The Cost of Inflammatory Bowel Disease: An Initiative From the Crohn's & Colitis Foundation.

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

Quality of Sleep and Coexistent Psychopathology Have Significant Impact on Fatigue Burden in Patients With Inflammatory Bowel Disease.

BACKGROUND: Fatigue is common in inflammatory bowel disease (IBD) patients and is associated with factors such as psychopathology, sleep quality, and disease activity. GOAL: To investigate the combined role of all the above factors in the burden of fatigue among IBD patients. STUDY: We conducted an observational study of adult patients enrolled in an IBD clinical research registry at a tertiary care clinic. Fatigue burden was defined by Item 1 of the Short-form IBD Questionnaire (SIBDQ), which is scored on a 7-point Likert scale. Crohn's disease (CD) and ulcerative colitis (UC) disease activity were measured with the Harvey-Bradshaw Index or the UC Activity Index, respectively. Labs were obtained to assess anemia, vitamin deficiencies, and inflammatory markers. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Use of psychotropic medications and narcotics was used as proxy measure of psychopathology and pain. RESULTS: Among 685 IBD patients enrolled in the registry, 631 (238 UC, 393 CD) had a complete SIBDQ. High fatigue burden was found in 57.5% of patients (64.4% CD, 46.2% UC). Fatigue burden was significantly associated with sleep disturbance (PSQI), SIBDQ, and disease activity. CD patients had more fatigue burden than UC patients. Multivariate regression showed that poor quality of life, sleep disturbance, and being on a psychotropic medication are significantly associated with fatigue burden for both UC and CD. CONCLUSION: Because fatigue is common in IBD patients, these findings suggest that attention to quality of sleep and psychopathology is as important as medical disease management.

Chronic Pancreatitis in the 21st Century - Research Challenges and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in chronic pancreatitis (CP) and its sequelae. This conference marked the 20th year anniversary of the discovery of the cationic trypsinogen (PRSS1) gene mutation for hereditary pancreatitis. The event was held on July 27, 2016, and structured into 4 sessions: (1) pathophysiology, (2) exocrine complications, (3) endocrine complications, and (4) pain. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to design better tools to diagnose CP and its sequelae early and reliably, identify predisposing risk factors for disease progression, develop standardized protocols to distinguish type 3c diabetes mellitus from other types of diabetes, and design effective therapeutic strategies through novel cell culture technologies, animal models mimicking human disease, and pain management tools. Gene therapy and cystic fibrosis conductance regulator potentiators as possible treatments of CP were discussed. Importantly, the need for CP end points and intermediate targets for future drug trials was emphasized.

Inflammatory Bowel Disease (IBD) Connect: A Novel Volunteer Program for Hospitalized Patients with IBD and Their Families.

Patients with inflammatory Bowel Disease (IBD) often require hospitalization and this experience is stressful. Health care providers frequently do not have adequate time to address the emotional impact of the hospitalization on the patient and family. Nonmedical support for inpatients was identified as an unmet need by a Crohn's disease patient's family. This led to the development of a volunteer peer specialist network, IBD Connect, where peer volunteers visit hospitalized patients with IBD to offer emotional support and educational materials. We aimed to determine the feasibility of incorporating IBD Connect into an inpatient IBD service, evaluate the impact of IBD Connect on patients' willingness to share their disease experience with family and friends, and improve stress. Since the inception of IBD Connect in 2012, peer volunteers have made 1469 total visits to 677 unique inpatients. Patient satisfaction of IBD Connect has been favorable with a significant decrease in stress related to the hospitalization. Similarly, there was significant increase in patients sharing their IBD diagnosis and experience with family and friends. Patients and their families are willing to share important information and ask questions to volunteers that may not have been discussed with their health care providers. In an era of patient-reported outcomes and patient-centered care, peer volunteers are an important component of chronic disease management and should be incorporated into IBD inpatient health care teams.

Effect of Psychotherapy on Health Care Utilization in Children With Inflammatory Bowel Disease and Depression.

