction error (i.e. measure of bias) was -0.15g/ml (95%CI: -0.37 to -0.05g/ml) and absolute prediction error (i.e. measure of precision) was 0.26g/ml (95%CI: 0.15 to 0.40g/ml). At standard maintenance dosing of 5mg/kg every 8 weeks, a trough >3g/ml was predicted to be achieved in 32% of patients. To achieve a trough >3g/ml, a dosing interval every 6 weeks was predicted to be required in 29% of patients.A published infliximab population pharmacokinetic model demonstrated accurate predictive performance in a pediatric CD population. Individualized infliximab dosing strategies in children with CD will be critical to consistently achieve trough concentrations associated with optimal outcomes.

View details for DOI 10.1097/MPG.0000000000001620

View details for PubMedID 28471911

Abstract

To determine the impact of the Text Message Educational Automated Compliance Help (TEACH) text message intervention as a pragmatic approach for patient engagement among adolescents with celiac disease (CD) as measured by gluten-free diet (GFD) adherence, patient activation, and quality of life (QOL).Randomized controlled trial with patient recruitment at a pediatric, university-based hospital and through social media; 61 participants ages 12-24 years with CD diagnosed at least 1 year were enrolled. The TEACH intervention cohort received 45 unique text messages over a 3-month study period while the control group received standard of care treatment. Primary outcome measures included objective markers of GFD adherence included serum tissue transglutaminase IgA and deamidated gliadin peptide IgA levels. Secondary patient-reported outcomes collected via online survey included the Celiac Dietary Adherence Test, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Global Short Form measure of QOL, Celiac Symptom Index, and Patient Activation Measure. All measures were assessed at enrollment and after the 3-month study period. Statistical analysis performed using the 2-tailed paired Student t test.Among the TEACH intervention group, there was significant improvement comparing enrollment scores with 3-month follow-up scores in patient activation (Patient Activation Measure score 63.1 vs 72.5, P=.01) and QOL (NIH PROMIS Global Mental Health 50.8 vs 53.3, P=.01 and NIH PROMIS Global Physical Health 50.8 vs 57.7, P=.03). There was no statistically significant difference in patient-reported or objectively measured GFD adherence.TEACH is an effective intervention among patients with CD to improve patient activation and QOL, even among a cohort with GFD adherence at baseline.ClinicalTrials.gov: NCT02458898.

View details for DOI 10.1016/j.jpeds.2017.02.062

View details for PubMedID 28343658

View details for Web of Science ID 000398606900026

View details for Web of Science ID 000393902100005

View details for Web of Science ID 000393902100228

View details for DOI 10.1007/s10620-016-4446-1

View details for PubMedID 28084605

Abstract

Premedications are commonly given to patients with inflammatory bowel disease before intravenous infliximab administration. We aimed to (1) describe practice variability; and (2) determine clinician rationale for premedicating patients with inflammatory bowel disease before infliximab administration.We developed a cross-sectional electronic survey after comprehensive literature review to assess practice variability and clinician rationale for premedication use before infliximab. An optional postsurvey quiz assessed clinicians' understanding of the available literature. The survey was distributed through members-only NASPGHAN and Crohn's and Colitis Foundation of America (CCFA) listservs and American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG) web-based discussion boards.Three hundred seventy-nine unique respondents with a 93.3% survey completion rate comprised 331 (87%) and 45 (12%) pediatric and adult gastroenterologists. Among numerous options for premedications, acetaminophen (66%) and diphenhydramine (64%) were most often given before each infliximab infusion. Only 20% did not routinely use premedications. There was heterogeneity of premedication use between gastroenterologists within the same clinical practice. Of 328 (87%) respondents who completed the knowledge assessment quiz, only 18% identified the association of diphenhydramine use with increased reaction.There is high interpractice and intrapractice variability for premedication use before infliximab administration. Clinician rationale for premedicating patients seems to be driven by individual preference or group practice habit. Improved knowledge of the evidence may assist in decreasing overuse of premedications, particularly diphenhydramine.

View details for DOI 10.1097/MIB.0000000000001002

View details for Web of Science ID 000393897100027

View details for PubMedID 28002131

View details for PubMedCentralID PMC5180444

Abstract

The treatment goal for children suffering from inflammatory bowel disease (IBD) has been evolving with biologic therapies like anti-TNF agents assuming a more central role in treatment of more aggressive and extensive phenotype. Earlier introduction of anti-TNF agents have shown to be more effective and may even alter the natural history of IBD. However, development of anti-drug antibodies (ADA) limits long term usage and leads to dose adjustment in almost half of patients treated with these medications. One of the strategies to minimize the development of ADA has been concomitant use of immunomodulator (IM) medications, resulting in fewer infusion reactions and sustained trough levels, potentially lowering the need for dose adjustments. However, balanced with these benefits of optimized dosing and likely more sustained response, is the concern about increased risk of complications, such as infections and malignancies. The current manuscript reviews the available pediatric literature regarding efficacy, safety and side effect profile of combination (IM and biologics) therapy in pediatric Crohn's disease and ulcerative colitis, with particular emphasis on cost constraints, and recommendations for selection of patients who would benefit most from combination therapy.

View details for PubMedID 29210919

Abstract

In this report, we describe incremental changes, during a 2-year period at a single center with the administration of maintenance infliximab infusions. Given practice-driven changes consisting of 1-hour infusions and omission of premedications, we aimed to investigate if these changes contributed to severe infusion reactions. We reviewed approximately 900 infliximab infusions in a pediatric ambulatory infusion center from January 1, 2014, to December 31, 2015, for severe adverse reactions requiring either rescue epinephrine or a code blue or "rapid response" activation. In 2015, these practice changes resulted in a 51% decrease in total infusion hours (1281 to 630 infusion hours), despite a 9% increase in total number of infusions. No increase in severe adverse events associated with either rapid 1-hour infusion or omission of premedications. Our findings highlight a quality-improvement opportunity to standardize infliximab infusions to streamline care in an ambulatory setting.

View details for PubMedID 28937551

View details for PubMedCentralID PMC5533651

Abstract

Real-world data quantifying the costs of increasing use of biologics in inflammatory bowel disease (IBD) are unknown.To determine the outpatient IBD drug utilization trends, relative market share, and costs in the USA during a 9-year period.The Truven MarketScan Database was analysed for patients with Crohn's disease (CD) and ulcerative colitis (UC) during 2007-2015. National drug codes were used to identify prescription drugs; Healthcare Common Procedure Coding System J-codes were used to capture biologic out-patient infusions. Proportion of drug usage, relative market share and per-member per-year (PMPY) costs were analysed for biologics, immunomodulators, 5-ASAs and corticosteroids.In 415405 patients (188842 CD; 195183 UC; 31380 indeterminate colitis; 54.67% female), utilization trends show a consistent rise in the market share of biologics during the 9-year study period. The proportion of patients using biologics increased from 21.8% to 43.8% for CD and 5.1%-16.2% for UC. This contrasts a small decrease in immunomodulator and 5-ASA use for CD and relative constancy of other classes including corticosteroids-only use as primary IBD medication from 2007 to 2015. The average biologic-taking patient accounted for $25275 PMPY in 2007 and $36051 PMPY in 2015. The average paediatric biologic-taking patient accounted for $23616 PMPY in 2007 and $41109 PMPY in 2015. In all patients, the share of costs for biologics increased from 72.9% in 2007 to 85.7% in 2015 (81.7% in 2007 to 94.9% in 2015 in paediatrics).The vast majority of costs allocated to out-patient IBD medications in the USA is attributed to increasing use of biologic therapies despite the relative minority of biologic-taking patients.

