AGA clinical practice guideline on the role of biomarkers for the management of Crohn's Disease

Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease.

BACKGROUND & AIMS: Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. RESULTS: The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. CONCLUSIONS: In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.

AGA clinical practice guideline on the role of biomarkers for the management of ulcerative colitis

Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC. A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis on the clinical performance of serum C-reactive protein (CRP), fecal calprotectin, and fecal lactoferrin as biomarkers of disease activity in patients with established UC in symptomatic remission or with active symptoms. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of biomarkers for monitoring and management of UC and provided implementation considerations for clinical practice. The guideline panel made 7 conditional recommendations. In patients with UC in symptomatic remission, the panel suggests the use of a biomarker- and symptom-based monitoring strategy over a symptom-based monitoring strategy. For patients in symptomatic remission, the panel suggests using fecal calprotectin <150 µg/g, normal fecal lactoferrin, and/or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease. In patients with UC with moderate to severe symptoms, the panel suggests using fecal calprotectin >150 µg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease. However, in patients in symptomatic remission but elevated biomarkers, and in patients with moderate to severe symptoms with normal biomarkers, the panel suggests endoscopic assessment of disease to inform treatment decisions. In patients with UC with mild symptoms, the panel suggests endoscopic assessment of disease activity to inform treatment decisions. The panel identified the use of a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy as a knowledge gap. The panel also proposed key implementation considerations for optimal use of biomarkers, and identified areas for future research. In patients with UC, noninvasive biomarkers, including fecal calprotectin, fecal lactoferrin, and serum CRP can inform disease monitoring and management.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis.

BACKGROUND & AIMS: Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis on the clinical performance of serum C-reactive protein (CRP), fecal calprotectin, and fecal lactoferrin as biomarkers of disease activity in patients with established UC in symptomatic remission or with active symptoms. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of biomarkers for monitoring and management of UC and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 conditional recommendations. In patients with UC in symptomatic remission, the panel suggests the use of a biomarker- and symptom-based monitoring strategy over a symptom-based monitoring strategy. For patients in symptomatic remission, the panel suggests using fecal calprotectin <150 µg/g, normal fecal lactoferrin, and/or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease. In patients with UC with moderate to severe symptoms, the panel suggests using fecal calprotectin >150 µg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease. However, in patients in symptomatic remission but elevated biomarkers, and in patients with moderate to severe symptoms with normal biomarkers, the panel suggests endoscopic assessment of disease to inform treatment decisions. In patients with UC with mild symptoms, the panel suggests endoscopic assessment of disease activity to inform treatment decisions. The panel identified the use of a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy as a knowledge gap. The panel also proposed key implementation considerations for optimal use of biomarkers, and identified areas for future research. CONCLUSIONS: In patients with UC, noninvasive biomarkers, including fecal calprotectin, fecal lactoferrin, and serum CRP can inform disease monitoring and management.

Burden, Causes, and Outcomes of Hospitalization in Patients With Giant Cell Arteritis: A US National Cohort Study.

OBJECTIVE: Giant cell arteritis (GCA) has a relapsing-remitting course and is associated with a high burden of comorbidities, leading to repeated hospitalizations. This study was undertaken to investigate the burden, risk factors, causes, and outcomes of hospitalization and readmission in GCA patients in a US national cohort. METHODS: Using the 2017 US National Readmission Database, we identified adults ≥50 years of age hospitalized with GCA between January and June 2017, with at least 6 months of follow-up. We estimated the burden of hospitalization including 6-month risk of readmission, total days spent in hospital, and costs, annually. We examined patient-, hospital-, and index hospitalization-related factors for 6-month readmission and total days of hospitalization using binomial logistic regression. RESULTS: Our study included 1,206 patients hospitalized with GCA (70% women, median age 77 years), with 13% of patients experiencing GCA-related ophthalmologic complications at index hospital admission. On follow-up, 3% died, and 34% of patients were readmitted within 6 months, primarily for infections (23%) and cardiovascular diseases (CVDs) (15%). Charlson comorbidity index (CCI) of ≥1, smoking, and obesity were associated with readmission. GCA patients spent a median of 5 days/year in hospital (interquartile range [IQR] 3-11), with those in the top quartile spending 19 days/year in hospital (IQR 14-26). CONCLUSION: GCA patients frequently experience unplanned health care utilization, with 1 in 3 patients experiencing readmission within 6 months, and 3% dying within the follow-up period. Infection and CVDs are common causes of readmission and may be related to glucocorticoid exposure. Population health management strategies are required in these vulnerable GCA patients.

