Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease.

Background: Serum protein reflects albumin and globulin levels, both of which can be altered in inflammatory bowel disease (IBD). The implications of a high globulin fraction in IBD are unknown. We hypothesized that a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period. Methods: This was an observational study from a prospective IBD registry of a tertiary care center. High globulin fraction was defined as an elevated globulin level >4 g/dL. Data collected included patient demographics, medication exposures, quality-of-life scores, disease activity, emergency department visits, telephone calls, hospitalizations, and IBD-related surgeries over a 4-year period. Comparisons between patients with a high globulin fraction and those without were performed using Pearson's chi-squared, Student's and Mann-Whitney tests. Multivariate analyses were used to assess the relationship between high globulin fraction and healthcare utilization. Results: A total of 1767 IBD patients with a 4-year follow up were included: 53.5% female, mean age 48.4±15.1 years, and 65.4% with Crohn's disease. Of these patients, 446 (25.2%) presented with elevated globulin fraction. Patients with a high globulin fraction were more likely to be hospitalized during the study period. This result remained significant after multivariate analysis for both Crohn's disease patients and those with ulcerative colitis. Conclusion: A high globulin fraction is independently associated with greater disease severity and healthcare utilization in IBD patients, and may function as a routinely available biomarker of a more severe future disease trajectory.

Accuracy of Skin Cancer Diagnosis by Physician Assistants Compared With Dermatologists in a Large Health Care System.

Importance: Physician assistants (PAs) are increasingly used in dermatology practices to diagnose skin cancers, although, to date, their diagnostic accuracy compared with board-certified dermatologists has not been well studied. Objective: To compare diagnostic accuracy for skin cancer of PAs with that of dermatologists. Design, Setting, and Participants: Medical record review of 33 647 skin cancer screening examinations in 20 270 unique patients who underwent screening at University of Pittsburgh Medical Center-affiliated dermatology offices from January 1, 2011, to December 31, 2015. International Classification of Diseases, Ninth Revision code V76.43 and International Classification of Diseases and Related Health Problems, Tenth Revision code Z12.83 were used to identify pathology reports from skin cancer screening examinations by dermatologists and PAs. Exposure: Examination performed by a PA or dermatologist. Main Outcomes and Measures: Number needed to biopsy (NNB) to diagnose skin cancer (nonmelanoma, invasive melanoma, or in situ melanoma). Results: Of 20 270 unique patients, 12 722 (62.8%) were female, mean (SD) age at the first visit was 52.7 (17.4) years, and 19 515 patients (96.3%) self-reported their race/ethnicity as non-Hispanic white. To diagnose 1 case of skin cancer, the NNB was 3.9 for PAs and 3.3 for dermatologists (P < .001). Per diagnosed melanoma, the NNB was 39.4 for PAs and 25.4 for dermatologists (P = .007). Patients screened by a PA were significantly less likely than those screened by a dermatologist to be diagnosed with melanoma in situ (1.1% vs 1.8% of visits, P = .02), but differences were not significant for invasive melanoma (0.7% vs 0.8% of visits, P = .83) or nonmelanoma skin cancer (6.1% vs 6.1% of visits, P = .98). Conclusions and Relevance: Compared with dermatologists, PAs performed more skin biopsies per case of skin cancer diagnosed and diagnosed fewer melanomas in situ, suggesting that the diagnostic accuracy of PAs may be lower than that of dermatologists. Although the availability of PAs may help increase access to care and reduce waiting times for appointments, these findings have important implications for the training, appropriate scope of practice, and supervision of PAs and other nonphysician practitioners in dermatology.

Ileocecal Anastomosis Type Significantly Influences Long-Term Functional Status, Quality of Life, and Healthcare Utilization in Postoperative Crohn's Disease Patients Independent of Inflammation Recurrence.

OBJECTIVES: Anastomotic reconstruction following intestinal resection in Crohn's disease (CD) may employ side-to-side anastomosis (STSA; anti-peristaltic orientation) or end-to-end anastomosis (ETEA). Our aim was to determine the impact of these two anastomotic techniques on long-term clinical status in postoperative CD patients. METHODS: We performed a comparative effectiveness study of prospectively collected observational data from consented CD patients undergoing their first or second ileocolonic bowel resection and re-anastomosis between 2008 and 2012, in order to assess the association between anastomosis type and 2-year postoperative quality of life (QoL), healthcare utilization, disease clinical or endoscopic recurrence, use of medications, and need for repeat resection. RESULTS: One hundred and twenty eight postoperative CD patients (60 STSA and 68 ETEA) were evaluated. At 2 years postoperatively, STSA patients had higher rates of emergency department visits (33.3% vs. 14.7%; P=0.01), hospitalizations (30% vs. 11.8%; P=0.01), and abdominal computed tomography scans (50% vs. 13.2%; P<0.001) with lower QoL (mean short inflammatory bowel disease questionnaire 47.9 vs. 53.4; P=0.007). There was no difference among the two groups in the 30 day surgical complications and 2-year patterns of disease activity, CD medication requirement, endoscopic recurrence, and need for new surgical management (all P > 0.05). CONCLUSIONS: At 2 years postoperatively, CD patients with ETEA demonstrated better QoL and less healthcare utilization compared with STSA, despite having similar patterns of disease recurrence and CD treatment. These findings suggest that surgical reconstruction of the bowel as an intact tube (ETEA) contribute to improved functional and clinical status in patients with CD.

