Active surveillance pharmacovigilance for Clostridioides difficile infection and gastrointestinal bleeding: an analytic framework based on case-control studies.

BACKGROUND: Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB). METHODS: We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score. FINDINGS: For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated. INTERPRETATION: These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions. FUNDING: U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Suboptimal Performance of Microscopic Colitis Diagnosis Codes: A Bottleneck for Epidemiologic Insights.

INTRODUCTION: Administrative health data could contribute to generalizable microscopic colitis insights, but International Classification of Diseases (ICD) codes for microscopic colitis have not been validated. METHODS: We identified individuals who received care for diarrhea in the Veterans Health Administration and classified them by receipt of microscopic colitis ICD codes. We reviewed random samples of charts to calculate the positive predictive value (PPV) and negative predictive value (NPV). We then calculated the sensitivity and specificity in clinically relevant cohorts. RESULTS: The PPV was 0.790 and the NPV was 0.995. In a cohort of individuals with diarrhea who underwent colonoscopy, the sensitivity and specificity were 0.734 and 0.996, respectively. CONCLUSION: Alternative ascertainment methods for microscopic colitis are needed because ICD codes have suboptimal performance.

Projected impact of anti-obesity pharmacotherapy use on racial and ethnic disparities in adolescent obesity.

BACKGROUND: Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti-obesity pharmacotherapy for adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated. OBJECTIVES: To model changes in obesity prevalence with increasing utilization of anti-obesity pharmacotherapy among adolescents. METHODS: Data representative of American adolescents ages 12-17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre-pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%-100%, stratified by race and ethnicity. RESULTS: Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non-Hispanic White youth, with prevalence among Non-Hispanic Black and Mexican American youth ranging from 40%-60% higher to 90%-120% higher, respectively. CONCLUSIONS: Increasing utilization of anti-obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity-related disparities.

Disparities in Guideline-Recommended Statin Use for Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and Gender : A Nationally Representative Cross-Sectional Analysis of Adults in the United States.

BACKGROUND: Although statins are a class I recommendation for prevention of atherosclerotic cardiovascular disease and its complications, their use is suboptimal. Differential underuse may mediate disparities in cardiovascular health for systematically marginalized persons. OBJECTIVE: To estimate disparities in statin use by race-ethnicity-gender and to determine whether these potential disparities are explained by medical appropriateness of therapy and structural factors. DESIGN: Cross-sectional analysis. SETTING: National Health and Nutrition Examination Survey from 2015 to 2020. PARTICIPANTS: Persons eligible for statin therapy based on 2013 and 2018 American College of Cardiology/American Heart Association blood cholesterol guidelines. MEASUREMENTS: The independent variable was race-ethnicity-gender. The outcome of interest was use of a statin. Using the Institute of Medicine framework for examining unequal treatment, we calculated adjusted prevalence ratios (aPRs) to estimate disparities in statin use adjusted for age, disease severity, access to health care, and socioeconomic status relative to non-Hispanic White men. RESULTS: For primary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors among non-Hispanic Black men (aPR, 0.73 [95% CI, 0.59 to 0.88]) and non-Mexican Hispanic women (aPR, 0.74 [CI, 0.53 to 0.95]). For secondary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors for non-Hispanic Black men (aPR, 0.81 [CI, 0.64 to 0.97]), other/multiracial men (aPR, 0.58 [CI, 0.20 to 0.97]), Mexican American women (aPR, 0.36 [CI, 0.10 to 0.61]), non-Mexican Hispanic women (aPR, 0.57 [CI, 0.33 to 0.82), non-Hispanic White women (aPR, 0.69 [CI, 0.56 to 0.83]), and non-Hispanic Black women (aPR, 0.75 [CI, 0.57 to 0.92]). LIMITATION: Cross-sectional data; lack of geographic, language, or statin-dose data. CONCLUSION: Statin use disparities for several race-ethnicity-gender groups are not explained by measurable differences in medical appropriateness of therapy, access to health care, and socioeconomic status. These residual disparities may be partially mediated by unobserved processes that contribute to health inequity, including bias, stereotyping, and mistrust. PRIMARY FUNDING SOURCE: National Institutes of Health.

Patient Knowledge, Risk Perception, and Barriers to Barrett's Esophagus Screening.