Gender Related Differences in Surgeon Compensation: Survey Results from the American Society of Colon and Rectal Surgeons.

OBJECTIVE: We sought to understand the effect of sex on compensation among colorectal surgeons and to determine which factors contribute to gender-based differences in compensation. SUMMARY OF BACKGROUND DATA: The sex-based wage gap in the medical profession is among the most pronounced wage gaps in the U.S. Data regarding the wage gap among colorectal surgeons and the underlying reasons for this disparity remain unclear. METHODS: The Healthcare Economics Committee of the American Society of Colon and Rectal Surgeons conducted a survey to evaluate surgeon demographics, compensation, and practice characteristics. To evaluate the effect of sex on compensation, we performed multivariable linear regression with backward selection. We used a two-sided P -value with a significance threshold <0.05. RESULTS: The mean difference in normalized total compensation between men and women was $46,250, and when salary was adjusted for FTEs, the difference was $57,000. Women were more likely to perform anorectal surgery, less likely to perform general surgery and less likely to hold positions in leadership. After adjustments, women reported significantly lower compensation (aOR, 0.88; 95% CI, 0.80-0.97). Time spent doing abdominal surgery (aOR, 1.13; 95% CI 1.03-1.23), professor status (aOR, 1.17; 95% CI, 1.03-1.32) and instructor status (aOR, 1.49; 95% 1.28-1.73) were independently associated with compensation. CONCLUSIONS: We found a 12% adjusted sex wage gap among colorectal surgeons. Gender-based differences in leadership positions and allocation of effort may contribute. Further research will be necessary to clarify sources of wage inequalities. Still, our results should prompt expedient actions to support closing the gap.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Impact of recurrent hospitalization for Clostridioides difficile on longitudinal outcomes in patients with inflammatory bowel diseases: a nationally representative cohort.

Background: Clostridioides difficile infection (CDI) is associated with poor outcomes in patients with inflammatory bowel diseases (IBD). Objectives: We conducted a nationally representative cohort study to evaluate the impact of recurrent CDI (rCDI)-related hospitalization on longitudinal unplanned healthcare utilization in patients with IBD. Design: This was a retrospective cohort study that utilized the 2017 Nationwide Readmissions Database (NRD). Methods: We identified 13,446 patients with IBD, hospitalized at least twice from January to June 2017 and followed through December 2017; of these, 1,148 had CDI-related hospitalizations. We compared the annual burden of hospitalization and IBD-related surgery in IBD patients with rCDI-related admission versus single CDI-related admission (primary reference), and those with one or more CDI-related admission versus no CDI-related admission (secondary reference). Results: There were no significant differences in risk and burden of unplanned healthcare utilization (time spent in-hospital, 27 days versus 27 days, p = 0.62), 6-month readmission (63% versus 64.3%, p = 0.8) or IBD-related surgery in patients with recurrent (two or more) CDI-related hospitalizations versus single CDI-related admission. However, patients with ⩾1 CDI-related admission versus no CDI admissions experienced higher rate of 6-month readmission (61.1% versus 55.7%, p<.001), total days spent in the hospital per year (median: 26 days versus 21 days, p<.001), total cost across all hospitalizations per year ($212,524 versus $184,384, p < 0.01), and inpatient mortality (3.28% versus 1.81%, p = 0.01), without an increase in risk of IBD-related surgery (6.7% versus 6.4%, p = 0.79). Conclusion: While patients with IBD hospitalized for CDI have poor longitudinal inpatient outcomes, recurrent admissions for CDI may not increase risk of adverse outcomes compared to one-time admission.

