Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology
Improved Outcomes With Quality Improvement Interventions in Pediatric Inflammatory Bowel Disease
Samson, Charles M.*; Morgan, Pamela*; Williams, Elizabeth*; Beck, Lee*; Addie-Carson, RicJunette*; McIntire, Stacy†; Booth, Andrea†; Mendez, Eduardo†; Luzader, Carolyn†; Tomer, Gitit*; Saeed, Shehzad*; Donovan, Edward†; Bucuvalas, John*,†; Denson, Lee A.*
*Division of Gastroenterology, Hepatology, and Nutrition
†James M. Anderson Center for Health Systems Excellence, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Address correspondence and reprint requests to Charles M. Samson, MD, Division of Gastroenterology and Nutrition, Department of Pediatrics, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8116, St Louis, MO 63110 (e-mail: firstname.lastname@example.org).
Received 28 October, 2011
Accepted 3 May, 2012
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).
The authors report no conflicts of interest.
Objectives: Variations in chronic illness care are common in our health care system and may lead to suboptimal outcomes. Specifically, inconsistent use and suboptimal medication dosing have been demonstrated in the care of patients with inflammatory bowel disease (IBD). Quality improvement (QI) efforts have improved outcomes in conditions such as asthma and diabetes mellitus, but have not been well studied in IBD. We hypothesized that QI efforts would lead to improved outcomes in our pediatric IBD population.
Methods: A QI team was formed within our IBD center in 2005. By 2007, we began prospectively capturing physician global assessment (PGA) and patient-reported global assessment. Significant QI interventions included creating evidence-based medication guidelines, joining a national QI collaborative, initiation of preclinic planning, and monitoring serum 25-hydroxyvitamin D.
Results: From 2007 to 2010, 505 patients have been followed at our IBD center. During this time, the frequency of patients in clinical remission increased from 59% to 76% (P < 0.05), the frequency of patients who report that their global assessment is >7 increased from 69% to 80% (P < 0.05), and the frequency of patients with a Short Pediatric Crohn's Disease Activity Index (sPCDAI) <15 increased from 60% to 77% (P < 0.05). The frequency of repeat steroid use decreased from 17% to 10% (P < 0.05). We observed an association between the use of a vitamin D supplement (P = 0.02), serum 25-hydroxyvitamin D (P < 0.05), and quiescent disease activity.
Conclusions: Our results show that significant improvements in patient outcomes are associated with QI efforts that do not rely on new medication or therapies.
The Institute of Medicine published 2 reports in 2000 and 2001, To Err Is Human and Crossing the Quality Chasm, respectively, that highlighted a high frequency of medical errors within the US health care system and concluded that “between the health care we have and the care we could have lies not just a gap, but a chasm” (1,2). Since this time, numerous studies have been published that demonstrate a deficiency in the quality of care being delivered in our present health systems. In studies examining adherence to recommended care interventions, approximately 50% of both adult and pediatric patients were found to not receive indicated care, including care for acute or chronic conditions as well as appropriate preventative care (3,4). Quality improvement (QI) efforts have been shown to reduce variations in care delivery and improve care delivery processes and outcomes across a number of conditions (5–8).
Inflammatory bowel disease (IBD) represents a significant chronic illness with approximately 1 to 1.5 million people in the United States with this diagnosis and between 17,000 and 93,000 newly diagnosed patients each year (9,10). This patient population requires significant health care utilization, and a recent report estimated annual direct disease–attributable costs in the United States of >$5 billion (11,12). Several studies have examined variation in care of patients with IBD and have identified a need to address QI in their health care management. In both adult and pediatric studies, frequent underdosing of immunosuppressant medications has been reported with 40% to 60% of patients not receiving recommended initial dose or maximal dose in active patients (13,14). Furthermore, significant intercenter variation was found in use of medications in a multicenter pediatric cohort, which was consistent with 2 European surveys of gastroenterologists, which found significant differences in the use of immunomodulators (15–17). Knowledge regarding the effect of QI interventions in this population is, however, limited. A prospective study examining the effect of an IBD practice guideline at a single center showed only modest improvement in standardization of care and no difference in patient-reported outcomes between the intervention and control groups (18). The national pediatric IBD QI collaborative, ImproveCareNow (ICN), has reported preliminary results of 9 sites demonstrating increased reliability of growth, nutrition, disease severity assessment, and improved proportion of patients with Crohn disease in clinical remission that are followed through the collaborative (19); however, the key drivers of these improvement efforts have not yet been identified.