OBJECTIVES: Pediatric patients with inflammatory bowel disease (IBD) are at an increased risk of developing depression compared with community controls. Depression often negatively influences illness behaviors such as resource utilization. We sought to investigate the effects of treating depression on utilization of medical resources in depressed pediatric patients with IBD by comparing rates of health care utilization 1 year before and after psychotherapy. METHOD: Two hundred seventeen subjects ages 9 to 17 years with IBD and depression received 3 months of psychotherapy for depression as part of a multicenter randomized controlled trial. Of these 217 subjects, 70 had utilization data available 1 year prior and 1 year after receiving 3 months of psychotherapy. Primary outcomes included frequency of hospitalizations, inpatient hospital days, outpatient gastrointestinal visits, and number of emergency room visits, radiological examinations, and endoscopies. Within subject analyses were completed comparing health care utilization 12 months before psychotherapy compared with the 12 months after the conclusion of psychotherapy. RESULTS: Fifty-one and 19 patients had CD and UC, respectively. A total of 55.7% of patients had major depression and 44.3% had minor depression. Overall, all study measures of health care utilization were significantly reduced after psychotherapy (P < 0.01)-including gastrointestinal-related (mean values) hospitalization frequency, inpatient days, outpatient visit, emergency room visits, radiological examinations, and endoscopies. CONCLUSIONS: Psychotherapy for comorbid depression in pediatric patients with IBD is associated with decreased GI-related health care utilization. The present study highlights the importance of screening for depression in a pediatric population with IBD, and that psychotherapy may be a reasonable adjunctive treatment for pediatric patients with IBD and comorbid depression.

Inflammatory markers and the pathogenesis of pediatric depression and suicide: a systematic review of the literature.

OBJECTIVE: To evaluate the relationship and identify support for pathways linking inflammatory processes with depression and suicide in children and adolescents. DATA SOURCES: We designed and implemented comprehensive literature searches in MEDLINE, PsycINFO, and EMBASE. We searched the databases with database-specific controlled vocabulary in conjunction with keywords (eg, inflammation, interleukin, cytokine, C-reactive protein, depression, suicide) in various combinations for reports published in English through May 2013. STUDY SELECTION: The searches identified a total of 1,543 citations, of which 55 were selected for further review and ultimately 27 were identified for inclusion. Studies were selected using 2 criteria. The first criterion required that studies include a biological measure of inflammatory markers in childhood or adolescence. The second criterion required that the studies include a measure of depression or suicide in childhood or adolescence. Articles selected for the review were based on the use of standardized experimental procedures and validated assessment measures. DATA EXTRACTION: All articles were assessed by 2 authors, which ensured that the inclusion criteria were met. Studies were reviewed for association of inflammatory markers with depression and/or suicide. Extracted data included authors, year of publication, study design, population characteristics, inflammatory markers, and depression/suicide measures. Significant and nonsignificant findings were tabulated. RESULTS: The majority of studies were on depression; 2 studies were on suicide, and 7 studies were on inflammatory medical conditions. Most of the participants were adolescents. Interleukin (IL)-1α, IL-1ß, IL-1 receptor antagonist, IL-2, soluble IL-2 receptors, IL-4, IL-6, IL-10, interferon-γ, tumor necrosis factor-α, C-reactive protein, erythrocyte sedimentation rate, and inflammatory cells were assayed across the studies. There was extensive variation in depression measures. Five of the 9 cross-sectional and 3 of the 7 longitudinal studies on depression found a positive association between inflammation and depression. In 3 studies evaluating depression and early adversity, inflammation was more significantly related to adversity than depression was. Results from studies of medical conditions involving inflammation and depression were mixed. CONCLUSIONS: The extant literature provides sufficient data to support a link between inflammatory processes and pediatric depression. However, the directionality of the associations and pathways between the 2 conditions remains to be elucidated. At present, there is insufficient evidence to support the relationship between inflammation and suicidality in youth. Studies on inflammatory medical conditions are warranted in order to understand biological pathways linking inflammation and depression.

Abdominal pain and the neurotrophic system in ulcerative colitis.