INTRODUCTION: Most patients with esophageal adenocarcinoma (EAC) do not have a previous diagnosis of Barrett's esophagus (BE), demonstrating a failure of current screening practices. An understanding of patient attitudes and barriers is essential to develop and implement interventions to improve BE screening adherence. METHODS: We conducted a Web-based survey of patients aged >50 years with chronic gastroesophageal reflux disease at 3 academic medical centers and 1 affiliated safety net health systems. Survey domains included patient characteristics, endoscopy history, familiarity with screening practices, perceived BE/EAC risk, and barriers to screening. RESULTS: We obtained a response rate of 22.6% (472/2,084) (74% men, mean age 67.9 years). Self-identified race and ethnicity of participants was 66.5% non-Hispanic White, 20.0% non-Hispanic Black, 13.4% other race, and 7.1% Hispanic. Screening for BE was recommended in only 13.2%, and only 5.3% reported previous screening. Respondents had notable gaps in knowledge about screening indications; only two-thirds correctly identified BE risk factors and only 19.5% believed BE screening was needed for gastroesophageal reflux disease. More than 1 in 5 respondents believed they would get BE (31.9%) or EAC (20.2%) but reported barriers to screening. Compared with White respondents, more Black respondents were concerned about getting BE/EAC and interested in screening but report higher barriers to screening. DISCUSSION: Patients at risk for BE, particularly racial and ethnic minorities, are worried about developing EAC but rarely undergo screening and have poor understanding of screening recommendations.

Delays Related to Prior Authorization in Inflammatory Bowel Disease.

BACKGROUND: Delays in advancing to biologic therapies are associated with adverse outcomes in inflammatory bowel disease (IBD). Insurer-mandated prior authorizations have been linked to prolonged medication initiation times. We hypothesized that prior authorizations are associated with prolonged biologic initiation time and increased IBD-related healthcare utilization among children with IBD. METHODS: We performed a retrospective cohort study of 190 pediatric patients with IBD initiating biologics at a tertiary care hospital to measure the association between prior authorization, biologic initiation time (physician recommendation to first dose), and healthcare utilization (hospitalization, surgery, or emergency department visit). Demographic, insurance, and disease severity-related covariables were collected. Multivariable linear regression was used to measure the association between prior authorization and biologic initiation time. Propensity score methods were used to measure the associations between prior authorization and IBD-related healthcare utilization within 180 days and corticosteroid dependence at 90 days, with adjustment for insurance type, demographics, and disease severity-related characteristics. RESULTS: Median biologic initiation time was 21 days. Prior authorization and complicated prior authorizations (requiring appeal, step therapy, or peer-to-peer review) were associated with 10.2-day (95% confidence interval [CI] 8.2 to 12.3) and 24.6-day (95% CI 16.4 to 32.8) increases in biologic initiation time, respectively. Prior authorizations increased the likelihood of IBD-related healthcare utilization within 180 days by 12.9% (95% CI 2.5 to 23.4) and corticosteroid dependence at 90 days by 14.1% (95% CI 3.3 to 24.8). CONCLUSIONS: Prior authorizations are associated with prolonged biologic initiation time and increased IBD-related healthcare utilization. Minimizing prior authorization-related delays may expedite biologic delivery and reduce the risk of IBD-related healthcare utilization.

Magnitude and Time-Trend Analysis of Postendoscopy Esophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Identification of postendoscopy esophageal adenocarcinoma (PEEC) among Barrett's esophagus (BE) patients presents an opportunity to improve survival of esophageal adenocarcinoma (EAC). We aimed to estimate the proportion of PEEC within the first year after BE diagnosis. METHODS: Multiple databases (Medline, Embase, Scopus, and Cochrane databases) were searched until September 2020 for original studies with at least 1-year follow-up evaluation that reported EAC and/or high-grade dysplasia (HGD) in the first year after index endoscopy in nondysplastic BE, low-grade dysplasia, or indefinite dysplasia. The proportions of PEEC defined using EAC alone and EAC+HGD were calculated by dividing EAC or EAC+HGD in the first year over the total number of EAC or EAC+HGD, respectively. RESULTS: We included 52 studies with 145,726 patients and a median follow-up period of 4.8 years. The proportion of PEEC (EAC) was 21% (95% CI, 13-31) and PEEC (EAC+HGD) was 26% (95% CI, 19-34). Among studies with nondysplastic BE only, the PEEC (EAC) proportion was 17% (95% CI, 11-23) and PEEC (EAC+HGD) was 14% (95% CI, 8-19). Among studies with 5 or more years of follow-up evaluation, the PEEC (EAC) proportion was 10% and PEEC (EAC+HGD) was 19%. Meta-regression analysis showed a strong inverse relationship between PEEC and incident EAC (P < .001). The PEEC (EAC) proportion increased from 5% in studies published before 2000 to 30% after 2015. Substantial heterogeneity was observed for most analyses. CONCLUSIONS: PEEC accounts for a high proportion of HGD/EACs and is proportional to reduction in incident EAC. Using best endoscopic techniques now and performing future research on improving neoplasia detection through implementation of quality measures and educational tools is needed to reduce PEEC.