Telephone Encounters Predict Future High Financial Expenditures in Inflammatory Bowel Disease Patients: A 3-Year Prospective Observational Study.

BACKGROUND: Telephone activity is essential in management of complex chronic diseases including inflammatory bowel disease (IBD). Telephone encounters logged in the electronic medical record have recently been proposed as a surrogate marker of disease activity and impending health care utilization; however, the association between telephone calls and financial expenditures has not been evaluated. STUDY: We performed a 3-year prospective observational study of telephone encounters logged at a tertiary referral IBD center. We analyzed patient demographics, disease characteristics, comorbidities, clinical activity, and health care financial charges by telephone encounter frequency. RESULTS: Eight hundred one patients met inclusion criteria (52.3% female; mean age, 44.1 y), accounted for 12,669 telephone encounters, and accrued $70,513,449 in charges over 3 years. High telephone encounter frequency was associated with female gender (P=0.003), anxiety/depression (P<0.001), and prior IBD surgery (P<0.001). High telephone encounter categories had significantly more hospitalizations (P<0.001), IBD surgery (P<0.001), worse quality of life (P<0.001), more corticosteroid (P<0.001), biological (P<0.001), and opiate prescriptions (P<0.001). High telephone encounter frequency patients amassed higher total available charges in each year (P<0.001) and over the 3 years (P<0.001). Telephone encounters in 2009 (P=0.02) and 2010 (P<0.001) were significantly associated with financial charges the following year after controlling for demographic, utilization, and medication covariates. CONCLUSIONS: Increased telephone encounters are associated with significantly higher health care utilization and financial expenditures. Increased call frequency is predictive of future health care spending. Telephone encounters are a useful tool to identify patients at risk of clinical deterioration and large financial expense.

Peripheral Eosinophilia in Patients With Inflammatory Bowel Disease Defines an Aggressive Disease Phenotype.

OBJECTIVES: Peripheral blood eosinophilia (PBE) in inflammatory bowel disease (IBD) is associated with ulcerative colitis (UC) and active disease. Little data exist on the long-term impact of PBE on disease course. We aimed to investigate the multi-year patterns of PBE and its impact on disease severity in a large IBD cohort. METHODS: We performed a registry analysis of a consented, prospective, natural history IBD cohort at a tertiary center from 2009 to 2014. Demographics, comorbidities, disease activity, healthcare utilization, and time to hospitalization or surgical resection of patients who displayed PBE were compared to patients without PBE. RESULTS: Of the 2,066 IBD patients, 19.2% developed PBE. PBE was significantly associated with UC (P<0.001), extensive colitis (P<0.001), and shorter disease duration (P=0.03). Over six years, PBE patients had more active disease (Harvey-Bradshaw Index P=0.001; ulcerative colitis activity index P<0.001), concurrent C-reactive protein elevation (P<0.001), healthcare utilization (hospitalization P<0.001, IBD surgery P<0.001), and more aggressive medical therapy (prednisone P<0.001, anti-TNF P<0.001). Patients with PBE had a significantly reduced time to hospitalization in both UC (P<0.001) and Crohn's disease (CD) (P<0.001) and reduced time to colectomy in UC (P=0.003). On multivariable modeling, PBE remained significantly associated with hospitalization and surgery in both CD and UC. New diagnosis of UC with PBE was associated with increased steroid (P=0.007) and anti-TNF (P=0.001) requirement. CONCLUSION: This multi-year study of a large IBD cohort suggests that peripheral blood eosinophilia represents a biomarker of a distinct IBD subgroup, with a unique inflammatory signature, and at risk for worse clinical outcomes.

Group-Based Trajectory Modeling of Healthcare Financial Charges in Inflammatory Bowel Disease: A Comprehensive Phenotype.