In the present study, we report the QI efforts undertaken and outcomes observed at a single academic pediatric gastroenterology practice. During a 4-year time period, we have observed an improvement in the frequency of our patients in clinical remission and corresponding improvements in patient-reported outcomes. Significant QI interventions have included organization of our clinical registry, prospective data capture at every IBD clinic visit, formation of an IBD QI team, creation and implementation of evidence-based medication guidelines, initiation of a previsit planning process, and fecal calprotectin monitoring. We also report increased monitoring of serum 25-hydroxyvitamin D (25-OHD) and the association between serum 25-OHD level and clinical remission.
Formation of Clinical Registry
In 2007, the Cincinnati Children's Hospital Medical Center (CCHMC) IBD clinical registry was initiated. All of the patients with IBD were assigned a specific colored chart after diagnosis. After this request was made by the care team, appropriate steps were taken so they would be enrolled within the clinical registry. In addition, after transitioning to an electronic health record (EHR) in October 2009, reports were generated showing all visits in the pediatric gastroenterology clinic that had a diagnosis code for Crohn disease, ulcerative colitis (UC), or IBD. For patients not yet enrolled in the registry table, primary care teams were contacted to confirm that patient had IBD and was appropriate for entry into the clinical registry. Patients were considered inactive from the registry if they transitioned to an adult care provider, if their primary IBD care was provided outside of CCHMC, or in patients with UC after colectomy.
Formation of the Cincinnati Children's IBD Center and QI Team
In 2001, the Schubert-Martin IBD Center was formed at CCHMC (Fig. 1). Following recruitment of the Center's medical and research directors in 2003, the IBD QI team was launched in 2005. An early task of the QI team focused on prioritizing efforts. The initial efforts considered included standardizing diagnostic evaluation, standardizing medication use and decreasing steroid use, optimizing nutritional assessment and management, preclinic planning, and finally promoting family and patients’ self-management. Determining which efforts that would take priority was accomplished by discussing 16 medical scenarios, which had varied focus of the above 5 interventions. After this analysis, it was determined to initially work on standardizing medication use with an aim of subsequently decreasing steroid use. A multidisciplinary group subsequently developed evidence-based guidelines for the use of 6-mercaptopurine (6-MP), infliximab, and methotrexate (MTX) that were implemented in 2007 and widely used starting in 2008 (supplemental Fig. 1, http://links.lww.com/MPG/A123) (20). Also during this time period, clinic forms were designed that could prospectively and systematically capture the PGA and patient/parent self-report of global assessment and confidence in managing their disease at each IBD clinic visit (supplemental Fig. 2 [http://links.lww.com/MPG/A124] and supplemental Fig. 3 [http://links.lww.com/MPG/A125]). Data infrastructure resources were implemented and data from these forms were entered into a local data registry so measures of remission rate and patient-reported outcomes could be followed monthly. These clinic forms were used until October 2009, when the electronic medical record (EMR) EPIC was implemented in the outpatient gastroenterology clinic at CCHMC. Using the clinic forms as templates, several EPIC documentation flow sheets were created such that these data items would be entered discretely at the point of care and avoid the need for separate data entry into the registry (supplemental Fig. 4 [http://links.lww.com/MPG/A126] and supplemental Fig. 5 [http://links.lww.com/MPG/A127]).
