Routine use of thiopurines in maintaining remission in pediatric Crohn's disease.

AIM: To evaluate the effectiveness of thiopurines in maintaining steroid-free remission in routine clinical practice. METHODS: The multi-center Pediatric Inflammatory Bowel Disease Network (PIBDNet) cohort study prospectively collected data on thiopurine naïve patients initiating mercaptopurine (6MP) or azathioprine. Patients with a diagnosis of Crohn's disease (CD) were included in our study upon entering remission as determined by physician global assessment (PGA) within 365 d of initiation of thiopurines. The primary outcome of the study was maintenance of steroid-free remission (SFR) at each follow up visit. Patients were considered treatment failures if there had been a change in PGA from remission to mild, moderate or severe disease; disease relapse between visits; need for rescue therapy (biologic therapy, methotrexate, steroids); thiopurine discontinuation, hospitalization or surgical intervention. A secondary outcome defined treatment failure as a change from remission to moderate or severe (not mild) in addition to the previously defined criteria. RESULTS: Sixty-five of 182 patients in the PIBDNet registry met criteria for inclusion in this study. Forty-five of 65 (69%) of included patients achieved remission within 180 d of thiopurine initiation. For the primary outcome, 47% and 23% of patients remained in SFR at 6 and 12 mo. The mean thiopurine dose at initiation for the 65 included patients was 0.89 ± 0.31 mg/kg per day. Metabolite levels were obtained in 48% (31/65) of the included patients with a mean 6TG level of 258 pmole/8 × 10(8) RBC ± 147. For the secondary outcome, 65% and 42% of patients remained in SFR at 6 and 12 mo. CONCLUSION: Thiopurines were less effective in maintaining remission for pediatric CD in this "real world" cohort than has been previously described. Variation in thiopurine dosing and metabolite measurement was found among practitioners.

Effectiveness of anti-TNFα for Crohn disease: research in a pediatric learning health system.

OBJECTIVES: ImproveCareNow (ICN) is the largest pediatric learning health system in the nation and started as a quality improvement collaborative. To test the feasibility and validity of using ICN data for clinical research, we evaluated the effectiveness of anti-tumor necrosis factor-α (anti-TNFα) agents in the management of pediatric Crohn disease (CD). METHODS: Data were collected in 35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed as a sequence of nonrandomized trials. Patients who had moderate to severe CD were classified as initiators or non-initiators of anti-TNFα therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFα therapy on entry into ICN. RESULTS: During a 26-week follow-up period, rate ratios obtained from Cox proportional hazards models, adjusting for patient and disease characteristics and concurrent medications, were 1.53 (95% confidence interval [CI], 1.20-1.96) for clinical remission and 1.74 (95% CI, 1.33-2.29) for corticosteroid-free remission. The rate ratio for corticosteroid-free remission was comparable to the estimate produced by the adult SONIC study, which was a randomized controlled trial on the efficacy of anti-TNFα therapy. The number needed to treat was 5.2 (95% CI, 3.4-11.1) for clinical remission and 5.0 (95% CI, 3.4-10.0) for corticosteroid-free remission. CONCLUSIONS: In routine pediatric gastroenterology practice settings, anti-TNFα therapy was effective at achieving clinical and corticosteroid-free remission for patients who had Crohn disease. Using data from the ICN learning health system for the purpose of observational research is feasible and produces valuable new knowledge.

PEDSnet: a National Pediatric Learning Health System.

A learning health system (LHS) integrates research done in routine care settings, structured data capture during every encounter, and quality improvement processes to rapidly implement advances in new knowledge, all with active and meaningful patient participation. While disease-specific pediatric LHSs have shown tremendous impact on improved clinical outcomes, a national digital architecture to rapidly implement LHSs across multiple pediatric conditions does not exist. PEDSnet is a clinical data research network that provides the infrastructure to support a national pediatric LHS. A consortium consisting of PEDSnet, which includes eight academic medical centers, two existing disease-specific pediatric networks, and two national data partners form the initial partners in the National Pediatric Learning Health System (NPLHS). PEDSnet is implementing a flexible dual data architecture that incorporates two widely used data models and national terminology standards to support multi-institutional data integration, cohort discovery, and advanced analytics that enable rapid learning.

Multi-Institutional Sharing of Electronic Health Record Data to Assess Childhood Obesity.

OBJECTIVE: To evaluate the validity of multi-institutional electronic health record (EHR) data sharing for surveillance and study of childhood obesity. METHODS: We conducted a non-concurrent cohort study of 528,340 children with outpatient visits to six pediatric academic medical centers during 2007-08, with sufficient data in the EHR for body mass index (BMI) assessment. EHR data were compared with data from the 2007-08 National Health and Nutrition Examination Survey (NHANES). RESULTS: Among children 2-17 years, BMI was evaluable for 1,398,655 visits (56%). The EHR dataset contained over 6,000 BMI measurements per month of age up to 16 years, yielding precise estimates of BMI. In the EHR dataset, 18% of children were obese versus 18% in NHANES, while 35% were obese or overweight versus 34% in NHANES. BMI for an individual was highly reliable over time (intraclass correlation coefficient 0.90 for obese children and 0.97 for all children). Only 14% of visits with measured obesity (BMI ≥95%) had a diagnosis of obesity recorded, and only 20% of children with measured obesity had the diagnosis documented during the study period. Obese children had higher primary care (4.8 versus 4.0 visits, p<0.001) and specialty care (3.7 versus 2.7 visits, p<0.001) utilization than non-obese counterparts, and higher prevalence of diverse co-morbidities. The cohort size in the EHR dataset permitted detection of associations with rare diagnoses. Data sharing did not require investment of extensive institutional resources, yet yielded high data quality. CONCLUSIONS: Multi-institutional EHR data sharing is a promising, feasible, and valid approach for population health surveillance. It provides a valuable complement to more resource-intensive national surveys, particularly for iterative surveillance and quality improvement. Low rates of obesity diagnosis present a significant obstacle to surveillance and quality improvement for care of children with obesity.

