Society: AGA

INTRODUCTION: A number of medications have been implicated as primary risk factors for microscopic colitis (MC) and guidelines recommend discontinuation of these medications as part of MC management. However, there are few epidemiologic studies that have attempted to explore a causal relationship between medications and MC.

METHODS: We conducted a cohort study of all residents in Sweden since 2004 over the age of 60 years to examine the association between select medications and the risk of MC. For each medication, new initiators were identified at the time of their first dispensed drug (index date for users) and matched to non-users at the time of dispense of any other medication (index date for non-users) within 6 months of index date for users. Exact 1:1 matching was done according to age, sex, calendar year, healthcare utilization defined by number of prior dispensed medications and encounters for inpatient visits and outpatient subspecialty care, and GI-specific utilizations, including number of endoscopies and GI-related encounters. End of follow up was defined as death, emigration, diagnosis of MC, ascertained through linkage to nationwide histopathology cohort, or December 31^st, 2017, whichever came first. Proportional hazard models were fit to obtain effect estimates. To assess the validity of our models, use of coumadin and beta blockers were defined as negative control exposures while colonoscopy with normal biopsies was defined as a negative control outcome.

RESULTS: We identified 3,278,547 residents of Sweden over the age of 60 years with at least one drug prescription from 2006-2017 which was used to build nine separate cohorts of drug user versus non-users: proton pump inhibitors (PPI, n = 2,487,228), selective serotonin reuptake inhibitors (SSRI, n = 1,232,510), angiotensin converting enzyme inhibitors (ACE-I, n = 2,151,098), angiotensin receptor blockers (n = 1,422,642), Statins (n = 2,374552), NSAIDs (n = 2,581,372), Anti-Parkinson drugs (APD, n = 289,930), coumadin (n = 708,582), and beta blockers (BBs, n = 2,480,988). In an intention-to-treat analysis, PPIs (HR=1.43 [1.32-1.56]), SSRIs (HR= 2.32 [2.07-2.60]), ARBs (HR= 1.26 [1.13-1.42]), and NSAIDs (1.13 [1.06-1.22]) associated with increased risk of MC but equally so with colonoscopy with normal mucosa (Table 1). Our results were similar in as-treated analyses, where participants were censored after discontinuation of medications.

CONCLUSION: In a nationwide cohort study, we observed an increased risk of MC with initiation of previously implicated medications. However, most of these associations were equally observed with receiving a colonoscopy with normal biopsies suggesting that such medication use was associated with undergoing colonoscopy and not MC. These findings suggest that previously observed associations were likely related to surveillance bias.

BACKGROUND: Ulcerative colitis (UC) is treated with infliximab (IFX). However, up to 45% of patients on IFX have sub-therapeutic drug levels, which is associated with loss of treatment response. Despite improved outcomes with proactive therapeutic drug monitoring (TDM), only 37% of gastroenterologists use proactive monitoring for IBD, with the primary barrier being insurance coverage (78%).

STUDY DESIGN: Cost-effectiveness analysis comparing proactive TDM, reactive TDM, and no TDM in UC patients on IFX.

METHODS: We developed a Markov model for patients on IFX therapy that tracked IFX dose, antibody levels, and IFX drug concentrations over a five-year time horizon. IFX concentration and antibody status were measured every six months or at the time of a flare under proactive TDM, while they were only measured during a flare under reactive TDM. Patients were initialized on IFX monotherapy at 5 mg/kg. Management decisions for each strategy are depicted in Figure 1. Patients entering a flare state incurred a reduced utility score and risk of further complications (hospitalization, surgery, readmission, and/or transition to other agents). The cost and utility values for Markov states, risk of complications, and transition probabilities for second-line agents were estimated from the literature. Transition probabilities for the IFX states are uncertain; thus, we used the incremental mixture importance sampling algorithm and specified plausible ranges to calibrate these parameters. We matched model outputs to specific calibration targets: the proportion of patients who fail IFX and those who are post-surgical at the one- and five-year marks.

RESULTS: Proactive TDM dominated other approaches, with an approximate cost of $135,000 and a utility of 3.87 QALYs per patient (Figure 2). In the proactive TDM strategy, the discovery of anti-drug antibodies at baseline initially resulted in higher rates of IFX discontinuation. However, long-term, proactive TDM allowed a greater proportion of patients to remain on IFX—mitigating the risk and associated costs of flares and complications. At the five-year mark, 27% of patients remained on IFX in the proactive TDM group compared to 21% for patients in both the reactive and no TDM groups. In one-way sensitivity analyses, we varied medication and test costs, surgery and hospitalization costs, risk of flare at different drug levels, and baseline distribution of drug levels and presence of antibodies. In each case, proactive TDM was cost-saving compared to the other TDM strategies for plausible parameter ranges.

CONCLUSION: Proactive monitoring in UC patients on IFX was cost-saving compared to reactive monitoring, primarily by identifying patients with high antibody levels and preventing antibodies that occur at lower IFX levels. Further studies to provide more precision to the benefit of proactive monitoring are warranted.

Background: In 2019, the American Gastrointestinal Association (AGA) published a guideline on the gastrointestinal evaluation of asymptomatic iron deficiency anemia (IDA). The guideline included a strong recommendation for post-menopausal women and men to undergo bidirectional endoscopy, and a conditional recommendation for pre-menopausal women. The AGA also suggests that all patients undergo non-invasive testing for H. pylori and celiac disease. This study aimed to evaluate guideline adherence in the outpatient primay care setting in the University of Pennsylvania Health System.