In 2007, CCHMC was 1 of the original 10 pediatric gastroenterology sites to join the national QI collaborative PIBDNet Trailblazer Improvement Collaborative (now named ICN) (21). The global aim for the collaborative has been to build a sustainable network that improves the outcomes of care for children with IBD. To aid the CCHMC QI efforts, an embedded quality improvement consultant (QIC) for the gastroenterology division was recruited in 2009.
Beginning in 2007, the IBD QI team began receiving support from the CCHMC Disease Specific Innovations & Outcomes Program (DSIOP) team. This team assisted in establishing our data infrastructure, developing processes to ensure data quality, and assisting in the adoption of the ICN tools for previsit planning to CCHMC. Starting in June 2009, all of the patients who had an active disease activity at their preceding clinic visit were reviewed the week before their follow-up clinic visit by a multidisciplinary team including an attending pediatric gastroenterologist, the IBD nurse/program manager, the divisional QIC, and IBD research coordinator. Patient charts were systematically reviewed to determine if maintenance medication doses were appropriate, if appropriate drug levels had been measured, if appropriate screening laboratories were up to date, if the patient was taking prednisone (and if so if a taper was documented), if the patient was eligible for an ongoing research study, and, finally, if a referral to psychology or the CCHMC Adherence center may be indicated. These recommendations were forwarded to the appropriate nurse-physician care team before the patients’ visit. After the division began using EPIC, a clarity report was designed that incorporated data from the EMR that were used to aid in the preclinic planning process (supplemental Fig. 6 [http://links.lww.com/MPG/A128]). Following initial success with the process, in addition to continuing to review the active patients, all of the patients seen by 2 of the providers within the CCHMC IBD center underwent the preclinic planning process with the specific physician-nurse team that would be seeing the patient the following week. This resulted in approximately 50% to 60% of patients with IBD being seen the following week having previsit planning completed.
Outcome Measures and Retrospective Chart Review
A retrospective chart review of all of the patients in the IBD clinical registry was approved by the CCHMC institutional review board and patient charts were reviewed from January 1, 2007, to December 31, 2010. From January 2007 to October 2009, IBD-specific clinic paper forms were used to systematically capture the physician global assessment (PGA) and patient-/parent-reported outcomes at each IBD outpatient visit. For the PGA, physicians indicated whether patients had quiescent, mild, moderate, or severe disease activity. To improve the standardization of PGA classification, definitions for these categories that were developed by ICN were circulated intermittently to the care providers (supplemental Fig. 7 [http://links.lww.com/MPG/A129]). The remission rate was defined as the percent of patients with a PGA of quiescent at their most recent visit. Patients were considered to have inactive disease if the PGA was indicated as quiescent and active disease for all other values of the PGA. For patient-reported outcomes, patient responses were used if patients were ≥9 years at the time of the visit and parent responses were used for patients <9 years of age. Patient-/parent-reported outcomes obtained included a patient global assessment measure, which was determined by asking the patient and parent “How do you feel today?” and a second patient-reported outcome of “How confident are you in managing your disease?” Both questions were answered on a 10-point Likert scale. After October 2009, the PGA and patient-reported data were collected in discrete data fields within the patient's EMR. Charts were reviewed and data were taken from the visit in each year from 2007 to 2010 that was closest to December 31. If patients were not seen during a specified calendar year, they were excluded from the corresponding year's analysis; however, they were included in following years should they have subsequently returned (supplemental Fig. 8 [http://links.lww.com/MPG/A130]).
Data collected from each visit included the PGA, the patient-/parent-reported global assessment and confidence in managing their disease, dosages of 6-MP/azathioprine, MTX, infliximab, 5-aminosalycilate (5-ASA), vitamin D supplement, and prednisone. In addition, patients’ clinical laboratory reports were reviewed and values for fecal calprotectin, serum 25-OHD, 6-thioguanine level (6-TGN), and infliximab levels were recorded. For patients with multiple values in a given year, the result with a date closest to December 31 of each year was used for analysis.