View details for PubMedID 29164650

Abstract

Adolescents with chronic illness face greater risk of psychosocial difficulties, complicating disease management. Despite increased calls to screen for patient-reported outcomes, clinical implementation has lagged. Using quality improvement methods, this study aimed to investigate the feasibility of standardized screening for depression and assessment of global health and to determine recommended behavioral health follow-up, across three pediatric subspecialty clinics.A total of 109 patients aged 12-22years (median= 16.6) who were attending outpatient visits for treatment of diabetes (80% type 1), inflammatory bowel disease, or cystic fibrosis completed the 9-item Patient Health Questionnaire (PHQ-9) depression and Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health measures on electronic tablets. Patients screening positive on the PHQ-9 received same-day behavioral health assessment and regular phone check-ins to facilitate necessary follow-up care.Overall, 89% of 122 identified patients completed screening during a 6-month window. Patients completed measures in a timely manner (within 3minutes) without disruption to clinic flow, and they rated the process as easy, comfortable, and valuable. Depression scores varied across disease type. Patients rated lower global health relative to a previously assessed validation cohort. Depression and global health related significantly to certain medical outcomes. Fifteen percent of patients screened positive on the PHQ-9, of whom 50% confirmed attending behavioral health appointments within 6months of screening.A standardized depression and global health assessment protocol implemented across pediatric subspecialties was feasible and effective. Universal behavioral health screening for adolescents and young adults living with chronic disease is necessary to meet programmatic needs in pediatric subspecialty clinics.

View details for PubMedID 28830798

View details for PubMedID 28816762

View details for PubMedID 28557772

Abstract

In asymptomatic patients with inflammatory bowel disease (IBD), "monitoring" involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review.An electronic search was performed in Medline, Embase, and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist.A total of 1719 articles were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study's cutoff level had a 53% to 83% probability of developing disease relapse within the next 2 to 3 months. Patients with repeated normal FC values had a 67% to 94% probability to remain in remission in the next 2 to 3 months. The ideal FC cutoff for monitoring could not be identified because of the limited number studies meeting inclusion criteria and heterogeneity between selected studies.Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes.

View details for PubMedID 28511198

Abstract

The advent of biosimilars in inflammatory bowel disease (IBD) represents an opportunity for cost-savings and increased patient access to effective disease-modifying therapies. While preliminary data in adult IBD and rheumatology patients suggest comparable effectiveness and pharmacokinetics between original biologics and biosimilars, long-term immunogenicity data are unknown. Without this data, conclusions about interchangeability should not be made for pediatric patients with IBD. Children affected by IBD, in particular, are a vulnerable group if automatic substitution and non-medical switching are allowed based on limited data in adult patients. Robust, long term immunogenicity data of biosimilars are needed in pediatric cohorts before policies allow interchangeability in children.

View details for PubMedID 28319603

Abstract

Tremendous acceleration has been made in understanding the gut microbiota in the past decade and, with it, further understanding of the pathologic role of dysbiosis and the use of fecal microbiota transplantation (FMT) as therapy. FMT has been studied in many disease states including the most common indication of Clostridium difficile infection (CDI), though many questions regarding stool donor selection remain.Though traditionally, one donor has provided stool for one patient, research is underway to explore many donor selection considerations from the use of pooled donor stool to selection of a high diversity donor. It is well-known that dietary intake shapes the gut microbiota and the potential implications of this on FMT donor selection are being explored. Though further high-quality research is needed, optimizing the fecal microbiota inoculum holds great promise.

View details for DOI 10.1007/s11894-017-0548-y

View details for PubMedID 28289858

View details for DOI 10.1111/petr.12836

View details for PubMedID 28191753

Abstract

Patient activation is an important consideration for improved health outcomes in the management of chronic diseases. Limited English proficiency (LEP) among patients and primary care providers has been shown to be a predictor for worse health across disease states. We aimed to determine the baseline patient activation measure (PAM) among Spanish-speaking (SP) and English-speaking (ES) pediatric IBD patients and parents, and to describe the feasibility and efficacy of a novel peer-group education symposium designed to enhance patient activation as measured with the PAM.Two separate half-day educational symposia in either Spanish or English were presented and moderated by 2 native Spanish-speaking physicians. Content for each of the presentations were highly standardized and interactive, designed to address each of the activation domains (self-management, collaboration with a health care provider, maintenance of function and prevention of disease exacerbation, and appropriate access to high-quality care). Descriptive statistics were used to describe changes between pre- and post-symposium PAM trends.11 primarily SP and 21 ES families participated in their respective symposium. Paired pre- and post-PAM scores were available from 24 pediatric IBD patients (8 SP; 16 ES) and 41 parents (15 SP; 26 ES). The mean age for SP and ES patients was 11.6 and 12.0 years, and female gender in 80% and 62%, respectively. Paired pre- and post-PAM scores for all participants (n=65) were analyzed. PAM scores uniformly increased in all 4 groups after the symposia (SP-patients 59.1 to 70.3, P=0.05; SP-parents 69.8 to 75.2, P=0.2; ES-patients 59.9 to 64.0, P=0.08; ES-parents 61.9 to 69.1, P=0.002), although only the ES-parents group had sufficient sample size (n=26) to achieve statistical significance. The overall cohort had an aggregate increase from pre-PAM of 62.9 (SD 14.5) to post-PAM of 69.4 (SD 13.9) (<0.001).We describe a novel peer-group educational symposium presented in Spanish and English languages to increase patient and parent activation in pediatric IBD patients and their care-giving parents. The use of PAM to assess levels of activation appears to be feasible and effective in these groups.

View details for PubMedID 27031374

View details for PubMedID 27789539

Abstract

Research on resident workloads has focused primarily on the quantity of hours worked, rather than the content of those hours or the variability among residents. We hypothesize that there are statistically significant variations in resident workloads and better understanding of workload intensity could improve resident education.The Stanford Children's Health research database was queried for all electronic notes and orders written by pediatric residents from June 2012 to March 2014. The dataset was narrowed to ensure an accurate comparison among residents. A survey was used to determine residents' self-perceived workload intensity. Variability of total notes written and orders entered was analyzed by (2) test and a Monte Carlo simulation. Linear regression was used to analyze the correlation between note-writing and order-entry workload intensity.A total of 20280 notes and 112214 orders were written by 26 pediatric interns during 6 core rotations between June 2012 and June 2013. Both order-entry and note-writing workload intensity showed highly significant (P < .001) variability among residents. "High workload" residents, defined as the top quartile of total workload intensity, wrote 91% more orders and 19% more notes than "low workload" residents in the bottom quartile. Statistically significant correlation was observed between note-writing and order-entry workload intensity (R(2) = 0.22; P = .02). There was no significant correlation between residents' self-perceived workload intensity and their objective workload.Significant variations in workload exist among pediatric residents. This may contribute to heterogeneous educational opportunities, physician wellness, and quality of patient care.