Simplified Machine Learning Models Can Accurately Identify High-Need High-Cost Patients With Inflammatory Bowel Disease.

INTRODUCTION: Hospitalization is the primary driver of inflammatory bowel disease (IBD)-related healthcare costs and morbidity. Traditional prediction models have poor performance at identifying patients at highest risk of unplanned healthcare utilization. Identification of patients who are high-need and high-cost (HNHC) could reduce unplanned healthcare utilization and healthcare costs. METHODS: We conducted a retrospective cohort study in adult patients hospitalized with IBD using the Nationwide Readmissions Database (model derivation in the 2013 Nationwide Readmission Database and validation in the 2017 Nationwide Readmission Database). We built 2 tree-based algorithms (decision tree classifier and decision tree using gradient boosting framework [XGBoost]) and compared traditional logistic regression to identify patients at risk for becoming HNHC (patients in the highest decile of total days spent in hospital in a calendar year). RESULTS: Of 47,402 adult patients hospitalized with IBD, we identified 4,717 HNHC patients. The decision tree classifier model (length of stay, Charlson Comorbidity Index, procedure, Frailty Risk Score, and age) had a mean area under the receiver operating characteristic curve (AUC) of 0.78 ± 0.01 in the derivation data set and 0.78 ± 0.02 in the validation data set. XGBoost (length of stay, procedure, chronic pain, drug abuse, and diabetic complication) had a mean AUC of 0.79 ± 0.01 and 0.75 ± 0.02 in the derivation and validation data sets, respectively, compared with AUC 0.55 ± 0.01 and 0.56 ± 0.01 with traditional logistic regression (peptic ulcer disease, paresthesia, admission for osteomyelitis, renal failure, and lymphoma) in derivation and validation data sets, respectively. DISCUSSION: In hospitalized patients with IBD, simplified tree-based machine learning algorithms using administrative claims data can accurately predict patients at risk of progressing to HNHC.

Proactive Therapeutic Drug Monitoring Versus Conventional Management for Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Proactive therapeutic drug monitoring (TDM) has been proposed to improve outcomes in patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF)α antagonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing proactive TDM with conventional management in patients with IBD. METHODS: We identified RCTs in patients with IBD treated with TNFα antagonists comparing proactive TDM (routine assessments of trough concentration with dose adjustments to maintain predetermined trough concentration, regardless of disease activity) with conventional management (clinically driven dose adjustments). The primary outcome was failure to maintain clinical remission. Certainty of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: On meta-analysis of 9 RCTs (8 RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709; 38%) vs conventional management (292/696; 42%) (relative risk [RR], 0.96; 95% confidence interval [CI], 0.81-1.13) with moderate heterogeneity (inconsistency index = 36%) (Grading of Recommendations, Assessment, Development and Evaluations; low certainty evidence), with no differences in patients with Crohn's disease (RR, 0.87 ; 95% CI, 0.66-1.15) and ulcerative colitis (RR, 0.88; 95% CI, 0.72-1.07). Disease duration, concomitant immunomodulators, disease activity at baseline, and optimization of therapy before randomization did not modify this association. No differences were observed in risk of developing antidrug antibodies or serious adverse events. Patients in the proactive TDM arm were more likely to undergo dose escalation (RR, 1.56; 95% CI, 1.25-1.94). CONCLUSIONS: Routine proactive TDM to target biologic concentration to specific thresholds, regardless of disease activity, did not offer clinical benefit in patients with IBD treated with TNFα antagonists in RCTs conducted to date. We cannot exclude the possibility of benefit in disease subtypes and phases of therapy (induction) not represented in these RCT populations.

