Utilization of Treat-to-Target Monitoring Colonoscopy After Treatment Initiation in the US-Based Study of a Prospective Adult Research Cohort With Inflammatory Bowel Disease.

INTRODUCTION: Endoscopic healing has been associated with improved long-term clinical outcomes in inflammatory bowel disease (IBD) and is a recommended target for treatment. Evidence is limited regarding real-world uptake and patterns of treat-to-target monitoring to assess endoscopic healing after treatment initiation. We aimed to estimate the proportion of patients in the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) who received colonoscopy in the 3-15 months after starting a new IBD treatment. METHODS: We identified SPARC IBD patients who initiated a new biologic (infliximab, adalimumab, certolizumab pegol, golimumab, vedolizumab, and ustekinumab) or tofacitinib. We estimated the proportion of patients who received colonoscopies in the 3-15 months after IBD treatment initiation and described use by patient subgroups. RESULTS: Among 1,708 eligible initiations from 2017 to 2022, the most common medications were ustekinumab (32%), infliximab (22%), vedolizumab (20%), and adalimumab (16%). The median patient age was 38 years, with 66% Crohn's disease; 55% were female, and 12% were non-White. In the 3-15 months after medication initiation, 49.3% (95% confidence interval 46.2%-52.5%) of initiations were followed by a colonoscopy. Colonoscopy use was similar between ulcerative colitis and Crohn's disease, but was higher among male patients, those older than 40 years, and those who received colonoscopy within 3 months of initiation. Colonoscopy use varied between study sites, from 26.6% (15.0%-38.3%) to 63.2% (54.5%-72.0%). DISCUSSION: Approximately half of SPARC IBD patients received colonoscopy in the 3-15 months after initiation to a new IBD treatment, suggesting a low uptake of treat-to-target colonoscopy for the assessment of mucosal healing in real-world clinical practice. The variation in colonoscopy use between study sites suggests a lack of consensus and a need for more robust evidence around whether or not the practice of routine monitoring colonoscopy is associated with improved patient outcomes.

Utilization of Colonoscopy Following Treatment Initiation in U.S. Commercially Insured Patients With Inflammatory Bowel Disease, 2013-2019.

BACKGROUND: Evaluation of mucosal healing with colonoscopy is recommended for inflammatory bowel disease (IBD) management; however, little is known about real-world use of treat-to-target monitoring following IBD treatment initiation. We aimed to estimate the proportion of U.S. commercially insured IBD patients who receive colonoscopy in the 3 to 15 months after initiating treatment. METHODS: We identified IBD patients, 18 to 64 years of age, in the IBM MarketScan Commercial Claims and Encounters database as those with ≥3 IBD diagnoses prior to initiation of biologic, small molecule, or immunomodulatory treatment. We excluded patients with prior colectomy and with rheumatologic and other indications for these therapies. Colonoscopies were identified using International Classification of Diseases-Ninth Revision, International Classification of Diseases-Tenth Revision, and Current Procedural Terminology procedure codes. We used Kaplan-Meier methods to estimate the proportion of newly treated IBD patients who received colonoscopy in the 3 to 6 months, 3 to 12 months, and 3 to 15 months following treatment initiation, and stratified trends by year, patient age and sex, and region. RESULTS: From 2013 to 2019, we identified 39 734 initiators of IBD medications (51.9% female, mean age 39.4 years). We observed similar colonoscopy incidence among ulcerative colitis patients (3-6 months: 14.2% [95% confidence interval (CI), 13.6%-14.8%]; 3-12 months: 37.7% [95% CI, 36.8%-38.6%]; 3-15 months: 46.1% [95% CI, 45.2%-47.1%]) and Crohn's disease patients (3-6 months: 11.2% [95% CI, 10.8%-11.6%]; 3-12 months: 32.2% [95% CI, 31.5%-32.9%]; 3-15 months: CD: 40.1% [95% CI, 39.3%-40.8%]). Overall colonoscopy use was slightly higher among women, patients in the Northeast, and those initiating newer biologic therapies. CONCLUSIONS: Fewer than half of newly treated IBD patients underwent colonoscopy within 3 to 15 months of initiating new treatment, suggesting low uptake of treat-to-target endoscopic disease monitoring in real-world practice.