View details for DOI 10.1542/peds.2015-4371

View details for Web of Science ID 000378853100022

View details for PubMedID 27358473

Abstract

Standard infliximab maintenance dosing of 5mg/kg every 8 weeks may be inadequate to consistently achieve sufficient drug exposure to minimize loss of response or treatment failure in pediatric Crohn's disease (CD). We aimed to determine the predicted infliximab trough concentrations in children with CD during maintenance therapy and the percentage of patients achieving target trough concentration >3g/ml.A Monte Carlo simulation analysis was constructed using a published population pharmacokinetic model based on data from 112 children in the REACH trial. We assessed maintenance dosing strategies of 5, 7.5, and 10mg/kg at dosing intervals of every 4, 6, and 8 weeks for children that differed by age, weight, albumin level, and concomitant immunomodulator therapy.Based on the index case of a 10 year old with CD receiving standard infliximab dosing with concomitant immunomodulator therapy, the median (IQR) simulated infliximab trough concentration at week 14 was 1.3 (0.5-2.7) g/ml, and 2.4 (1.0-4.8) g/ml for albumin levels of 3 and 4g/dl, respectively. Among 1000 simulated children in the model, trough concentration >3g/ml at week 14 was achieved 21% and 41% of the time for albumin levels of 3 and 4g/dl, respectively.Standard infliximab maintenance dosing in children with CD is predicted to frequently result in inadequate exposure, especially when albumin levels are low. Optimized dosing strategies for individual patients are needed to achieve sufficient drug exposure during infliximab maintenance therapy.

View details for DOI 10.1097/IWPG.0000000000001123

View details for Web of Science ID 000375334500010

View details for PubMedID 26890885

View details for DOI 10.1097/MPG.0000000000001123

View details for Web of Science ID 000374765900017

Abstract

To investigate the specific carbohydrate diet (SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease (CD).Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple (diet alone, antibiotics or 5-ASA) or SCD with immunomodulators (corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics.The mean age at start of the SCD was 11.8 3.0 years (range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 4.0 mo (range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization (P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization.Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

View details for DOI 10.3748/wjg.v22.i6.2111

View details for PubMedID 26877615

View details for PubMedCentralID PMC4726683

Abstract

To investigate the specific carbohydrate diet (SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease (CD).Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple (diet alone, antibiotics or 5-ASA) or SCD with immunomodulators (corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics.The mean age at start of the SCD was 11.8 3.0 years (range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 4.0 mo (range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization (P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization.Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

View details for DOI 10.3748/wjg.v22.i6.2111

View details for Web of Science ID 000368559400016

View details for PubMedCentralID PMC4726683

Abstract

The cost of medical care for Crohn's disease (CD) and comorbidities in the era of biologics is unclear. We examined insurance claims data from US health plans to understand this relationship.Longitudinal CD patient data and reimbursement information from 11 health plans engaged with Accordant Health Services between 2011 and 2013 were analyzed. The analysis considered data for all CD patients and for the patient subgroup 20 years and >20 years of age. Descriptive statistics measured the mean health-plan paid costs per patient, the relative cost contribution of anti-tumor necrosis factor (TNF) agents, and health care costs for 31 specific comorbid conditions among CD patients.Overall, there were 5,090 CD patients (57% women) of which 587 CD patients were 20 years of age. The mean health-plan paid cost per member per year was $18,637 (s.d. $32,023) for all CD patients, $22,796 (s.d. $ 41,905) for CD patients 20 years, and $18,095 (s.d. $30,065) for patients >20 years of age. Twenty-eight percent of CD patients accounted for 80% of total costs. No differences were found in costs based on gender. Increased health-plan paid costs were significantly correlated with the number of comorbid conditions across all ages. Pharmacy utilization costs account for nearly one-half (45.5%) of the total CD-attributable costs, exceeding inpatient care costs. Anti-TNF agents alone comprised nearly one-third (29.5%) of total costs. Aside from anti-TNF costs, other major categories of expense were as follows: inpatient 23.1%, outpatient hospital setting 15.7%, and MD office 8.2%.Total health-care costs in CD exceed previous estimates, with the majority of costs being allocated to a relatively small subgroup of patients. Pharmacy utilization costs, owing to anti-TNF use, result in increasing total health-care costs and currently exceed costs for inpatient care. Pragmatic strategies to encourage gastroenterologists in the best clinical practice of optimizing anti-TNF use-in particular for younger age patients and those with multiple comorbidities-are necessary to reduce avoidable pharmacy utilization and inpatient care costs.Am J Gastroenterol advance online publication, 21 July 2015; doi:10.1038/ajg.2015.207.

View details for DOI 10.1038/ajg.2015.207

View details for Web of Science ID 000374258500006

View details for PubMedID 26195179

Abstract

The relationship between limited English proficiency (LEP) and worse pediatric health outcomes is well documented.To determine the relationship between LEP status and pediatric hospital readmissions.We performed a retrospective cohort analysis of children 18 years old admitted to a tertiary children's hospital from 2008 to 2014. The main exposure was LEP status. Independent variables included sex, age, race/ethnicity, insurance, median household income, surgical/medical status, severity of illness (SOI), the presence of a complex chronic condition, and length of stay. Primary outcome measures were 7- and 30-day readmission.From 67473 encounters, 7- and 30-day readmission rates were 3.9% and 8.2%, respectively. LEP patients were more likely to be younger, poorer, and Hispanic; have lower SOI; and government-subsidized insurance. Adjusted odds for 7- or 30-day readmission for LEP versus English-proficient (EP) patients were 1.00 (P = .99) and 0.97 (P = .60), respectively. Hispanic ethnicity (adjusted odds ratio [aOR]: 1.26 [P = .002] and 1.14 [P = .02]), greater SOI (aOR: 1.04 [P < .001] and 1.05 [P < .001]), and the presence of a complex chronic condition (aOR: 2.31 [P < .001] and 3.03 [P < .001]) were associated with increased odds of 7- and 30-day readmission, respectively. White LEP patients had increased odds of 7- and 30-day readmission compared with white EP patients (aOR: 1.46 [P = .006] and 1.32 [P = .007]) and the poorest LEP patients had increased odds of 7- and 30-day readmission compared with the poorest EP patients (aOR: 1.77 [P = .04] and 2.00 [P < .001]).This is the first large study evaluating the relationship between LEP and pediatric hospital readmission. There was no increased risk of readmission in LEP patients compared with EP patients.

View details for PubMedID 27923838

View details for PubMedID 27465505

View details for PubMedCentralID PMC5018915

View details for PubMedID 27504814

Abstract

There are no head-to-head randomised controlled trials (RCTs) comparing the effectiveness of biologics in ulcerative colitis (UC). We aimed to assess the cost-effectiveness of adalimumab, infliximab and vedolizumab as first-line agents to induce clinical remission and mucosal healing (MH) in UC.We constructed a decision tree based on a payer's perspective in the USA to estimate the first year costs of adalimumab, infliximab or vedolizumab to achieve clinical remission and MH in patients with moderate-to-severe UC. Transition probabilities were derived from ACT, ULTRA and GEMINI RCT data. Costs were derived from Medicare reimbursement rates and wholesale drug prices.Assuming a biological-nave cohort, infliximab 5mg/kg every 8weeks was more cost-effective ($99171 per MH achieved) than adalimumab 40mg every other week ($316378 per MH achieved) and vedolizumab every 8weeks ($301969 per MH achieved) at 1year. Non-drug administration cost of infliximab exceeding $1974 per infusion would make adalimumab more cost-effective. First-line UC therapy with vedolizumab would be cost-effective if the drug acquisition price was <$2537 for each 300mg administration during the 1-year time horizon.If non-drug costs of infliximab administration are not excessive (<$2000), infliximab is the most cost-effective first-line biologic for moderate-to-severe UC. Exceeding this threshold infusion-related cost would make adalimumab the more cost-effective therapy. Considering its drug costs in the USA, vedolizumab appears to be appropriately used as a second-line biologic after antitumour necrosis factor failure.