BACKGROUND: We undertook a study to test the hypothesis that inflammation alters peripheral sensory mechanisms, thereby contributing to chronic abdominal pain in ulcerative colitis (UC). METHODS: Patients with UC and healthy individuals rated abdominal pain using a visual analog scale and completed surveys describing anxiety or depression (Hospital Anxiety and Depression Score) and gastrointestinal symptoms (Rome III questionnaire). Patient age, sex, and severity of inflammation were determined. Rectal biopsies were processed using immunohistochemical techniques to assess nerve fiber density and real-time PCR to determine transcript expression of neurotrophins (nerve growth factor, glial cell-derived neurotrophic factor, artemin, neurturin), ion channels (transient receptor potential vanilloid type 1, transient receptor potential ankyrin 1) and inflammatory mediators (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-10, IL-17). RESULTS: A total of 77 patients with UC (27 female, 50 male) and 21 controls (10 female, 11 male) were enrolled. Patients with UC with pain had significantly higher depression scores than controls and patients with UC without pain (P < 0.05). There was no correlation between any of the inflammatory markers and pain scores. Visual analog scale pain scores significantly correlated with younger age, higher depression scores, increased expression of neurturin and decreased expression of transient receptor potential ankyrin 1 in the mucosa. Mucosal nerve fiber density did not correlate with any measures of inflammation or pain. Only higher depression scores independently predicted pain in UC (r > 0.5). CONCLUSIONS: We did not observe changes in mucosal innervation and did not see a significant relationship between nerve fiber density, inflammatory mediators, neurotrophic factors, or mucosal ion channel expression and pain. In contrast, the importance of depression as the only independent predictor of pain ratings mirrors functional disorders, where central processes significantly contribute to symptom development and/or perpetuation.

Predictors of abdominal pain in depressed pediatric inflammatory bowel disease patients.

BACKGROUND: Pediatric patients with inflammatory bowel disease (IBD) have high rates of abdominal pain. The study aims were to (1) evaluate biological and psychological correlates of abdominal pain in depressed youth with IBD and (2) determine predictors of abdominal pain in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seven hundred sixty-five patients aged 9 to 17 years with IBD seen over 3 years at 2 sites were screened for depression. Depressed youth completed comprehensive assessments for abdominal pain, psychological (depression and anxiety), and biological (IBD-related, through disease activity indices and laboratory values) realms. RESULTS: Two hundred seventeen patients with IBD (161 CD, 56 UC) were depressed. One hundred sixty-three (120 CD, 43 UC) patients had complete abdominal pain index scores. In CD, abdominal pain was associated with depression (r = 0.33; P < 0.001), diarrhea (r = 0.34; P = 0.001), erythrocyte sedimentation rate (r = 0.22; P = 0.02), low albumin (r = 0.24; P = 0.01), weight loss (r = 0.33; P = 0.001), and abdominal tenderness (r = 0.38, P = 0.002). A multivariate model with these significant correlates represented 32% of the variance in pain. Only depression (P = 0.03), weight loss (P = 0.04), and abdominal tenderness (P = 0.01) predicted pain for patients with CD. In UC, pain was associated with depression (r = 0.46; P = 0.002) and nocturnal stools (r = 0.32; P = 0.046). In the multivariate model with these significant correlates, 23% of the variance was explained and only depression (P = 0.02) predicted pain. CONCLUSIONS: The psychological state of pediatric patients with IBD may increase the sensitivity to abdominal pain. Thus, screening for and treating comorbid depression may prevent excessive medical testing and unnecessary escalation of IBD medications.

Predictors of depression in youth with Crohn disease.

OBJECTIVE: The aim of the study was to determine whether infliximab use and other potential predictors are associated with decreased prevalence and severity of depression in pediatric patients with Crohn disease (CD). METHODS: A total of 550 (n = 550) youth ages 9 to 17 years with biopsy-confirmed CD were consecutively recruited as part of a multicenter randomized controlled trial. Out of the 550, 499 patients met study criteria and were included in the analysis. At recruitment, each subject and a parent completed the Children's Depression Inventory (CDI). A child or parent CDI score ≥  12 was used to denote clinically significant depressive symptoms (CSDS). Child and parent CDI scores were summed to form total CDI (CDIT). Infliximab use, demographic information, steroid use, laboratory values, and Pediatric Crohn's Disease Activity Index (PCDAI) were collected as the potential predictors of depression. Univariate regression models were constructed to determine the relations among predictors, CSDS, and CDIT. Stepwise multivariate regression models were constructed to predict the relation between infliximab use and depression while controlling for other predictors of depression. RESULTS: Infliximab use was not associated with a decreased proportion of CSDS and CDIT after adjusting for multiple comparisons. CSDS and CDIT were positively associated with PCDAI, erythrocyte sedimentation rate, and steroid dose (P < 0.01) and negatively associated with socioeconomic status (SES) (P < 0.001). In multivariate models, PCDAI and SES were the strongest predictors of depression. CONCLUSIONS: Disease activity and SES are significant predictors of depression in youth with Crohn disease.