Among 39 734 newly treated, commercially insured inflammatory bowel disease patients in the United States, fewer than half (42%) received colonoscopy in the 3 to 15 months following treatment initiation, suggesting low uptake of STRIDE (Selecting Therapeutic Targets in Inflammatory Bowel Disease)-recommended treat-to-target endoscopic disease activity monitoring in real-world practice.

Auditing Management of Acute Pancreatitis Using Comprehensive Quality Indicators.

OBJECTIVES: Recently, 40 comprehensive quality indicators in various management domains were created. The aim was to determine if these indicators could be used to audit the management of acute pancreatitis. METHODS: A retrospective study of consecutive patients admitted with acute pancreatitis in 2018 was conducted. Adherence rates with the individual quality indicators were calculated and compared between services. RESULTS: A total of 320 patients were included in this study. Twenty-eight of the 40 quality indicators (70%) could be used to audit management retrospectively. The medical service was found to have lower adherence rates for quality indicators 12 (initial assessment and risk stratification domain; 11% vs 22%, P = 0.009), 14 (initial management domain; 72% vs 88%, P = 0.003), and 33 (surgery domain; 83% vs 100%, P = 0.006). The surgical service was noted to have statistically significant lower adherence rates for quality indicators 4, 5, and 6 of the etiology domain (54% vs 72%, P = 0.002; 86% vs 96%, P = 0.004; and 45% vs 71%, P < 0.0001, respectively), and 21 of the nutrition domain (76% vs 93%, P < 0.0001). CONCLUSIONS: We show that these quality indicators can be used to audit the management of acute pancreatitis in specific management domains.

Comparative cost-effectiveness of mailed fecal immunochemical testing (FIT)-based interventions for increasing colorectal cancer screening in the Medicaid population.

BACKGROUND: Mailed reminders to promote colorectal cancer (CRC) screening by fecal immunochemical testing (FIT) have been shown to be effective in the Medicaid population, in which screening is underused. However, little is known regarding the cost-effectiveness of these interventions, with or without an included FIT kit. METHODS: The authors conducted a cost-effectiveness analysis of a randomized controlled trial that compared the effectiveness of a reminder + FIT intervention versus a reminder-only intervention in increasing FIT screening. The analysis compared the costs per person screened for CRC screening associated with the reminder + FIT versus the reminder-only alternative using a 1-year time horizon. Input data for a cohort of 35,000 unscreened North Carolina Medicaid enrollees ages 52 to 64 years were derived from the trial and microcosting. Inputs and outputs were estimated from 2 perspectives-the Medicaid/state perspective and the health clinic/facility perspective-using probabilistic sensitivity analysis to evaluate uncertainty. RESULTS: The anticipated number of CRC screenings, including both FIT and screening colonoscopies, was higher for the reminder + FIT alternative (n = 8131; 23.2%) than for the reminder-only alternative (n = 5533; 15.8%). From the Medicaid/state perspective, the reminder + FIT alternative dominated the reminder-only alternative, with lower costs and higher screening rates. From the health clinic/facility perspective, the reminder + FIT versus the reminder-only alternative resulted in an incremental cost-effectiveness ratio of $116 per person screened. CONCLUSIONS: The reminder + FIT alternative was cost saving per additional Medicaid enrollee screened compared with the reminder-only alternative from the Medicaid/state perspective and likely cost-effective from the health clinic/facility perspective. The results also demonstrate that health departments and state Medicaid programs can efficiently mail FIT kits to large numbers of Medicaid enrollees to increase CRC screening completion.