View details for DOI 10.1136/bmjgast-2016-000093

View details for PubMedID 27195130

View details for DOI 10.1089/acu.2015.1144

View details for Web of Science ID 000217806700012

View details for Web of Science ID 000370860202722

View details for Web of Science ID 000363715903441

View details for Web of Science ID 000363715905002

Abstract

Pediatric inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), can result in significant morbidity requiring frequent health care utilization. Although it is known that the overall financial impact of pediatric IBD is significant, the direct out-of-pocket (OOP) cost burden on the parents of children with IBD has not been explored. We hypothesized that affected children with a more relapsing disease course and families in lower income strata, ineligible for need-based assistance programs, disparately absorb ongoing financial stress.We completed a cross-sectional analysis among parents of children with IBD residing in California using an online HIPAA-secure Qualtrics survey. Multicenter recruitment occurred between December 4, 2013 and September 18, 2014 at the point-of-care from site investigators, informational flyers distributed at regional CCFA conferences, and social media campaigns equally targeting Northern, Central, and Southern California. IBD-, patient-, and family-specific information were collected from the parents of pediatric patients with IBD patients younger than 18 years of age at time of study, carry a confirmed diagnosis of CD or UC, reside in and receive pediatric gastroenterology care in California, and do not have other chronic diseases requiring ongoing medical care.We collected 150 unique surveys from parents of children with IBD (67 CD; 83 UC). The median patient age was 14 years for both CD and UC, with an overall 3.7 years (SD 2.8 yr) difference between survey completion and time of IBD diagnosis. Annually, 63.6%, 28.6%, and 5.3% of families had an OOP cost burden >$500, >$1000, and >5000, respectively. Approximately one-third (36.0%) of patients had emergency department (ED) visits over the past year, with 59.2% of these patients spending >$500 on emergency department copays, including 11.1% who spent >$5000. Although 43.3% contributed <$500 on procedure and test costs, 20.0% spent >$2000 in the past year. Families with household income between $50,000 and $100,000 had a statistically significant probability (80.6%) of higher annual OOP costs than families with lower income <$50,000 (20.0%; P < 0.0001) or higher income >$100,000 (64.6%; P < 0.05). Multivariate analysis revealed that clinical variables associated with uncontrolled IBD states correlated to higher OOP cost burden. Annual OOP costs were more likely to be >$500 among patients who had increased spending on procedures and tests (odds ratio [OR], 5.63; 95% confidence interval [CI], 2.73-11.63), prednisone course required over the past year (OR, 3.19; 95% CI, 1.02-9.92), at least 1 emergency department visit for IBD symptoms (OR, 2.84; 95% CI, 1.33-6.06), at least 4 or more outpatient primary medical doctor visits for IBD symptoms (OR, 2.82; 95% CI, 1.40-5.68), and history of 4 or more lifetime hospitalizations for acute IBD care (OR, 2.60; 95% CI, 1.13-5.96).Previously undocumented, a high proportion of pediatric IBD families incur substantial OOP cost burden. Patients who are frequently in relapsing and uncontrolled IBD states require more acute care services and sustain higher OOP cost burden. Lower middle income parents of children with IBD ineligible for need-based assistance may be particularly at risk for financial stress from OOP costs related to ongoing medical care.

View details for DOI 10.1097/MIB.0000000000000374

View details for Web of Science ID 000355315800020

View details for PubMedID 25839776

Abstract

Goal. We assessed the effectiveness of bioactive polyphenols contained in solution (LX) to restore normal bowel function in pediatric patients with acute diarrhea. Background. While providing oral rehydration solution (ORS) is standard treatment for diarrhea in developing countries, plant-derived products have been shown to positively affect intestinal function. If a supplement to ORS resolves diarrhea more rapidly than ORS alone, it is an improvement to current care. Study. In a randomized, double-blind, placebo-controlled cross-over study, 61 pediatric patients with uncontrolled diarrhea were randomized to receive either ORS + LX on day 1 and then ORS + water on day 2 (study arm) or ORS + water on day 1 and then ORS + LX on day 2 (control arm). Time to resolution and number of bowel movements were recorded. Results. On day 1, the mean time to diarrhea resolution was 3.1 h (study arm) versus 9.2 h (control arm) (p = 0.002). In the study arm, 60% of patients had normal stool at their first bowel movement after consumption of the phenolic redoxigen solution (LX). On day 2, patients in the study arm continued to have normal stool while patients in the control arm achieved normal stool within 24 h after consuming the test solution. Patients in the control arm experienced a reduction in the mean number of bowel movements from day 1 to day 2 after consuming the test solution (p = 0.0001). No adverse events were observed. Conclusions. Significant decreases in bowel movement frequency and rapid normalization of stool consistency were observed with consumption of this novel solution.

View details for DOI 10.7717/peerj.969

View details for Web of Science ID 000355125300004

View details for PubMedID 26038724

View details for PubMedCentralID PMC4451028

Abstract

To analyze the prevalence, predictors, and evolution of increased liver enzymes in a large sample of adolescents hospitalized with anorexia nervosa (AN).Electronic medical records of all subjects 10-22years of age with AN, first admitted to a tertiary children's hospital from January 2007 to December 2012, were reviewed retrospectively. Demographic factors, anthropometric factors, initial prescribed calories, and alanine aminotransferase levels were recorded. Multivariate analysis was performed to assess the effect of sex, degree of malnutrition, and initial calories prescribed on having alanine aminotransferase 40 IU/L.A total of 356 subjects met eligibility criteria (age 16.12.4; 89.0% female; admission body mass index [BMI] 15.91.9; admission percentage median BMI 78.28.5), with elevated liver enzymes present in 37.0% on admission and in 41.1% at any point during the hospitalization. Lower percentage median BMI (aOR 0.96; 95% CI 0.93-0.98) and male sex (aOR 0.45; 95% CI 0.22-0.94) were significantly associated with odds of elevated liver enzymes on admission. Higher initial prescribed calories were associated with odds of elevated liver enzymes after admission (aOR 1.81; 95% CI 1.04-3.18).In this study of AN and elevated liver enzymes, the degree of malnutrition and male sex predicted elevated liver enzymes on admission but initial prescribed calories also may be associated with elevated liver enzymes after admission in a small proportion of patients. Future research should better characterize the evolution of elevated liver enzymes in patients hospitalized with AN undergoing refeeding.