Characterization of relations among sleep, inflammation, and psychiatric dysfunction in depressed youth with Crohn disease.

OBJECTIVES: Recent reports demonstrate a link between inflammatory bowel disease (IBD) and sleep disturbance. Increased psychiatric dysfunction is consistently reported in patients with IBD. Our objective is to examine relations among sleep disturbance, inflammation, and psychiatric dysfunction in a pediatric population with Crohn disease (CD) and depression. METHODS: Pediatric patients with CD with depression (n = 96) and healthy controls (n = 19) completed measures of sleep (Pittsburgh Sleep Quality Index [PSQI]), depression, anxiety, and abdominal pain, and provided blood for inflammatory markers. CD activity was determined by the Pediatric Crohn's Disease Activity Index. Factor analysis was performed on subscales of the PSQI to derive measures of sleep disturbance. Univariate and multivariate regression analyses assessed relations between sleep disturbance, psychosocial, and biological measures of CD and psychiatric dysfunction. RESULTS: Sleep disturbance in depressed youth with CD was significantly greater than healthy controls, and was significantly related to measures of abdominal pain, depression, and anxiety, but not biomarkers of inflammation. Factor analysis of the PSQI demonstrated a 2-factor solution. The first factor, termed "Qualitative," included Subjective Sleep Quality, Daytime Dysfunction, Sleep Disturbance, and Sleep Latency, whereas the second factor, "Quantitative," consisted of Habitual Sleep Efficiency and Sleep Duration. This factor showed a significant relation to inflammatory markers. Multivariate modeling suggested that qualitative sleep disturbance was predicted by disease activity, pain, and anxiety, whereas quantitative sleep disturbance was predicted by disease activity. CONCLUSIONS: These results indicate that sleep disturbance in depressed youth with CD differs depending upon illness activity. Patients may require different interventions depending upon the sleep disturbance exhibited.

What do changes in inflammatory bowel disease management mean for our patients?

Treatment goals in Crohn's disease are evolving beyond the control of symptoms. A treat-to-target approach to management that features earlier initiation of TNF antagonist therapy will enable resolution of objective parameters of inflammation. The decision to initiate anti-TNF therapy should be based on a patient-specific assessment of risks and benefits. This paradigm necessitates a complex process, influenced by multiple factors that include the quality of data available, physicians' and patients' knowledge of the data, and the preferences and values of patients, physicians and society. The potential 'opportunity cost' resulting from a delay in initiation of effective therapy, a consideration that has been neglected in the past, must also enter into the equation. Our evolving approach to the management of Crohn's disease challenges patients to participate in the decision-making process and to become an active partner in their care. Ideally, this evolution should occur within the context of an enduring physician/patient relationship that is based on mutual trust. Motivational communication provides a useful technique to improve dialogue and collaboration between healthcare professionals and patients, and may help to engage and motivate patients to commit to managing their disease.

Cognitive-behavioral therapy for physical and emotional disturbances in adolescents with polycystic ovary syndrome: a pilot study.

OBJECTIVE: To evaluate the feasibility and effectiveness of an enhanced cognitive-behavioral therapy (CBT), Primary and Secondary Control Enhancement Training (PASCET-PI-2), for physical (obesity) and emotional (depression) disturbances in adolescents with polycystic ovary syndrome (PCOS). METHOD: In an open trial, 12 adolescents with PCOS, obesity, and depression underwent eight weekly sessions and three family-based sessions of CBT enhanced by lifestyle goals (nutrition and exercise), physical illness narrative (meaning of having PCOS), and family psychoeducation (family functioning). RESULTS: Weight showed a significant decrease across the eight sessions from an average of 104 kg (SD = 26) to an average of 93 kg (SD = 18), t(11) = 6.6, p <.05. Depressive symptoms on the Children's Depression Inventory significantly decreased from a mean of 17 (SD = 3) to a mean of 9.6 (SD = 2), t(11) = 16.8, p <.01. CONCLUSION: A manual-based CBT approach to treat depression in adolescents with PCOS and obesity appears to be promising.