Real-world evidence on sodium-glucose cotransporter-2 inhibitor use and risk of Fournier's gangrene.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with increased occurrence of Fournier's gangrene (FG), a rare but serious form of necrotizing fasciitis, leading to a warning from the Food and Drug Administration. Real-world evidence on FG is needed to validate this warning. METHODS: We used data from IBM MarketScan (2013-2017) to compare the incidence of FG among adult patients who initiated either SGLT2i, a dipeptidyl peptidase-4 inhibitor (DPP4i), or any non-SGLT2i antihyperglycemic medication. FG was defined using inpatient International Classification of Diseases, Ninth Edition and Tenth Edition diagnosis codes 608.83 and N49.3, respectively, combined with procedure codes for debridement, surgery, or systemic antibiotics. We estimated crude incidence rates (IRs) using Poisson regression, and crude and adjusted HRs (aHR) and 95% CIs using standardized mortality ratio-weighted Cox proportional hazards models. Sensitivity analyses examined the impact of alternative outcome definitions. RESULTS: We identified 211 671 initiators of SGLT2i (n=93 197) and DPP4i (n=118 474), and 305 329 initiators of SGLT2i (n=32 868) and non-SGLT2i (n=272 461). Crude FG IR ranged from 3.2 to 3.8 cases per 100 000 person-years during a median follow-up of 0.51-0.58 years. Compared with DPP4i, SGLT2i initiation was not associated with increased risk of FG for any outcome definition, with aHR estimates ranging from 0.25 (0.04-1.74) to 1.14 (0.86-1.51). In the non-SGLT2i comparison, we observed an increased risk of FG for SGLT2i initiators when using FG diagnosis codes alone, using all diagnosis settings (aHR 1.80; 0.53-6.11) and inpatient diagnoses only (aHR 4.58; 0.99-21.21). CONCLUSIONS: No evidence of increased risk of FG associated with SGLT2i was observed compared with DPP4i, arguably the most relevant clinical comparison. However, uncertainty remains based on potentially higher risk in the broader comparison with all non-SGLT2i antihyperglycemic agents and the rarity of FG. TRIAL REGISTRATION NUMBER: EUPAS Register Number 30018.

Dipeptidyl Peptidase 4 Inhibitors and Risk of Inflammatory Bowel Disease: Real-world Evidence in U.S. Adults.

OBJECTIVE: A recent study raises concerns that dipeptidyl peptidase 4 inhibitors (DPP4i) are associated with increased risk of inflammatory bowel disease (IBD). We evaluated the association between new use of DPP4i and IBD risk compared with other second-line antihyperglycemics. RESEARCH DESIGN AND METHODS: We implemented an active-comparator, new-user cohort design using two U.S. administrative claims databases for commercially insured (MarketScan) and older adult (Medicare fee-for-service, 20% random sample) patients from January 2007 to December 2016. We identified patients, aged ≥18 years, who initiated DPP4i versus sulfonylureas (SUs) or initiated DPP4i versus thiazolidinediones (TZDs) and were without prior diagnosis, treatment, or procedure for IBD. The primary outcome was incident IBD, defined by IBD diagnosis preceded by colonoscopy and biopsy and followed by IBD treatment. We performed propensity score weighting to control for measured baseline confounding, estimated adjusted hazard ratios (aHRs [95% CI]) using weighted Cox proportional hazards models, and used random-effects meta-analysis models to pool aHRs across cohorts. RESULTS: We identified 895,747 eligible patients initiating DPP4i, SU, or TZD; IBD incidence rates ranged from 11.6 to 32.3/100,000 person-years. Over a median treatment duration of 1.09-1.69 years, DPP4i were not associated with increased IBD risk across comparisons. The pooled aHRs for IBD were 0.82 (95% CI 0.41-1.61) when comparing DPP4i (n = 161,612) to SU (n = 310,550) and 0.76 (0.46-1.26) when comparing DPP4i (n = 205,570) to TZD (n = 87,543). CONCLUSIONS: Our population-based cohort study of U.S. adults with diabetes suggests that short-term DPP4i treatment does not increase IBD risk.

Propensity score methods to control for confounding in observational cohort studies: a statistical primer and application to endoscopy research.