OBJECTIVES: Inflammatory bowel disease (IBD) is a heterogeneous group of chronic inflammatory gastrointestinal conditions with variable disease courses often requiring significant healthcare expenditures. We aimed to identify disease trajectory patterns based on longitudinal financial expenditures and to assess the association of classic disease activity parameters with financial charges. METHODS: This was an analysis of a consented, prospective, natural history IBD registry (2009-2013) from a tertiary IBD center of 2,203 patients and their associated medical charges excluding pharmacy expenses. We applied group-based trajectory modeling to longitudinal healthcare financial charges to determine patterns of charges. We assessed the association between charge patterns and disease activity, quality of life, healthcare utilization, and medication requirement. RESULTS: The final model included 1,600 IBD patients with 5-year charges. We identified six distinct trajectories over the study period. Consistently High charges were associated with Crohn's disease (66.0% Consistently High patients, P<0.01), perianal involvement (22.6%, P<0.01), ulcerative colitis extent (89.7% extensive, P=0.01), prior IBD surgery (52.5%, P<0.01), and depression/anxiety (36.2%, P<0.01). Compared with other trajectories, Consistently High charges had higher 5-year disease activity indices (Harvey-Bradshaw P<0.01; ulcerative colitis activity index P<0.01), elevated C-reactive protein rates (72.3%, P<0.01), IBD surgery (64.5%, P<0.01), hospitalization (97.2%, P<0.01), corticosteroid (70.9%, P<0.01) and antitumor necrosis factor requirement (50.4%, P<0.01), and worse quality of life (P<0.01). Annual trends in parameters were reflected in temporal changes in financial charges. The majority of financial burden stemmed from inpatient care. CONCLUSIONS: Healthcare financial charges represent a novel phenotype in IBD that reflect trends in classic disease activity parameters and allow for subgroup identification of temporal disease trajectories.

Demographic and Clinical Predictors of High Healthcare Use in Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory condition requiring significant healthcare expenditure. Subgroups of individuals contribute disproportionately to spending. We aimed to determine demographic and clinical factors predictive of high healthcare expenditures for IBD patients followed over a multiyear period. METHODS: This was a registry analysis using a prospective observational, consented, natural history registry from a tertiary IBD center and associated medical charges, not including pharmacy expenses. The 100 patients with the highest medical charges (top 5%) were compared with the median 300 patients. Logistic regression determined demographic and clinical factors associated with high charge patients. RESULTS: IBD patients in the high charge group had significantly more unemployment (P < 0.0001), were of black race (P = 0.013), comorbid psychiatric illness (P = 0.002), hypertension (P = 0.01), diabetes (P = 0.004), opiate use (P < 0.0001), perianal involvement (P = 0.002), penetrating disease (P < 0.0001), and extensive colitis (P = 0.01). In multivariate analysis, unemployment (Crohn's disease [CD]: odds ratio [OR], 3.04; 95% confidence interval [CI], 1.32-7.02; ulcerative colitis [UC]: OR, 2.68; 95% CI, 1.20-5.99), psychiatric illness (UC: OR, 2.08; 95% CI, 1.03-4.19), opiates (CD: OR, 5.61; 95% CI, 2.67-11.82; UC: OR, 5.14; 95% CI, 2.52-10.48), prior surgery (CD: OR, 3.29; 95% CI, 1.59-6.82; UC: OR, 2.72; 95% CI, 1.39-5.32), penetrating CD (OR, 3.29; 95% CI, 1.02-10.62), and corticosteroid requirement (CD: OR, 3.78; 95% CI, 1.86-7.65; UC: OR, 2.98; 95% CI, 1.51-5.90) remained independently associated with high charges. CONCLUSIONS: High expenditure IBD patients were affected by more severe disease. The high prevalence of depression, anxiety, and chronic pain in these patients suggests the need for focused treatment of these comorbidities ultimately to reduce financial burden.

Silent Crohn's Disease: Asymptomatic Patients with Elevated C-reactive Protein Are at Risk for Subsequent Hospitalization.

BACKGROUND: Patient-reported Crohn's disease (CD) symptoms and endoscopic evaluation have historically guided routine care, but the risk of complications in asymptomatic patients with elevated C-reactive protein (CRP) is unknown. METHODS: We conducted a prospective observational cohort study of patients with CD from a tertiary care center. Subjects with short inflammatory bowel disease questionnaire scores ≥ 50, Harvey-Bradshaw CD scores ≤ 4, and same-day CRP measurement were eligible for inclusion. The primary outcome was disease-related hospitalization up to 24 months after the qualifying clinic visit. We assessed the relationship between CRP elevation and subsequent hospitalization. RESULTS: There were 351 asymptomatic patients with CD (median age 40 yr; 50.4% female) who met inclusion criteria, and CRP was elevated in 19.7% of these individuals (n = 69). At 24 months, 16.8% (n = 59) of the study population had been hospitalized for CD-related complications. Significantly, more patients with an elevated CRP were hospitalized (33.3% versus 12.8%, P < 0.0001) compared with those with a normal CRP and were hospitalized at increased rate (P < 0.001) on Kaplan-Meier analysis. CRP elevation was significantly and independently associated with increased risk of hospitalization (adjusted hazard ratio 2.12; 95% confidence interval, 1.13-3.98; P = 0.02) in multivariable survival analysis. CONCLUSIONS: Asymptomatic patients with CD with elevated CRP are at a nearly 2-fold higher risk for hospitalization over the subsequent 2 years compared with asymptomatic patients with CD without CRP elevation.