Methods: A retrospective analysis of outpatient encounters in the primary care setting with a coded diagnosis of IDA from January to July 2022 was conducted. In order to utilize the AGA's definition of patients with IDA, manual chart review was conducted to determine inclusion criteria: a ferritin level less than or equal to 45 ng/mL, asymptomatic with no chronic or overt blood loss, and age > 18 years. Data were abstracted into REDCap including age, sex, self-reported race, menopausal status, as well as outcome variables of non-invasive testing, endoscopy utilization, and treatment with iron. Chi-square analyses and fisher's exact tests were conducted in STATA.

Results: There were 835 patients with a coded diagnosis of IDA whose charts were manually reviewed. Of these, 50 met inclusion criteria. The median age was 46 years (IQR 31-56). Self-identified race in the cohort was 67% Black, 27% White, 4% Asian, and 2% Other. Of patients with IDA (n=50), 67% of men and post-menopausal women had a colonoscopy ordered, compared to 23% of pre-menopausal women (p=0.002). For upper endoscopy, 62% of men and post-menopausal women had it ordered, compared to 23% of pre-menopausal women (p=0.005). Of those, only 32% of patients had upper endoscopy and colonoscopy completed. For non-invasive testing, celiac testing was performed in 27% of patients, and H. pylori testing was performed in 14% of patients. In terms of treatment, 48% of patients received oral iron and 29% of patients received intravenous iron, with no significant differences between menopausal women and men, and pre-menopausal women (p=0.36, 0.62, respectively).

Conclusion: There is significant opportunity to improve adherence to AGA clinical guideline recommendations. For men and post-menopausal women, there is a strong recommendation to pursue bidirectional endoscopy, but only 67% were ordered a colonoscopy and 62% an upper endoscopy. Lower rates are expected for pre-menopausal women given the conditional recommendation for this population. There is notable room to improve adherence to non-invasive testing for celiac disease and H. pylori. These data will be used as baseline data for an electronic health record intervention that will notify providers of AGA recommendations at the point-of-care.

INTRODUCTION:
Acute pancreatitis (AP) is a common cause for hospitalization with local and systemic complications. Numerous AP guidelines have been published but there is comparatively little data on impact of interventions to improve adherence to quality metrics. The aim of this study was to assess the impact of a multifaced quality improvement (QI) intervention using education, electronic health record (EHR) prompts, education, and performance measurement upon AP quality metrics adherence and outcomes in an integrated network of hospitals.

METHODS:
We conducted a prospective QI project at an integrated healthcare system consisting of 8 hospitals beginning January 2021. Interventions included stakeholder engagement, AP consensus guideline development, refinement of an EHR orderset to reflect AP best practice, provider education, and ongoing performance evaluation (Figure 1). A literature search identified all relevant AP guidelines published within the past decade; all proposed quality metrics were abstracted. A Delphi approach among all stakeholders was utilized to come to an agreement on which quality metrics were felt to be most impactful. AP process and outcome measures prior to (8/2020-7/2021) and following QI intervention (8/2021-10/2022) are reported.

RESULTS:
Stakeholders identified the following metrics as best supported by high-quality evidence: use of Lactated Ringer’s (LR) for hydration within the first 24 hours (“LR % of Hydration”), reduction of CT scan utilization within first 24 hours (“early CT utilization”), reduction in nil per os (NPO) status beyond 5 days (“prolonged NPO status”), reduction in total parenteral nutrition (TPN) utilization, and decrease in opioid use.
Over the entire timeframe, there were 2,227 distinct AP encounters. The use of the AP EHR orderset increased from 5.8% at baseline to 18.8% (p<0.001) in the most recent quarter (Figure 2). LR % of hydration was measured as the proportion of intravenous fluids delivered within first 24 hours utilizing LR. There was a modest increase in LR % of hydration during the study period (from 46.6% to 62.4%; p=0.01). However, the mean length of stay did not differ during the study period (overall mean 5.2 days). Similarly, there was no decrease in early CT scan utilization. Prolonged NPO status and TPN utilization rates remained low throughout the study period without significant impact from the QI intervention. Similarly, there was no impact of the QI interventions on mean days on opioids (overall mean 4.0 days).

DISCUSSION:
Despite a comprehensive QI collaborative effort to improve guideline-based care of AP patients, there was a very modest impact on the quality of care delivered, mainly through greater adherence to use of LR resuscitation. Further work is needed to identify effective and durable solutions to improve the value of AP care and associated outcomes.

Overview of Acute Pancreatitis Quality Improvement Efforts. At study onset, we assembled a group of stakeholders from multiple disciplines in our 8-hospital collaborative. Cornerstones of the QI effort included developing a standardized approach to acute pancreatitis management, modifications of an orderset, provider education, and ongoing performance evaluation.

Overview of Acute Pancreatitis Quality Improvement Efforts. At study onset, we assembled a group of stakeholders from multiple disciplines in our 8-hospital collaborative. Cornerstones of the QI effort included developing a standardized approach to acute pancreatitis management, modifications of an orderset, provider education, and ongoing performance evaluation.

After initiation of the acute pancreatitis collaborative, there was a significant increase in use of orderset usage (seen as gray line in all panels). A) Throughout the study period, there was a significant increase in usage of LR as a hydration fluid within the first 24 hours of resuscitation. However, there was no decrease in CT scan utilization. B) There was no reduction in length of stay or opioid use during the study period. C) Usage of TPN and prolonged NPO status (beyond 5 days) remained low during the study period but was not impacted by the QI efforts.

After initiation of the acute pancreatitis collaborative, there was a significant increase in use of orderset usage (seen as gray line in all panels). A) Throughout the study period, there was a significant increase in usage of LR as a hydration fluid within the first 24 hours of resuscitation. However, there was no decrease in CT scan utilization. B) There was no reduction in length of stay or opioid use during the study period. C) Usage of TPN and prolonged NPO status (beyond 5 days) remained low during the study period but was not impacted by the QI efforts.

Justin Boike

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