BACKGROUND AND AIMS: Confounding is a major concern in nonexperimental studies of endoscopic interventions and can lead to biased estimates of the effects of treatment. Propensity score methods, which are commonly used in the pharmacoepidemiology literature, can effectively control for baseline confounding by balancing measured baseline confounders and risk factors and creating comparable populations of treated and untreated patients. METHODS: We propose the following 5-step checklist to guide the use and evaluation of propensity score methods: (1) select covariates, (2) assess "Table 1" balance in risk factors before propensity score implementation, (3) estimate and implement the propensity score in the study cohort, (4) reassess "Table 1" balance in risk factors after propensity score implementation, and (5) critically evaluate differences between matched and unmatched patients after propensity score implementation. We then applied this checklist to an endoscopy example using a study cohort of 411 adults with newly diagnosed eosinophilic esophagitis (EoE), some of whom were treated with esophageal dilation. RESULTS: We identified 156 patients, aged 18 and older, who were treated with esophageal dilation, and 255 patients who were nondilated. We successfully matched 148 (95%) dilated patients to nondilated patients who had a propensity score within 0.1, based on patient age, sex, race, self-reported food allergy, and presence of narrowing at baseline endoscopy. Crude imbalances were observed before propensity score matching in several baseline covariates, including age, sex, and narrowing; however, propensity score matching was successful in achieving balance across all measured covariates. CONCLUSIONS: We provide an introduction to propensity score methods, including a straightforward checklist for implementing propensity score methods in nonexperimental studies of treatment effectiveness. Moreover, we demonstrate the advantage of using "Table 1" as a simple but effective diagnostic tool for evaluating the success of propensity score methods in an applied example of esophageal dilation in EoE.

Comparative effectiveness of mailed reminders with and without fecal immunochemical tests for Medicaid beneficiaries at a large county health department: A randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) screening is effective but underused. Screening rates are lower among Medicaid beneficiaries versus other insured populations. No studies have examined mailed fecal immunochemical testing (FIT)-based outreach programs for Medicaid beneficiaries. METHODS: In a patient-level randomized controlled trial, a mailed CRC screening reminder plus FIT, sent from an urban health department to Medicaid beneficiaries, was compared with the same reminder without FIT. The reminder group could request FIT. Completed FIT kits were processed by the health department laboratory. Respondents were notified of normal results by mail. Abnormal results were given via phone by a patient navigator who provided counselling and assistance with follow-up care. The primary outcome was FIT return. RESULTS: In all, 2144 beneficiaries at average CRC risk were identified, and there was no evidence of screening with Medicaid claims data. To the reminder+FIT group, 1071 were randomized, and 1073 were randomized to the reminder group; 307 (28.7%) in the reminder+FIT group and 347 (32.3%) in the reminder group were unreachable or ineligible (previous screening). The FIT return rate was significantly higher in the reminder+FIT group than the reminder group (21.1% vs 12.3%; difference, 8.8%; 95% confidence interval, 3.7%-13.9%; P < .01). Eighteen individuals (7.2%) who completed FIT tests had abnormal results, and 15 were eligible for follow-up colonoscopy; 66.7% (n = 10) completed follow-up colonoscopy. CONCLUSIONS: A health department-based, mailed FIT program targeting Medicaid beneficiaries was feasible. Including a FIT kit resulted in greater screening completion than a reminder letter alone. Further research is needed to understand the comparative cost-effectiveness of these interventions.

Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder.

CONTEXT: The administration of nicotine transiently improves many neurobiological and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder. OBJECTIVE: Because α4ß2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4ß2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans. DESIGN: A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder to examine the effects of varenicline on biomarkers at 2 weeks (short-term treatment) and 8 weeks (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4ß2-specific effects while minimizing adverse effects. SETTING: Outpatient clinics. PARTICIPANTS: A total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Intervention Varenicline. MAIN OUTCOME MEASURES: Prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention. RESULTS: A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P = .006), (2) reduced startle reactivity (P = .02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P = .03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners' Continuous Performance Test. Clinically, there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose). CONCLUSIONS: Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biological deficits.