Impact of Comorbid Psychiatric Disorders on Healthcare Utilization in Patients with Inflammatory Bowel Disease: A Nationally Representative Cohort Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) frequently experience comorbid psychiatric disorders, which negatively impact quality of life. We characterized the longitudinal burden of hospitalization-related healthcare utilization in adults with IBD with and without comorbid anxiety, depression, or bipolar disorder. METHODS: In the 2017 Nationwide Readmissions Database (NRD), we identified 40,177 patients with IBD who were hospitalized between January 1, 2017 and June 30, 2017 and who were followed until December 31, 2017. In this cohort, we compared the annual burden (i.e., total days spent in hospital), costs, risk of readmission, inpatient mortality, and IBD-related surgery in patients with and without comorbid psychiatric disorders (anxiety, depression, or bipolar disorder). RESULTS: Of the 40,177 adults who were hospitalized for IBD, 25.7% had comorbid psychiatric disorders. Over a 10 month-long period of follow-up, patients with comorbid psychiatric disorders spent more days in the hospital (median, 7 days vs. 5 days, p < 0.01), experienced higher 30-day (31.3 vs. 25.4%; p < 0.01) and 90-day (42.6 vs. 35.3%, p < 0.01) readmission rates, and had higher hospitalization-related costs (median, $41,418 vs. $39,242, p < 0.01). However, they were less likely to undergo IBD-related procedures or surgeries. There were no differences in risk of mortality. On Cox proportional hazard analysis, the presence of comorbid psychiatric disorders was associated with a 16% higher risk of readmission (HR, 1.16; 95% CI, 1.13-1.20) and a 13% higher risk of severe IBD-related hospitalization (HR, 1.13; 95% CI, 1.08-1.16). CONCLUSIONS: In adults with IBD, comorbid psychiatric disorders were independently associated with a higher burden and cost of hospitalization, without an increase in the risk of IBD-related surgery or procedures. Population-based interventions aimed at treating psychiatric comorbidities may decrease the risk of unplanned healthcare utilization.

Preserved SARS-CoV-2 Vaccine Cell-Mediated Immunogenicity in Patients With Inflammatory Bowel Disease on Immune-Modulating Therapies.

Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications.

Machine Learning-based Prediction Models for Diagnosis and Prognosis in Inflammatory Bowel Diseases: A Systematic Review.

BACKGROUND AND AIMS: There is increasing interest in machine learning-based prediction models in inflammatory bowel diseases [IBD]. We synthesised and critically appraised studies comparing machine learning vs traditional statistical models, using routinely available clinical data for risk prediction in IBD. METHODS: Through a systematic review till January 1, 2021, we identified cohort studies that derived and/or validated machine learning models, based on routinely collected clinical data in patients with IBD, to predict the risk of harbouring or developing adverse clinical outcomes, and reported its predictive performance against a traditional statistical model for the same outcome. We appraised the risk of bias in these studies using the Prediction model Risk of Bias ASsessment [PROBAST] tool. RESULTS: We included 13 studies on machine learning-based prediction models in IBD, encompassing themes of predicting treatment response to biologics and thiopurines and predicting longitudinal disease activity and complications and outcomes in patients with acute severe ulcerative colitis. The most common machine learning models used were tree-based algorithms, which are classification approaches achieved through supervised learning. Machine learning models outperformed traditional statistical models in risk prediction. However, most models were at high risk of bias, and only one was externally validated. CONCLUSIONS: Machine learning-based prediction models based on routinely collected data generally perform better than traditional statistical models in risk prediction in IBD, though frequently have high risk of bias. Future studies examining these approaches are warranted, with special focus on external validation and clinical applicability.