View details for DOI 10.1016/j.jpeds.2014.10.048

View details for Web of Science ID 000348496200047

View details for PubMedID 25477162

View details for DOI 10.1016/j.jadohealth.2014.10.178

View details for Web of Science ID 000375069900174

Abstract

Over 9.6 million ED visits occur annually for abdominal pain in the US, but little is known about the medical outcomes of these patients based on demographics. We aimed to identify disparities in outcomes among children presenting to the ED with abdominal pain linked to race and SES.Data from 4.2 million pediatric encounters of abdominal pain were analyzed from 43 tertiary US children's hospitals, including 2.0 million encounters in the emergency department during 2004-2011. Abdominal pain was categorized as functional or organic abdominal pain. Appendicitis (with and without perforation) was used as a surrogate for abdominal pain requiring emergent care. Multivariate analysis estimated likelihood of hospitalizations, radiologic imaging, ICU admissions, appendicitis, appendicitis with perforation, and time to surgery and hospital discharge.Black and low income children had increased odds of perforated appendicitis (aOR, 1.42, 95% CI, 1.32- 1.53; aOR, 1.20, 95% CI 1.14 - 1.25). Blacks had increased odds of an ICU admission (aOR, 1.92, 95% CI 1.53 - 2.42) and longer lengths of stay (aHR, 0.91, 95% CI 0.86 - 0.96) than Whites. Minorities and low income also had lower rates of imaging for their appendicitis, including CT scans. The combined effect of race and income on perforated appendicitis, hospitalization, and time to surgery was greater than either separately.Based on race and SES, disparity of health outcomes exists in the acute ED setting among children presenting with abdominal pain, with differences in appendicitis with perforation, length of stay, and time until surgery.

View details for DOI 10.1371/journal.pone.0132758

View details for PubMedID 26267816

Abstract

To analyze the prevalence, predictors, and evolution of increased liver enzymes in a large sample of adolescents hospitalized with anorexia nervosa (AN).Electronic medical records of all subjects 10-22years of age with AN, first admitted to a tertiary children's hospital from January 2007 to December 2012, were reviewed retrospectively. Demographic factors, anthropometric factors, initial prescribed calories, and alanine aminotransferase levels were recorded. Multivariate analysis was performed to assess the effect of sex, degree of malnutrition, and initial calories prescribed on having alanine aminotransferase 40 IU/L.A total of 356 subjects met eligibility criteria (age 16.12.4; 89.0% female; admission body mass index [BMI] 15.91.9; admission percentage median BMI 78.28.5), with elevated liver enzymes present in 37.0% on admission and in 41.1% at any point during the hospitalization. Lower percentage median BMI (aOR 0.96; 95% CI 0.93-0.98) and male sex (aOR 0.45; 95% CI 0.22-0.94) were significantly associated with odds of elevated liver enzymes on admission. Higher initial prescribed calories were associated with odds of elevated liver enzymes after admission (aOR 1.81; 95% CI 1.04-3.18).In this study of AN and elevated liver enzymes, the degree of malnutrition and male sex predicted elevated liver enzymes on admission but initial prescribed calories also may be associated with elevated liver enzymes after admission in a small proportion of patients. Future research should better characterize the evolution of elevated liver enzymes in patients hospitalized with AN undergoing refeeding.

View details for DOI 10.1016/j.jpeds.2014.10.048

View details for PubMedID 25477162

View details for DOI 10.1007/s10620-014-3094-6

View details for Web of Science ID 000340051200075

View details for PubMedID 24633574

Abstract

BACKGROUND: Clinic no shows (NS) create a lost opportunity for provider-patient interaction and impose a financial burden to the healthcare system and on society. We aimed to: (1) to determine the clinical and demographic factors associated with increased NS rates at a children's hospital's subsubspecialty clinics and (2) to estimate the direct institutional financial costs associated with NS events. METHODS: A comprehensive database was generated from all clinic encounters for 15 subspecialty outpatient clinics (five surgical and 10 medical) between September 12, 2005 and December 30, 2010. Multivariate logistic regressions were performed to identify the variables associated with NS events. Direct costs of NS events were estimated using annual revenue for each clinic. RESULTS: A total of 284,275 encounters and 17,024 NS events were available for analysis. Public insurance coverage (Medicaid and Title V), compared to private insurance or self-pay status, was associated with an increased likelihood NS (OR 2.19, 95% CI 2.10-2.28, p < 0.0005 for Medicaid; OR 1.56, 95% CI 1.50-1.62, p < 0.0005 for Title V). Compared to patients 21-30 years of age, patients <12 years (OR 2.08, 95% CI 1.77-2.45, p < 0.0005) had increased likelihood of NS. Scheduled visits with medical subspecialists were more likely than surgical subspecialty visits to result in a NS (OR 1.69, 95% CI 1.63-1.75, p < 0.0005). The predicted annualized lost revenue associated with NS visits was estimated at $730,000 from the 15 clinics analyzed, approximately $210 per NS event. CONCLUSION: Pediatric subspecialty NS events are common, costly, and potentially preventable.

View details for Web of Science ID 000348450800003

View details for PubMedID 23551280

Abstract

Utilization trends and health effects of infliximab and adalimumab in inflammatory bowel disease (IBD) are incompletely understood. We aimed to describe utilization trends of these 2 anti-tumor necrosis factor (TNF) agents, determine the correlation between utilization with rates of hospitalization and surgery and describe differences in use between adults and children.Longitudinal data were analyzed for drug utilization, hospitalization, and abdominal surgery. Descriptive statistics were used to show trends, and utilization quotients were compared for standardization. Multivariate logistic regression analysis assessed the association between drug use and rates of hospitalization and surgery.Four hundred thirty-eight pediatric and 2514 adult patients with IBD generated a total of 51,882 inpatient and outpatient encounters, representing 1185 Crohn's disease, 1531 ulcerative colitis, and 236 indeterminate colitis patients. From 2007 through 2012, utilization quotients declined for hospitalization but remained unchanged for surgery; adalimumab saw a 3-fold increase, despite continued dominance of infliximab. Median band and mean fitted plots showed downward hospitalization trends from 2006 to 2012. Utilization of infliximab peaked in 2008, Q4 with gradual decline to 2012, Q2; and adalimumab showed moderate increased utilization since 2007, Q1. Use of infliximab (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.70-0.83) and adalimumab (OR, 0.79; 95% CI, 0.72-0.87) was associated with decreased hospitalization risk but not associated with reduced abdominal surgery risk. Children had increased hospitalization (OR, 2.68; 95% CI, 2.49-2.88) but decreased risk for abdominal surgery (OR, 0.57; 95% CI, 0.46-0.70).Current infliximab use remains substantially greater than adalimumab use, despite recent increased use of adalimumab. Although trends for hospitalization for IBD are decreasing, it is not reflected in abdominal surgery rates in a tertiary IBD referral center.