Discrete data elements were extracted from either the local clinical data registry (2007–2009) or the EMR (2010) to calculate the Short Pediatric Crohn's Disease Activity Index (sPCDAI) and the Pediatric Ulcerative Colitis Activity Index (PUCAI), as described (22,23). We used the established cutoff points of a total score <15 and <10 to define remission for the sPCDAI and PUCAI, respectively.
For the outcome measures of remission rate, disease activity indices, patient-reported outcomes, and steroid use, patients were excluded from the measure if the appropriate data were missing at the specified clinic visit or if they had been diagnosed for <112 days at the time of the clinic visit.
Statistical analyses were performed using GraphPad PRISM version 5.02 (GraphPad Inc, San Diego, CA) and SPSS version 20 (SPSS Inc, Chicago, IL). Continuous variables were analyzed using 2-sample t test and 1-way ANOVA with Bonferroni test for multiple comparisons. Discrete variables were analyzed using the Fisher exact test or chi square analysis with Marascuilo procedure for multiple comparisons. Spearman correlation coefficient was used to assess the relations between patient/parent global assessment and PGA, between the sPCDAI score and PGA, and between the PUCAI score and PGA. Correlation between serum 25-OHD level and remission rate was analyzed using the chi-square test for trend. Results were considered statistically significant for P values ≤0.05.
Improvements in Remission Rate, Patient-/Parent-reported Outcomes, and Disease Activity Indices
From 2007 to 2010, 505 pediatric patients with IBD were followed at the CCHMC IBD center. Fifty-four percent were boys; the mean (standard deviation [SD]) age at diagnosis was 11 ± 4 years and 70% had a diagnosis of Crohn disease. The percentage of patients with Crohn disease and percentage of male patients did not change during the course of the study (supplemental Table 1 [http://links.lww.com/MPG/A131]). The average age and duration of disease increased by 1.6 and 0.8 years, respectively, between 2007 and 2010. In addition, the number of patients seen in a given year increased from 250 in 2007 to 450 in 2010 (supplemental Fig. 8, http://links.lww.com/MPG/A130). Initially captured on IBD-specific clinic forms and starting in October 2009 on EPIC documentation flow sheets, PGA and patient/parent self-report of global assessment and confidence in managing their disease were assessed at each IBD clinic visit. From December 2007 to December 2010, the remission rate of the population increased from 59% to 76% (P < 0.05, Fig. 2A). Corresponding to the improvement in the physician-reported remission rate, the frequency of patients reporting a global assessment >7 increased from 69% to 80% and the frequency of patients reporting confidence in managing their disease >7 increased from 77% to 88% (P < 0.05, Fig. 2B and C). There was a significant correlation between PGA and the patient/parent global assessment (r = −0.40, P < 0.01) with significant differences in the mean value of the patient/parent global assessment among the three PGA classifications (P < 0.0001) (Fig. 2D). Neither physician nor patient-/parent-reported outcomes varied between patients with Crohn disease and UC (supplemental Table 2, http://links.lww.com/MPG/A132).
In addition to improvements in these physician and patient-reported outcomes, there were also improvements in the frequency of patients in remission as defined by a pediatric Crohn disease clinical disease index, the sPCDAI. For patients with CD, the percentage of patients with a sPCDAI <15 increased from 60% to 77% (Fig. 3A). As others have reported, we also observed a significant correlation between the PGA and the sPCDAI score (r = 0.65, P < 0.01) with an overall sensitivity of 70% and specificity of 84% of determining who had active disease based on the PGA (Fig. 3B) (22). Similarly for patients with UC, there was a trend toward the percentage of patients with a PUCAI <10 increased from 54% to 70%, although this did not reach statistical significance (P = 0.24, Fig. 3C). There was a statistically significant correlation between the PGA and the PUCAI score (r = 0.65, P < 0.01) (Fig. 3D). Our overall sensitivity and specificity of the PUCAI for determining who had active disease based on the PGA was 84% and 80%, respectively.