Patient-Reported Outcomes and Risk of Hospitalization and Readmission in Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Patient-reported outcome measures (PROMs) provide a wholesome view of patient well-being. We conducted a retrospective cohort study to evaluate whether PROMs inform risk of unplanned healthcare utilization in patients with IBD. METHODS: We identified adult patients with IBD who completed at least two surveys in a large Internet-based cohort within 1 year. We evaluated the association between baseline patient characteristics, disease activity indices, medication use, and PROMs, assessed using NIH Patient-Reported Outcome Measurement Information System (PROMIS) and subsequent risk of incident hospitalization (at time of first follow-up) within 1 year, and readmission within 1 year (in patients with hospitalization at first follow-up), using multivariable logistic regression. RESULTS: Of 7902 patients with IBD (45.5 year, 72% females, 63% Crohn's disease), 1377 (17.4%) were hospitalized within 1 year. Among PROMs, pain interference (adjusted OR per 5-point increase in PROMIS, 1.09; 95% CI 1.05-1.14), but not depression, anxiety, fatigue or sleep disturbance, was predictive of higher risk of hospitalization. Prior surgery or hospitalization, symptomatic disease, biologic, and corticosteroid use were also associated with higher risk of hospitalization. Of 521 patients hospitalized with IBD, 133 (25.5%) were readmitted within 1 year. Anxiety and pain interference were predictive of higher risk of readmission, whereas depression was associated with lower risk of readmission. CONCLUSIONS: In a large Internet-based cohort study, PROMs may have a modest effect on modifying risk of unplanned healthcare utilization in patients with IBD, with pain interference being most consistently associated with increased risk of hospitalization and readmission.

Systematic Review and Meta-Analysis: Risk of Hospitalization in Patients with Ulcerative Colitis and Crohn's Disease in Population-Based Cohort Studies.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) lead to high morbidity and unplanned healthcare utilization. We conducted a systematic review with meta-analysis to estimate the cumulative incidence of IBD-related (and all-cause) hospitalization in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Through a systematic review to September 3, 2019, we identified population-based inception cohort studies in patients with IBD that reported patient-level cumulative incidence of hospitalization at 1, 3 and 5 years after diagnosis. Hospitalization risk was pooled using random effects meta-analysis, and risk factors analyzed through mixed-effects meta-regression and qualitative synthesis. RESULTS: In patients with UC (6 cohorts), 1-, 3- and 5-year risk of UC-related hospitalization was 10.4% (95% CI 8.2-13.2), 17.0% (95% CI 14.0-20.4) and 21.5% (95% CI 18.0-25.4), respectively, with considerable heterogeneity. In patients with CD (6 cohorts), 1-, 3- and 5-year risk of CD-related hospitalization was 29.3% (95% CI 20.0-40.8), 38.5% (95% CI 26.8-51.7) and 44.3% (95% CI 32.7-56.5), respectively, with considerable heterogeneity. On meta-regression, steady decline in risk of hospitalization was observed in patients diagnosed in a more contemporary era. Younger age at onset (both UC and CD), extensive colitis (UC), ileal-dominant CD, perianal CD and penetrating and/or stricturing behavior (CD) and early need for corticosteroids and immunosuppressive therapy (both UC and CD) were associated with increased risk of hospitalization. CONCLUSION: Approximately one in five and one in two patients with UC and CD are hospitalized within 5 years of diagnosis, respectively. Population health management strategies are required to mitigate unplanned healthcare utilization.

Trends in U.S. Health Care Spending on Inflammatory Bowel Diseases, 1996-2016.