View details for DOI 10.1097/MIB.0000000000000061

View details for PubMedID 24846718

Abstract

The level of fecal calprotectin (FC) can predict the onset of inflammatory bowel disease (IBD) with high accuracy and precision. We evaluated the cost-effectiveness of using measurements of FC to identify adults and children who require endoscopic confirmation of IBD.We constructed a decision analytic tree to compare the cost-effectiveness of measuring FC before endoscopy examination with that of direct endoscopic evaluation alone. A second decision analytic tree was constructed to evaluate the cost-effectiveness of FC cutoff levels of 100 g/g vs 50 g/g (typically used to screen for intestinal inflammation). The primary outcome measure was the incremental cost required to avoid 1 false-negative result by using FC level to diagnose new-onset IBD.In adults, FC screening saved $417/patient but delayed diagnosis for 2.2/32 patients with IBD among 100 screened patients. In children, FC screening saved $300/patient but delayed diagnosis for 4.8/61 patients with IBD among 100 screened patients. If endoscopic biopsy analysis remained the standard for diagnosis, direct endoscopic evaluation would cost an additional $18,955 in adults and $6250 in children to avoid 1 false-negative result from FC screening. Sensitivity analyses showed that cost-effectiveness of FC screening varied with the sensitivity of the test and the pre-test probability of IBD in adults and children. Pre-test probabilities for IBD of 75% in adults and 65% in children made FC screening cost-effective, but it was cost-ineffective if the probabilities were 85% and 78% in adults and children, respectively. Compared with the FC cutoff level of 100 g/g, the cutoff level of 50 g/g cost an additional $55 and $43 for adults and children, respectively, but it yielded 2.4 and 6.1 additional accurate diagnoses of IBD per 100 screened adults and children, respectively.Screening adults and children to measure fecal levels of calprotectin is effective and cost-effective in identifying those with IBD on a per-case basis when the pre-test probability is 75% for adults and 65% for children. The utility of the test is greater for adults than children. Increasing the FC cutoff level to 50 g/g increases diagnostic accuracy without substantially increasing total cost.

View details for DOI 10.1016/j.cgh.2013.06.028

View details for Web of Science ID 000329754900016

View details for PubMedID 23883663

View details for PubMedCentralID PMC3865226

Abstract

Patients with celiac disease (CD) are increasingly interconnected through social media, exchanging patient experiences and health-tracking information between individuals through various web-based platforms. Social media represents potentially unique communication interface between gastroenterologists and active social media users - especially young adults and adolescents with celiac disease-regarding adherence to the strict gluten-free diet, gastrointestinal symptoms, and meaningful discussion about disease management. Yet, various social media platforms may be underutilized for research purposes to collect patient-reported outcomes data. In this commentary, we summarize the scientific rationale and potential for future growth of social media in patient-reported outcomes research, focusing on college freshmen with celiac disease as a case study and provide overview of the methodological approach. Finally, we discuss how social media may impact patient care in the future through increasing mobile technology use.

View details for PubMedID 25392743

Abstract

: A health care system is needed where care is based on the best available evidence and is delivered reliably, efficiently, and less expensively (best care at lower cost). In gastroenterology, anti-tumor necrosis factor agents represent the most effective medical therapeutic option for patients with moderate-to-severe inflammatory bowel disease (IBD), but are very expensive and account for nearly a quarter of the cost of IBD care, representing a major area of present and future impact in direct health care costs. The ImproveCareNow Network, consisting of over 55 pediatric IBD centers, seeks ways to improve the value of care in IBD, curtailing unnecessary costs and promoting better health outcomes through systematic and incremental quality improvement initiatives. This report summarizes the key evidence to facilitate the cost-effective use of anti-tumor necrosis factor agents for patients with IBD. Our review outlines the scientific rationale for initiating cost-reducing measures in anti-tumor necrosis factor use and focuses on 3 implementable strategies and 4 exploratory considerations through practical clinical guidelines, as supported by existing evidence. Implementable strategies can be readily integrated into today's daily practice, whereas exploratory considerations can guide research to support future implementation.

View details for PubMedID 24451222

Abstract

Background. Socioeconomic factors and insurance status have not been correlated with differential use of healthcare services in inflammatory bowel disease (IBD). Aim. To describe IBD-related expenditures based on insurance and household income with the use of inpatient, outpatient, emergency, and office-based services, and prescribed medications in the United States (US). Methods. We evaluated the Medical Expenditure Panel Survey from 1996 to 2011 of individuals with Crohn's disease (CD) or ulcerative colitis (UC). Nationally weighted means, proportions, and multivariate regression models examined the relationships between income and insurance status with expenditures. Results. Annual per capita mean expenditures for CD, UC, and all IBD were $10,364 (N = 238), $7,827 (N = 95), and $9,528, respectively, significantly higher than non-IBD ($4,314, N = 276, 372, p < 0.05). Publicly insured patients incurred the highest costs ($18,067) over privately insured ($8,014, p < 0.05) or uninsured patients ($5,129, p < 0.05). Among all IBD patients, inpatient care composed the highest proportion of costs ($3,392, p < 0.05). Inpatient costs were disproportionately higher for publicly insured patients. Public insurance had higher odds of total costs than private (OR 2.13, CI [1.08-4.19]) or no insurance (OR 4.94, CI [1.26-19.47]), with increased odds for inpatient and emergency care. Private insurance had higher costs associated with outpatient care, office-based care, and prescribed medicines. Low-income patients had lower costs associated with outpatient (OR 0.38, CI [0.15-0.95]) and office-based care (OR 0.21, CI [0.07-0.62]). Conclusions. In the US, high inpatient utilization among publicly insured patients is a previously unrecognized driver of high IBD costs. Bridging this health services gap between SES strata for acute care services may curtail direct IBD-related costs.

View details for DOI 10.7717/peerj.587

View details for PubMedID 25279267

View details for PubMedCentralID PMC4179397

Abstract

We sought to characterize emergency department (ED) encounters for pediatric inflammatory bowel disease (IBD) to identify areas for prevention.Retrospective chart review of 5 consecutive ED encounters at 7 centers.Of 35 unique encounters by 32 subjects, 3 main factors contributed to ED utilization: disease severity or course, day or time of care, and physician instruction. Of the ED encounters, approximately one-fifth were judged medically unnecessary, and one-half avoidable in a more optimal health care system.ED visits by pediatric IBD patients may be reduced in a more optimal health care system.

View details for PubMedID 24918980

Abstract

Allergic rhinitis is diagnosed by clinical parameters with no widely accepted screening test. Measurement of total serum immunoglobulin E (IgE) has limited use in the general population due to a low negative predictive value. The value of total IgE level in select populations undergoing in vitro allergy testing remains unknown. The aim of this study is to determine the utility of total serum IgE in the in vitro diagnosis of allergic rhinitis.A retrospective chart review of patients undergoing testing for allergic rhinitis was performed. Clinical parameters, total IgE level, and enzyme-linked immunosorbent assay (ELISA) for serum-specific IgE levels were analyzed with multivariate logistic regression. The positive and negative predictive values and a receiver operating characteristic (ROC) curve were used to assess the utility of total IgE in predicting serum-specific IgE test results.Records from 1073 patients were reviewed. ROC curve for total IgE >150 IU/mL ( 0.88) indicates good discrimination in identifying patients with sensitization by in vitro testing, whereas low total IgE level had strong negative predictive value (0.87, IgE <10) in identifying negative specific IgE testing. Multivariate logistic regression showed that differences in covariables did not significantly change the odds of a positive in vitro allergy test panel.Serum total IgE level is useful in the in vitro diagnosis of allergic rhinitis. In vitro testing for specific IgE may be unnecessary in patients with low serum total IgE, whereas high total IgE level suggests that in vitro testing would confirm specific sensitizations in patients with allergic rhinitis.