Stable Immunomodulator Use and Decreased Use of Prednisone
To determine what changes may have been associated with the observed improvements in the remission rate and patient-reported outcomes, patient charts were reviewed to determine which immunomodulators were prescribed, the medication doses used, and if patients were taking prednisone. There were no statistically significant differences observed in the frequency of patients receiving 5-ASA, 6-MP, anti-tumor necrosis factor-alpha (anti-TNF-α) inhibitors, or MTX within the time period studied among the entire population (Table 1). There was a trend toward the increased use of anti-TNF-α therapy and the decreased use of 6-MP between 2007 and 2010 in the general population that did not reach statistical significance. Within the population of patients with Crohn disease, however, there was a statistically significant decrease in the use of 6-MP between 2007 and 2010, with a trend toward increased anti-TNF-α therapy use. Within the UC population, there were trends toward increased use of 5-ASA, 6-MP, and anti-TNF-α therapy, although none reached statistical significance. The proportion of patients with inactive disease activity did not vary by medication prescribed at any time between 2007 and 2010 (data not shown). There was no difference in the mean weight based dosing of these drug classes, with the exception of 5-ASA wherein the average dose increased from 42 ± 1 to 50 ± 1 mg/kg between 2007 and 2010 (P = 0.001). Furthermore, the frequency of patients taking a 6-MP dose >1 mg/kg (or for heterozygote thiopurine methyltransferase metabolizers a dose >0.5 mg/kg) in 2007 was 80%, taking an infliximab dose >4.5 mg/kg in 2007 was 90% or an MTX dose >12.5 mg/m2 in 2007 was 78%. These did not significantly change over the time period studied (data not shown). Although the frequency of patients taking 6-MP who had 6-TGN metabolites measured did not change, the frequency of patients taking infliximab who had an infliximab level measured increased in 2009 and 2010 compared with 2007 and 2008 (Fig. 4). Although no change was observed in the frequency of patients on immunomodulators, a statistically significant decrease in the frequency of patients receiving prednisone beyond 112 days from diagnosis was observed between December 2007 and December 2010 (Table 1). Therefore, we observed a decreased use of corticosteroids while increasing the population's remission rate and patient-reported global assessment and confidence in managing their disease.
Increased Use of Fecal Calprotectin Monitoring
Fecal calprotectin has been shown to be a sensitive biomarker for detecting active mucosal disease in patients with IBD and correlates with endoscopic disease activity (24–28). Beginning in 2009, the IBD team recommended that patients with IBD at CCHMC with inactive disease have fecal calprotectin monitored every 6 months, with therapeutic drug monitoring implemented for patients with elevated fecal calprotectin. After this recommendation, we observed an increase in the frequency of patients with a fecal calprotectin measured in 2009 and 2010 (Fig. 5A). It has been shown that a fecal calprotectin >400 μg/g is associated with a higher chance of relapse in a pediatric cohort (29). We found that between 2007 and 2010 the average fecal calprotectin within our population was significantly decreased and the frequency of patients with a fecal calprotectin <400 μg/g correspondingly increased (Fig. 5A). Furthermore, similar to published data, we found that of patients with quiescent disease activity in 2009 a fecal calprotectin >400 μg/g was significantly associated with having active disease in 2010 with an odds ratio of 4.1 (1.02–16.47) (29). For those patients with quiescent disease in 2009, the mean calprotectin in 2009 of those patients who subsequently had active disease in 2010 was statistically significantly higher than those patients who remained in remission in 2010 (Fig. 5C). Therefore, an elevated fecal calprotectin in patients with inactive disease in 2009 correlated with active disease in the subsequent year.