BACKGROUND: Inflammatory bowel diseases (IBD) are rising in prevalence and are associated with high health care costs. We estimated trends in U.S. health care spending in patients with IBD between 1996 and 2016. METHODS: We used data on national health care spending developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. We estimated corresponding U.S. age-specific prevalence of IBD from the Global Burden of Diseases Study. From these 2 sources, we estimated prevalence-adjusted, temporal trends in U.S. health care spending in patients with IBD, stratified by age groups (<20 years, 20-44 years, 45-64 years, ≥65 years) and by type of care (ambulatory, inpatient, emergency department [ED], pharmaceutical prescriptions, and nursing care), using joinpoint regression, expressed as an annual percentage change (APC) with 95% confidence intervals. RESULTS: Overall, annual U.S. health care spending on IBD increased from $6.4 billion (95% confidence interval, 5.7-7.4) in 1996 to $25.4 billion (95% confidence interval, 22.4-28.7) in 2016, corresponding to a per patient increase in annual spending from $5714 to $14,033. Substantial increases in per patient spending on IBD were observed in patients aged ≥45 years. Between 2011 and 2016, inpatient and ED care accounted for 55.8% of total spending and pharmaceuticals accounted for 19.9%, with variation across age groups (inpatient/ED vs pharmaceuticals: ages ≥65 years, 57.6% vs 11.2%; ages 45-64 years, 49.5% vs 26.9%; ages 20-44 years, 59.2% vs 23.6%). CONCLUSIONS: Even after adjusting for rising prevalence, U.S. health care spending on IBD continues to progressively increase, primarily in middle-aged and older adults, with unplanned health care utilization accounting for the majority of costs.

Digital Health Technologies for Remote Monitoring and Management of Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: Digital health technologies may be useful tools in the management of chronic diseases. We performed a systematic review of digital health interventions in the management of patients with inflammatory bowel diseases (IBD) and evaluated its impact on (i) disease activity monitoring, (ii) treatment adherence, (iii) quality of life (QoL) measures, and/or (iv) health care utilization. METHODS: Through a systematic review of multiple databases through August 31, 2020, we identified randomized controlled trials in patients with IBD comparing digital health technologies vs standard of care (SoC) for clinical management and monitoring and reporting impact on IBD disease activity, treatment adherence, QoL, and/or health care utilization or cost-effectiveness. We performed critical qualitative synthesis of the evidence supporting digital health interventions in patients with IBD and rated certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Overall, we included 14 randomized controlled trials (median, 98 patients; range 34-909 patients; follow-up <12 months) that compared web-based interventions, mobile applications, and different telemedicine platforms with SoC (clinic-based encounters). Although overall disease activity and risk of relapse were comparable between digital health technologies and SoC (very low certainty of evidence), digital health interventions were associated with lower rate of health care utilization and health care costs (low certainty of evidence). Digital health interventions did not significantly improve patients' QoL and treatment adherence compared with SoC (very low certainty of evidence). Trials may have intrinsic selection bias due to nature of digital interventions. DISCUSSION: Digital health technologies may be effective in decreasing health care utilization and costs, though may not offer advantage in reducing risk of relapse, QoL, and improving treatment adherence in patients with IBD. These techniques may offer value-based care for population health management.

Abdominal free fluid in acute pancreatitis predicts necrotizing pancreatitis and organ failure.

BACKGROUND: Abdominal free fluid is frequently encountered on cross-sectional imaging for acute pancreatitis and may be a sign of increased severity and complications. This study examines the ability of free fluid to predict necrotizing pancreatitis and other adverse outcomes. METHODS: We conducted a single-center retrospective study of patients with acute pancreatitis and multiple cross-sectional imaging studies. Patients were divided into those who demonstrated free fluid on initial imaging and those without free fluid. The primary outcome was developing necrotizing pancreatitis. Logistic regression analysis assessed the performance of several predictors. RESULTS: A total of 245 acute pancreatitis patients were included. Pancreatic necrosis occurred more frequently in the free fluid group (31.3 vs. 1.3%, P<0.001). The free fluid group also had higher rates of transient organ failure (17.7 vs. 3.4%, P<0.001), persistent organ failure (17.7 vs. 2.0%, P<0.001), in-hospital mortality (7.3 vs. 1.3%, P=0.016), length of stay (16.2 vs. 5.5 days, P<0.001), and intensive care unit admission (30.2 vs. 4.7%, P<0.001). On multivariate logistic regression, free fluid was the strongest predictor (adjusted odds ratio 17.11, 95% confidence interval 3.68-79.65; P<0.001) for necrotizing pancreatitis, with an excellent performance (area under the curve 0.92). When neither fluid on initial imaging nor persistent systemic inflammatory response syndrome was present, the negative predictive value for developing pancreatic necrosis was 100%. CONCLUSIONS: Free fluid in acute pancreatitis is a strong predictor for necrotizing pancreatitis, organ failure and mortality, and outperformed current predictors. Patients who lacked both free fluid on imaging and persistent systemic inflammatory response syndrome are at low risk for adverse outcomes and may be considered for early discharge.