View details for DOI 10.1002/alr.21240

View details for Web of Science ID 000329152400011

View details for PubMedID 24227797

View details for Web of Science ID 000321439600101

Abstract

Patients with asymptomatic or poorly managed celiac disease can experience bone loss, placing them at risk for hip and vertebral fractures. We analyzed the cost-effectiveness of universal serologic screening (USS) vs symptomatic at-risk screening (SAS) strategies for celiac disease because of the risk of nontraumatic hip and vertebral fractures if untreated or undiagnosed.We developed a lifetime Markov model of the screening strategies, each with male or female cohorts of 1000 patients who were 12 years old when screening began. We screened serum samples for levels of immunoglobulin A, compared with tissue transglutaminase and total immunoglobulin A, and findings were confirmed by mucosal biopsy. Transition probabilities and quality of life estimates were obtained from the literature. We used generalizable cost estimates and Medicare reimbursement rates and ran deterministic and probabilistic sensitivity analyses.For men, the average lifetime costs were $8532 and $8472 for USS and SAS strategies, respectively, corresponding to average quality-adjusted life year gains of 25.511 and 25.515. Similarly for women, costs were $11,383 and $11,328 for USS and SAS strategies, respectively, corresponding to quality-adjusted life year gains of 25.74 and 25.75. Compared with the current standard of care (SAS), USS produced higher average lifetime costs and lower quality of life for each sex. Deterministic and probabilistic sensitivity analyses showed that the model was robust to realistic changes in all the variables, making USS cost-ineffective on the basis of these outcomes.USS and SAS are similar in lifetime costs and quality of life, although the current SAS strategy was overall more cost-effective in preventing bone loss and fractures among patients with undiagnosed or subclinical disease. On the basis of best available supportive evidence, it is more cost-effective to maintain the standard celiac screening practices, although future robust population-based evidence in other health outcomes could be leveraged to reevaluate current screening guidelines.

View details for DOI 10.1016/j.cgh.2012.12.037

View details for PubMedID 23357490

Abstract

: Infliximab is the most widely used biological agent for Crohn's disease (CD) and ulcerative colitis (UC) but requires outpatient infusion units because of its intravenous administration requirement. The aim of this study was (1) to determine the average non-drug costs associated with each outpatient use of infliximab for pediatric inflammatory bowel disease and (2) to determine the proportion of non-drug costs associated with each outpatient infliximab use relative to the total cost of each encounter.: Hospital administrative and pharmacy databases were queried for all short stay unit encounters at Lucile Packard Children's Hospital at Stanford University linked to infliximab infusions for inflammatory bowel disease between January 1, 2006, and December 31, 2011. Infliximab drug and non-drug costs associated with CD and UC were compared.: A total of 771 unique encounters were generated for 76 pediatric patients (53 CD, 23 UC). For direct costs related to infliximab infusions for either CD or UC patients, more than 77% of the total health care costs per encounter were related to personnel (e.g., nursing), facility operations, and laboratory costs. Only 23% of the total costs were related to the actual infliximab drug costs. Based on an 80/20 payor mix of managed care versus government-subsidized insurance payers, 24.5% of the total reimbursements were applied to non-drug costs in CD and 20.9% in UC.: Non-drug costs represent a substantial proportion of the total cost of outpatient infliximab-related actual costs in inflammatory bowel disease. Personnel costs represent the largest segment of the non-drug costs. The actual drug costs of infliximab represent a small proportion of the total costs.

View details for DOI 10.1097/MIB.0b013e318281f4f1

View details for PubMedID 23567783

View details for PubMedCentralID PMC3665698

Abstract

To determine whether children in rural areas have worse health than children in urban areas after liver transplantation (LT).We used urban influence codes published by the US Department of Agriculture to categorize 3307 pediatric patients undergoing LT in the United Network of Organ Sharing database between 2004 and 2009 as urban or rural. Allograft rejection, patient death, and graft failure were used as primary outcome measures of post-LT health. Pediatric end-stage liver disease/model of end-stage liver disease scores >20 was used to measure worse pre-LT health.In a multivariate analysis, we found greater rates of allograft rejection within 6 months of LT (OR 1.27; 95% CI 1.05-1.53) and a lower occurrence of posttransplantation lymphoproliferative disorder (OR 0.64; 95% CI 0.41-0.99) in patients in rural areas. The difference in allograft rejection was eliminated at 1 year of LT (OR 1.18; 95% CI 0.98-1.42). Rural location did not impact other outcome measures.We conclude that rural location makes a negative impact on patient health within the first 6 months of LT by increasing the risk for allograft rejection, although patients in rural areas may have lower rates of developing posttransplantation lymphoproliferative disorder. Long-term adverse health effects were not seen.

View details for DOI 10.1016/j.jpeds.2012.07.015

View details for Web of Science ID 000313579900021

View details for PubMedID 22914224

Abstract

Pediatric liver transplant (OLT) patients are at risk of posttransplant lymphoproliferative disease (PTLD) from Epstein-Barr virus (EBV). This study examined the impact of induction and immunosuppression on EBV viremia.A retrospective chart review was performed on 197 pediatric patients and induction regimen, immunosuppression levels, and EBV viremia were documented for 1 year post-OLT. Logistic regression models determined associations between induction, immunosuppression, and EBV.Fifty six percent of patients developed EBV viremia. Incidence of EBV viremia was 73% with antithymocyte globulin (ATG), 63% with daclizumab, and 39% for neither, though the trend was not significant [ATG: odds ratio (OR) 0.19; 95% confidence interval (CI) 0.024-1.58; P = .125; daclizumab OR; 1.07; 95% CI 0.270-4.23; P = .925]. Tacrolimus immunosuppression levels were supratherapeutic 28.7% of the time; however, only supratherapeutic tacrolimus levels between 0 and 2 weeks increased EBV viremia at 2 to 4 weeks post-OLT (OR 1.80; 95% CI 1.10-2.94; P = .02). Three patients developed PTLD.The use of ATG and daclizumab induction likely does not play a role in the development of EBV viremia. Supratherapeutic tacrolimus levels 0 to 2 weeks post-OLT impact the development of EBV viremia at 2 to 4 weeks. The incidence of PTLD was low, suggesting better EBV and immunosuppression monitoring plays an important role in reducing PTLD.

View details for DOI 10.1016/j.transproceed.2012.04.035

View details for Web of Science ID 000315007200060

View details for PubMedID 23267800

Abstract

Inflammatory bowel diseases are costly chronic gastrointestinal diseases. We aimed to determine whether immediate colectomy with ileal pouch-anal anastamosis (IPAA) after diagnosis of severe ulcerative colitis (UC) was cost-effective compared to the standard medical therapy.We created a Markov model simulating 2 cohorts of 21-year-old patients with severe UC, following them until 100 years of age or death, comparing early colectomy with IPAA strategy to the standard medical therapy strategy. Deterministic and probabilistic analyses were performed.Standard medical care accrued a discounted lifetime cost of $236,370 per patient. In contrast, early colectomy with IPAA accrued a discounted lifetime cost of $147,763 per patient. Lifetime quality-adjusted life-years gained (QALY-gained) for standard medical therapy was 20.78, while QALY-gained for early colectomy with IPAA was 20.72. The resulting incremental cost-effectiveness ratio (costs/QALY) was approximately $1.5 million per QALY-gained. Results were robust to one-way sensitivity analyses for all variables in the model. Quality-of-life after colectomy with IPAA was the most sensitive variable impacting cost-effectiveness. A low utility value of less than 0.7 after colectomy with IPAA was necessary for the colectomy with IPAA strategy to be cost-ineffective.Under the appropriate clinical settings, early colectomy with IPAA after diagnosis of severe UC reduces health care expenditures and provides comparable quality of life compared to exhaustive standard medical therapy.