Risk for Post-Colonoscopy Irritable Bowel Syndrome in Patients With and Without Antibiotic Exposure: A Retrospective Cohort Study.

BACKGROUND & AIMS: Laboratory studies have demonstrated that antibiotic use in conjunction with bowel purgatives causes alterations to the gut microbiota. Because gut microbiota changes may be a trigger for the development of irritable bowel syndrome (IBS), we sought to assess whether individuals who undergo bowel cleansing for colonoscopy and have concurrent antibiotic exposure develop IBS at higher rates than individuals who undergo colonoscopy without antibiotic exposure. METHODS: We used data from Optum's de-identified Clinformatics Data Mart Database in the United States to study a cohort of 50- to 55-year-olds who underwent screening colonoscopy. Individuals exposed to antibiotics within 14 days of colonoscopy were propensity-score matched to individuals who were not exposed to antibiotics around colonoscopy. The primary outcome was a new IBS diagnosis, and the composite outcome was a new claim for IBS, IBS medications, or IBS symptoms. The association of antibiotic exposure and the outcomes was calculated using Cox proportional hazards regression. RESULTS: There were 408,714 individuals who met criteria for the screening colonoscopy cohort. Of these, 24,617 (6.0%) were exposed to antibiotics around the time of colonoscopy, and they were propensity-score matched to 24,617 individuals not exposed to antibiotics. There was no statistically significant association between antibiotic use and IBS (hazard ratio, 1.11; 95% confidence interval, 0.89-1.39), but there was a weak association between antibiotic use and the composite outcome (hazard ratio, 1.12; 95% confidence interval, 1.02-1.24; number needed to harm, 94). CONCLUSIONS: Individuals concurrently exposed to antibiotics and bowel purgative had slightly higher rates of surrogate IBS outcomes compared with matched controls who did not receive antibiotics concurrently with bowel purgative.

Endoscopy Is Not Associated with Infectious Adverse Events After Hematopoietic Cell Transplantation: A Retrospective Cohort Study.

BACKGROUND: Patients with recent hematopoietic cell transplantation (HCT) are considered high risk for gastrointestinal endoscopy due to the potential for procedural bacterial translocation. Prior studies investigating these risks do not account for the higher baseline rate of infectious complications among those who are immunocompromised. We performed a retrospective cohort study of patients with recent HCT who underwent endoscopy and their matched controls who did not undergo endoscopy. METHODS: We identified patients who underwent HCT followed by upper and/or lower endoscopy at the University of Pennsylvania from 2000 to 2018. Individuals were matched 1:1 by age, sex, and type of HCT to controls who underwent HCT without subsequent endoscopy. Infectious adverse events were assessed by Sepsis-3 and Sepsis-2 criteria. Factors associated with infectious adverse events after endoscopy/index date were assessed using multivariable conditional logistic regression. RESULTS: We identified 149 patients who underwent HCT and endoscopy and 149 matched controls who underwent HCT without endoscopy. Sepsis-3 infectious adverse events occurred in 3.4% of patients in each group. Sepsis-2 infectious adverse events occurred in 20.1% of patients who underwent endoscopy compared to 19.5% of controls. There was no association between endoscopy and Sepsis-2 infectious adverse events in the multivariable regression analysis (adjusted odds ratio 1.65, 95% CI 0.51-5.26). CONCLUSIONS: When compared to controls with similar immune statuses, patients who underwent endoscopy after HCT did not have a higher risk of infectious adverse events. These results may inform clinical decision making regarding the risks and benefits of endoscopic management after HCT.

Characterization of Prevalent, Post-Endoscopy, and Incident Esophageal Cancer in the United States: A Large Retrospective Cohort Study.