Serum 25-OHD Monitoring and Treatment
Vitamin D deficiency is common in patients with IBD (30–32). Given its well-known seasonal variation, beginning in 2009, it was recommended that patients with IBD followed at CCHMC have their serum 25-OHD level measured every 6 months. If a patient's serum 25-OHD level was <30 ng/mL, it was recommended that patients should be started taking ergocalciferol 50,000 U (8000 U for patients weighing <20 kg) weekly for 6 to 8 weeks before rechecking the serum 25-OHD level. Once a serum 25-OHD level of 30 ng/mL had been achieved, it was recommended that patients be maintained on monthly ergocalciferol dosing. Based on this recommendation, there was a significant increase in the frequency of patients who had their serum 25-OHD measured and who received a vitamin D supplement (Fig. 6A). The average dose for patients taking a vitamin D supplement increased between 2007 and 2010 (Fig. 6B). The new Institute of Medicine report recommends using a serum 25-OHD value of 20 ng/mL to define vitamin D deficiency and new NASPGHAN guidelines discuss using values of 20 and 32 ng/mL as levels to guide vitamin D replacement recommendations (33,34). With our interventions, the average serum 25-OHD level increased in our population between 2008 and 2010 and the frequency of patients with a value >32 ng/mL increased, whereas the frequency of patients with a value <20 ng/mL decreased (Fig. 6C and D).
We observed an association between vitamin D supplementation and disease activity status. In 2010, the frequency of inactive disease was higher in patients taking a vitamin D supplement compared with those patients not taking a vitamin D supplement (Fig. 7A). Accordingly, the mean serum 25-OHD level was higher in patients with inactive disease activity compared with patients with active disease (Fig. 7B). There was also a statistically significant association between the serum 25-OHD level and disease activity, with patients with higher serum 25-OHD levels exhibiting a higher rate of inactive disease (Fig. 7C). Furthermore, for those patients with quiescent disease activity in 2009 who had a serum 25-OHD level obtained, a serum level <20 ng/mL was statistically significantly associated with having active disease in 2010 with an odds ratio of 3.0 (1.1, 8.0), compared with those patients who had a serum level >20 ng/mL. Similar to an elevated fecal calprotectin, a low serum 25-OHD in patients with clinical inactive disease activity was associated with having active disease in the subsequent year.
Since we began systematically and prospectively tracking outcomes of our patients with IBD in 2007, we have observed a significant improvement in the proportion of our patients in remission with a quiescent PGA and decrease in steroid use. Corresponding to this improvement in clinician-reported outcomes, we have also observed improvements in 2 patient/parent self-report measures of global assessment and confidence in disease management as well as an increase in patients with Crohn disease in remission as defined by the sPCDAI. Several interventions occurred during this time period that were associated with outcome improvements. These include the development and use of evidence-based medication guidelines, support from an institutional-based QI program (DSIOP), participation in a national QI collaborative (ICN), initiation of a preclinic planning process, monitoring of disease activity with a fecal biomarker, and active monitoring and supplementation of vitamin D.
Variation in care can lead to unwarranted differences in effective care and patient safety that can cause significant differences in patient outcomes (35). To standardize care among the patients seen by the approximately 20 individual practitioners at our institution, evidence-based guidelines were created and implemented throughout our practice. After these guidelines were widely distributed, we did not observe significant changes in dosing of 6-MP, infliximab, or MTX; however, we did observe a decrease in the frequency of patients taking corticosteroids beyond 112 days from diagnosis, and an increase in the use of serum infliximab measurements. These data are consistent with the finding in an adult IBD center that found only modest improvements in adherence to their evidence-based guideline after implementation (18). One explanation that has been given for this finding is the heterogeneity of the IBD population and the reluctance for physicians to use care guidelines. In a qualitative interview study with 17 adult gastroenterologists, only 1 physician reported the regular use of an IBD practice guideline (36). On the contrary, compared with the findings from a multicenter pediatric prospective cohort that found that 46% of patients were taking a lower than the recommended target thiopurine dose and an adult study that showed that 82% of active second opinion patients with IBD were taking a suboptimal 6-MP dose, our cohort in 2007 already had 80% of patients with a thiopurine dose within the target range and this high baseline likely had an influence on the additional effect our medication guidelines would have (13,14).