Short pediatric Crohn's disease activity index for quality improvement and observational research.

BACKGROUND: Practical and objective instruments to assess pediatric Crohn's disease (CD) activity are required for observational research and quality improvement. The objectives were: 1) to determine the feasibility of completing the Pediatric Crohn's Disease Activity Index (PCDAI) and the Abbreviated PCDAI (APCDAI); and 2) to create a Short PCDAI by retaining and reweighting the most practical and informative components. METHODS: Physicians in the ImproveCareNow Collaborative for pediatric inflammatory bowel disease (IBD) were asked to record components of the PCDAI and assign a Physician Global Assessment (PGA) of disease severity at each patient encounter. We assessed the feasibility of the PCDAI, the APCDAI, and the individual index components by determining the proportion of visits in which data were recorded. We created a short index by retaining and reweighting components of the PCDAI completed in ≥80% of visits. The feasibility of the Short PCDAI and its ability to discriminate between PGA categories were evaluated using descriptive statistics. RESULTS: This study population included 1355 subjects with CD (6373 visits). The PCDAI and APCDAI were complete in 16.7% and 44.1% of visits, respectively. A Short PCDAI, including general well-being, abdominal pain, stools, weight, abdominal exam, and extraintestinal manifestations were completed in 66.5% of visits. The correlation between the Short PCDAI and PGA was similar to that of the PCDAI (r = 0.60, P < 0.001 versus 0.61, P < 0.001). CONCLUSIONS: The Short PCDAI is a practical and valid tool to measure pediatric CD activity. Its use should facilitate quality improvement and observational research.

A method for understanding some consequences of bringing patient-generated data into health care delivery.

OBJECTIVE: The consequences of personal health record (PHR) phenomena on the health care system are poorly understood. This research measures one aspect of the phenomena--the time-cost impact of patient-generated data (PGD) using discrete event model (DEM) simulation. BACKGROUND/SIGNIFICANCE: Little has been written about the temporal and cognitive burden associated with new workflows that include PGD. This pilot study reports the results for time-cost and resource utilization of a ''typical'' ambulatory clinic under varying conditions of PGD burden. METHODS: PGD effects are modeled with DEM simulation reflecting the sequential relationships, temporal coupling, and impact assumptions within a virtual clinic. Three simulation scenarios of ever-increasing PGD impact are compared to a baseline case of no PGD use. RESULTS: Introduction of PGD resulted in expected increases in cost and resource utilization along with a few key exceptions and unanticipated consequences. Direct and indirect impacts were observed with notable nonlinear, nonadditive, disproportionate, heterogeneous aspects and interactions among consequent labor cost, visit length, workday length, and resource utilization. The middle-impact simulations showed a 29% increase in daily labor costs and 28% shrinkage of the margin between revenues and labor costs. Lengths of both workday and patient visit were extended and less predictable with PGD use. Utilization rates of most staff positions rose. Nurse utilization rates showed greatest increases. Physicians' utilization rates paradoxically stayed relatively unchanged. CONCLUSION: This analysis contributes to an understanding of the effects of PGD on time and cognitive burdens of physicians, staff, and physical resources. It illustrates the usefulness of DEM simulation for the purpose. Avoidable consequences are exposed quantifiably for both the patient and the clinic. More realistic ways to respond to PGD impact are needed.

Variation in care in pediatric Crohn disease.

OBJECTIVES: Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists. METHODS: Two hundred forty-six Crohn disease patients of 93 pediatric gastroenterologists from 48 practice sites starting treatment with either thiopurine or infliximab were studied. We assessed variation in diagnostic testing that had been performed to establish the diagnosis of Crohn disease and to assess the phenotype, extent, and severity of disease. We also assessed variation in initial thiopurine and infliximab dosage and in nutritional therapy. RESULTS: Diagnostic studies in which care was uniform included complete blood count, performed in 100% of patients, erythrocyte sedimentation rate and colonoscopy in 96%, and upper endoscopy in 89%. However, imaging of the small bowel had not been performed in 19%, and a stool test for pathogens had not been performed in 29%. Thiopurine methyltransferase (TPMT) had been measured in 61% of patients before treatment with a thiopurine; in 85%, TPMT was normal. Nonetheless, even when TPMT was normal, 40% of patients received an initial dose of thiopurine that was lower than recommended. Testing for tuberculosis before initiating treatment with infliximab was not performed in 30%. In addition, 36% of severely underweight patients were not receiving a multivitamin supplement, supplemental formula, or tube feeding. CONCLUSIONS: There is variation in diagnostic and therapeutic interventions in the management of pediatric Crohn disease, and gaps exist between recommended and actual care.