View details for DOI 10.1097/SLA.0b013e3182445321

View details for Web of Science ID 000306083300020

View details for PubMedID 22270693

View details for DOI 10.1097/MPG.0b013e318250a74d

View details for Web of Science ID 000304115900003

View details for PubMedID 22367340

View details for DOI 10.1007/s10620-011-1808-6

View details for Web of Science ID 000298968500005

View details for PubMedID 21735080

View details for DOI 10.1097/MPG.0b013e3182354d50

View details for Web of Science ID 000298550800002

View details for PubMedID 22197853

Abstract

Inflammatory bowel diseases (IBDs) are costly chronic gastrointestinal diseases, with pediatric IBD representing increased costs per patient compared to adult disease. Health care expenditures for ulcerative colitis (UC) are >$2 billion annually. It is not clear whether the addition of VSL#3 to standard medical therapy in UC induction and maintenance of remission is a cost-effective strategy.We performed a systematic review of the literature and created a Markov model simulating a cohort of 10-year-old patients with severe UC, studying them until 100 years of age or death. We compared 2 strategies: standard medical therapy versus medical therapy + VSL#3. For both strategies, we assumed that patients progressed through escalating therapies--mesalamine, azathioprine, and infliximab--before receiving a colectomy + ileal pouch anal anastamosis (IPAA) if the 3 medical therapy options were exhausted. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), defined as the difference of costs between strategies for each quality-adjusted life-year (QALY) gained. One-way sensitivity analyses were performed on variables to determine the key variables affecting cost-effectiveness.Standard medical care accrued a lifetime cost of $203,317 per patient, compared to $212,582 per patient for medical therapy + VSL#3. Lifetime QALYs gained was comparable for standard medical therapy and medical therapy + VSL#3 at 24.93 versus 25.05, respectively. Using the definition of ICER <50,000/QALY as a cost-effective intervention, medical therapy + VSL#3 produced an ICER of $79,910 per QALY gained, making this strategy cost-ineffective. Sensitivity analyses showed that 4 key parameters could affect the cost-effectiveness of the 2 strategies: cost of colectomy + IPAA, maintenance cost after surgery, probability of developing pouchitis after surgery, and the quality of life after a colectomy + IPAA. High surgical and postsurgical costs, a high probability of developing pouchitis, and a low quality of life after a colectomy + IPAA could make adjunct VSL#3 use a cost-effective strategy.Given present data, adjunct VSL#3 use for pediatric UC induction and maintenance of remission is not cost-effective, although several key parameters could make this strategy cost-effective. The quality of life after an IPAA is the single most important variable predicting whether this procedure benefits patients over escalating standard medical therapy.

View details for DOI 10.1097/MPG.0b013e3182293a5e

View details for Web of Science ID 000296383000007

View details for PubMedID 21694634

View details for Web of Science ID 000293251100393

Abstract

The United States spends more for healthcare than any other country in the world. With the rising prevalence of both Crohn's disease and ulcerative colitis, inflammatory bowel disease (IBD) represents the leading chronic gastrointestinal disease with increasing healthcare expenditures in the US. IBD costs have shifted from inpatient to outpatient care since the introduction of biologic therapies as the standard of care. Gastroenterologists need to be aware of the national cost burden of IBD and clinical practices that optimize cost-efficiency. This investigation offers a systematic review of the economics of IBD and evidence-based strategies for cost-effective management.

View details for DOI 10.1002/ibd.21488

View details for Web of Science ID 000292415200017

View details for PubMedID 21053357

Abstract

Rural status of patients may impact health before and after pediatric LT. We used UI codes published by the USDA to stratify patients as urban or rural depending county residence. A total of 388 patients who had LT and who met criteria were included. Rejection, PTLD, and survival were used as primary outcome measures of post-LT health. UNOS Status 1 and PELD/MELD scores >20 were used as secondary outcome measures of poorer pre-LT health. Logistic regression models were run to determine associations. We did not find any statistically significant differences in pre- or post-LT outcomes with respect to rurality. Among rural patients, there was a general trend for decreased incidence of rejection (25.0% vs. 33.4%; OR 0.64, 95% CI 0.29-1.44), increased risk of PTLD (5.6% vs. 3.4%; OR 1.86, 95% CI 0.36-3.31), and decreased survival (OR 0.85, 95% CI 0.34-2.13) after LT. Rural patients also tended to be sicker at the time of LT than patients from urban areas, with increased proportion of Status 1 (OR 1.17, 95% CI 0.51-2.70) and PELD/MELD scores >20 (OR 1.20, 95% CI 0.59-2.45). From a single center experience, we conclude that rurality did not significantly affect health outcomes after LT, although a larger study may validate the general trends that rural patients may have decreased rejection, increased PTLD, and mortality, and be in poorer health at the time of LT.

View details for DOI 10.1111/j.1399-3046.2010.01452.x

View details for Web of Science ID 000289628100018

View details for PubMedID 21450010

Abstract

Parenteral nutrition (PN), containing fat emulsions derived from soybean, has been implicated in the progression of PN-associated liver disease and cholestasis, particularly in infants with short bowel syndrome. Clinical use of Omegaven, a parenteral fish-oil emulsion, has been shown in recent studies to be a promising therapy to reverse liver disease and cholestasis. This review summarizes the rationale, relevant clinical investigations and future direction of Omegaven therapy for PN-dependent infants.

View details for DOI 10.1038/jp.2010.182

View details for Web of Science ID 000289236900009

View details for PubMedID 21448206

Abstract

Aluminum is a contaminant in all parenteral nutrition solutions. Manufacturers currently label these products with the maximum aluminum content at the time of expiry, but there are no published data to establish the actual measured concentration of aluminum in parenteral nutrition solution products prior to being compounded in the clinical setting. This investigation assessed quantitative aluminum content of products commonly used in the formulation of parenteral nutrition solutions. The objective of this study is to determine the best products to be used when compounding parenteral nutrition solutions (i.e., those with the least amount of aluminum contamination).All products available in the United States from all manufacturers used in the production of parenteral nutrition solutions were identified and collected. Three lots were collected for each identified product. Samples were quantitatively analyzed by Mayo Laboratories. These measured concentrations were then compared to the manufacturers' labeled concentration.Large lot-to-lot and manufacturer-to-manufacturer differences were noted for all products. Measured aluminum concentrations were less than manufacturer-labeled values for all products.The actual aluminum concentrations of all the parenteral nutrition solutions were significantly less than the aluminum content based on manufacturers' labels. These findings indicate that 1) the manufacturers should label their products with actual aluminum content at the time of product release rather than at the time of expiry, 2) that there are manufacturers whose products provide significantly less aluminum contamination than others, and 3) pharmacists can select products with the lowest amounts of aluminum contamination and reduce the aluminum exposure in their patients.

View details for DOI 10.5863/1551-6776-16.2.92

View details for PubMedID 22477831

View details for DOI 10.1007/s10620-010-1354-7

View details for Web of Science ID 000284066200006

View details for PubMedID 20683662