Cost-Related Nonadherence to Medications Among US Adults With Chronic Liver Diseases.

OBJECTIVE: To estimate the prevalence, risk factors, and consequences of cost-related medication nonadherence (CRN) in individuals with chronic liver diseases (CLDs) in the United States. PATIENTS AND METHODS: Using the National Health Interview Survey from January 1, 2014, to December 31, 2018, we identified individuals with CLDs. Using complex weighted survey analysis, we obtained national estimates and risk factors for CRN and its association with cost-reducing behaviors and measures of financial toxicity. We evaluated the association of CRN with unplanned health care use, adjusting for age, sex, race/ethnicity, insurance, income, education, and comorbid conditions. RESULTS: Of 3237 respondents (representing 4.6 million) US adults with CLDs, 813 (representing 1.2 million adults, or 25%; 95% CI, 23% to 27%) reported CRN, of whom 68% (n=554/813) reported maladaptive cost-reducing behaviors. Younger age, female sex, low income, and multimorbidity were associated with a higher prevalence of CRN. Compared with patients without CRN, patients experiencing CRN had 5.1 times higher odds of financial hardship from medical bills (adjusted odds ratio [aOR], 5.05; 95% CI, 3.73 to 6.83) and 2.9 times higher odds of food insecurity (aOR, 2.85; 95% CI, 2.02 to 4.01). The CRN was also associated with 1.5 times higher odds of emergency department visits (aOR, 1.46; 95% CI, 1.11 to 1.94). CONCLUSION: We observed a high prevalence of CRN and associated consequences such as high financial distress, financial hardship from medical bills, food insecurity, engagement in maladaptive cost-reducing strategies, increased health care use, and work absenteeism among patients with CLD. These financial determinants of health have important implications in the context of value-based care.

Trends in the Economic Burden of Chronic Liver Diseases and Cirrhosis in the United States: 1996-2016.

INTRODUCTION: The management of chronic liver diseases (CLDs) and cirrhosis is associated with substantial healthcare costs. We aimed to estimate trends in national healthcare spending for patients with CLDs or cirrhosis between 1996 and 2016 in the United States. METHODS: National-level healthcare expenditure data developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project and prevalence of CLDs and cirrhosis derived from the Global Burden of Diseases Study were used to estimate temporal trends in inflation-adjusted US healthcare spending, stratified by setting of care (ambulatory, inpatient, emergency department, and nursing care). Joinpoint regression was used to evaluate temporal trends, expressed as annual percent change (APC) with 95% confidence intervals (CIs). Drivers of change in spending for ambulatory and inpatient services were also evaluated. RESULTS: Total expenditures in 2016 were $32.5 billion (95% CI, $27.0-$40.4 billion). Over 65% of spending was for inpatient or emergency department care. From 1996 to 2016, there was a 4.3%/year (95% CI, 2.8%-5.8%) increase in overall healthcare spending for patients with CLDs or cirrhosis, driven by a 17.8%/year (95% CI, 14.5%-21.6%) increase in price and intensity of hospital-based services. Total healthcare spending per patient with CLDs or cirrhosis began decreasing after 2008 (APC -1.7% [95% CI, -2.1% to -1.2%]), primarily because of reductions in ambulatory care spending (APC -9.1% [95% CI, -10.7% to -7.5%] after 2011). DISCUSSION: Healthcare expenditures for CLDs or cirrhosis are substantial in the United States, driven disproportionately by acute care in-hospital spending.