QI efforts have been shown to improve both process and outcome measures in a variety of conditions including cystic fibrosis, adults with diabetes mellitus, congestive heart failure, asthma, transplant medication monitoring, and preventative care (5–7,37,38). In 2007, we were one of the original sites in the national pediatric IBD QI collaborative, ICN (21). Although our center's data were not included in the initial reporting of outcome data, our improvement in remission rates are consistent with the finding that sites involved in ICN had remission rates of patients with Crohn disease increase from 48% in 2007 to 64% in 2009 (19). Preclinic planning was an intervention initially discussed through the ICN collaborative, and was implemented in a manner to fit the needs of our center in 2009. The initiation of preclinic planning corresponds to when our remission rate increased from 67% in 2009 to 76% in 2010. The mechanism for this change is unknown, but as a part of this change in delivery system, recommendations to monitor fecal calprotectin, implement 6-TGN and infliximab level monitoring in patients with active disease or elevated fecal calprotectin, and correct vitamin D deficiency were implemented. Of note, during this time frame there was no further improvement in our patient-reported outcomes. To further address this, new QI activities are focusing on patient/parent self-management skills as well as involving the patient/parent in the preclinic planning process.
Fecal calprotectin has been shown to be a biomarker that may be useful in assessing disease activity and mucosal healing (27). It has been shown that there is a high association between fecal calprotectin and endoscopic severity scores (39). Therefore, this biomarker may be helpful to identify symptoms that are related to postinflammatory irritable bowel syndrome and/or gauge response to treatment (28). In 15 patients on exclusive enteral nutrition, a decrease of calprotectin >18% after 30 days on therapy predicted clinical response at the end of treatment (40). In both adult and pediatric studies, patients in clinical remission with an elevated fecal calprotectin had an increased risk of developing relapse during the next 6 to 12 months (29,41–43). Although we did observe a decrease in both the mean fecal calprotectin level in our population and the frequency of patients with a fecal calprotectin >400 μg/g, some of this change is likely the result of measuring this biomarker in patients in remission. Nevertheless, our findings that an elevated fecal calprotectin in clinically inactive patients is associated with active disease in the subsequent year supports is consistent with the published literature, and moving forward it will be important to confirm prospectively whether reduction in fecal calprotectin is associated with lower rates of relapse in our overall patient population. Also, as this was a retrospective study, we could not determine how clinicians responded to an elevated fecal calprotectin level and the effect this may have had on future disease activity and therefore will be important to capture prospectively in the future.
The final intervention made during the time period wherein improvement in outcomes was observed was the implementation of a guideline to monitor for and correct vitamin D deficiency. Compared with 2007 when fewer than 5% of patients had a serum 25-OHD measured, by 2010 the levels were measured for >80% of patients. Consistent with previous reports, a significant proportion of our patients were vitamin D deficient, defined by a serum 25-OHD <20 ng/mL (30–32,44,45). We found that patients taking a vitamin D supplement were more likely to be in clinical remission compared with patients not taking a vitamin D supplement. This is consistent with a recent randomized controlled trial in 108 adult patients with Crohn disease in remission in which patients receiving a vitamin D3 supplement exhibited a trend toward a 2-fold lower relapse rate during 1 year of follow-up (46). Furthermore, when our patients were stratified by serum 25-OHD level, there was a significant correlation between remission rate and their serum 25-OHD level. Also, we found that a low serum 25-OHD level in clinically inactive patients is associated with active disease in the subsequent year. The mechanism by which vitamin D may modulate IBD activity is unknown, although in vitro studies performed on T cells isolated from patients with IBD have shown that vitamin D may modulate the TH1/TH2 response and/or increase interleukin-10 production (47,48). It is also possible that serum 25-OHD is an indicator of adherence or that vitamin D supplementation in our population may be a marker for more attentive care, so further randomized, placebo-controlled studies examining the use of ergocalciferol as an adjunctive treatment in IBD may be indicated.
There are several limitations that should be noted regarding our findings. First, we recognize that PGA as assigned by clinicians can be subjective and is the basis for 1 of the outcome measures for which we observed improvements; however, the data were captured prospectively and to aid in uniformity, guidelines for PGA were distributed to the faculty to help consistency among a large number of clinicians. Although these guidelines were not systematically recirculated at specific time intervals, intermittently providers were shown how their specific patient-reported outcomes correlated with their PGA classification and were provided additional copies of the classifications at this time. In addition, corresponding to the improvements in physician assessment and outcome, we reassuringly also observed improvement in 2 patient-reported outcomes. These patient-based outcomes are unique to our study and presently not included in multicenter collaborative's measures (49). Also to strengthen our study, we included calculation of the validated disease activity scores, the sPCDAI and PUCAI, which showed similar improvements as our physician and patient-/parent-reported outcomes. In addition, there were significant correlations between the PGA and patient-reported outcomes and between the PGA and disease activity indices. Our physician and patient-reported outcomes, as well as disease activity indices, only represent a single time point within a given year. Although because this method was used in all years of our study and would not expect any bias secondary to this method of calculating outcome measures, we along with the national QI IBD collaborative recognize the utility of defining sustained remission and have recently started collecting data that will define the percentage of patients with no reported relapses during a 12-month time period. Monthly monitoring of both the standard clinical remission rate and sustained remission is ongoing. Also, we recognize that is difficult to determine which intervention was specifically associated with the improvement in patient outcomes. The QI initiatives began at the same time as PGA and patient data were systematically collected; therefore, previous outcome data for our population is unavailable. Also, because several interventions were made during the time period, it is difficult to know if one intervention had more effect than another. To strengthen the reporting of our findings, we have attempted to conform to the Standards for Quality Improvement Reporting Excellence guidelines, which outlines suggested criteria for QI publication guidelines (50). These guidelines range from stating the primary improvement goal, describing the environment in which improvements took place and how and why changes were implemented, describing the methods of evaluation and analysis of the outcome and process measures, and, lastly, interpreting the results and addressing limitations of the study. Finally, our results do demonstrate only a single center's experience and therefore generalizability should be considered; however, the large population of our center strengthens our results with a high follow-up rate, and although our practice is located at tertiary medical center, we are the only pediatric gastroenterologists in the metropolitan area and therefore our population should be reflective of a general patient population with IBD. Finally, the trends observed at our center are consistent with improvement at other sites within the pediatric IBD QI collaborative during the same time.
In summary, we have reported significant improvement in the outcomes, both physician and patient-/parent-reported, as well as in remission rates as defined by validated sPCDAI, of the pediatric patients with IBD followed at our center. These improved outcomes were captured by prospective collection of data at every patient with IBD visit and were associated with several QI interventions including distribution and implementation of evidence-based care guidelines, involvement in the national QI collaborative, ICN, and initiation of preclinic planning. Other significant changes in the recommended care our patients receive included routine monitoring of fecal calprotectin and vitamin D status. Our results show that significant improvement in patient outcomes were achieved following QI efforts that did not rely on new medication or therapies, rather through initiating novel care processes and standardization of care.
We thank the physicians, nurses, and patients in our practice who were helpful in testing the QI methods implemented at CCHMC. We appreciate the divisional and institutional financial support that made our QI efforts possible. We also thank all of the participating members in the ICN QI collaborative, who we have benefitted from working with and learning from. We also are thankful for the support we receive from our IBD research coordinators, Ramona Bezold and Kathleen Lake, and data entry support from Denise Strong.
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care guidelines; chronic illness; fecal calprotectin; serum 25-OHD; vitamin D
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