BACKGROUND & AIMS: Efforts to assess and improve the effectiveness of Barrett's esophagus (BE) screening and surveillance are ongoing in the United States. Currently, there are limited population-based data in the United States to guide these efforts. METHODS: We performed a retrospective cohort study using data from large commercial and Medicare Advantage health plans in the United States from 2004 - 2019. We identified individuals with BE and analyzed the proportion who developed EAC. EACs were classified as prevalent EAC (diagnosed within 30 days of index endoscopy), post-endoscopy esophageal adenocarcinoma (PEEC, diagnosed 30 - 365 days after index endoscopy), and incident EAC (diagnosed 365 days or more after index endoscopy). Using this cohort, we performed a nested case-control study to identify factors associated with prevalent EAC at BE diagnosis and study healthcare utilization prior to BE diagnosis. RESULTS: We identified 50,817 individuals with incident BE. Of the 366 who developed EAC, 67.2%, 13.7%, and 19.1% were diagnosed with prevalent EAC, PEEC, and incident EAC respectively. Factors positively associated with prevalent EAC versus BE without prevalent EAC included male sex, dysphagia, weight loss, and Charlson-Deyo comorbidity score. In those with prevalent EAC, most patients with dysphagia or weight loss had their symptoms first recorded within three months of EAC diagnosis. Healthcare utilization rates were similar between those with and without prevalent EAC. CONCLUSIONS: Two-thirds of EACs among individuals with BE are diagnosed at the time of BE diagnosis. Additionally, PEEC accounts for 14% of these EACs. These results may guide future research studies that investigate novel BE diagnostic strategies that reduce the morbidity and mortality of EAC.

Long-term Outcomes Following Multiply Recurrent Clostridioides difficile Infection and Fecal Microbiota Transplantation.

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome. METHODS: This retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created 2 pairwise comparisons: mrCDI vs non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs mrCDI without FMT. RESULTS: We found no significant association between mrCDI (vs non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR = 0.86; 0.47-1.56), psoriasis (HR = 0.72; 0.23-2.27), diabetes (aHR = 0.97; 0.67-1.40), hypertension (aHR = 1.05; 0.76-1.44), myocardial infarction (aHR = 0.82; 0.63-1.06), stroke (aHR = 0.83; 0.62-1.12), or irritable bowel syndrome (HR = 0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs mrCDI without FMT) and diabetes (aHR = 0.92; 0.27-3.11), hypertension (aHR = 1.41; 0.64-3.15), stroke (aHR = 1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR = 0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR = 1.68; 1.01-2.81). CONCLUSION: Relative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.

Patient Factors Associated With Gastroesophageal Reflux Disease Diagnostic Evaluation Strategies: A Retrospective Cohort Study Using Real-World Evidence From a Large U.S. Medical Claims Database.

Background and Aims: Barrett's esophagus (BE) screening is not highly utilized in the United States, and there are few data describing providers' approach to screening. To fill this gap and guide the implementation of future BE screening strategies, we studied evaluation practice patterns for gastroesophageal reflux disease (GERD) by nongastroenterologists. Methods: We performed a retrospective cohort study of patients with chronic GERD using health claims data from the United States between 2005 and 2019. We used up to 5 years of data after the diagnosis of chronic GERD to determine patient factors associated with completion of a gastroenterology encounter. We also identified patient factors associated with whether the first gastroenterology encounter was a direct-access upper endoscopy or an office visit. Results: We identified 484,023 patients diagnosed with chronic GERD by a nongastroenterology provider. The cumulative incidence of completing a gastroenterology encounter within 5 years was 38.7%. Gastrointestinal symptoms, such as dysphagia (adjusted hazard ratio [aHR] = 2.11, 95% confidence interval [CI] = 1.94-2.30), abdominal pain (aHR = 1.89, 95% CI = 1.85-1.94), and melena (aHR = 1.73, 95% CI = 1.65-1.82), were strongly associated with completion of a gastroenterology encounter. The patient factors strongly associated with direct-access upper endoscopy included dysphagia (aHR = 1.68, 95% CI = 1.52-1.85), weight loss (aHR = 1.46, 95% CI = 1.28-1.63), and melena (aHR = 1.42, 95% CI = 1.28-1.56). Conclusion: A total of 38.7% of patients with chronic GERD complete a gastroenterology encounter within 5 years of diagnosis, and gastrointestinal alarm symptoms are the most strongly associated factors for receiving gastroenterology care. These findings highlight the importance of incorporating primary care providers in the development of new BE screening programs.

Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers. While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines, there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS, including small intestinal cancer (SIC) and urinary tract cancer (UTC). Given the limited evidence, guidelines do not consistently recommend surveillance for SIC and UTC, and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance recommendations. AIM: To study factors associated with SIC and UTC surveillance uptake and outcomes in LS. METHODS: This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral center. Included individuals had a pathogenic or likely pathogenic variant in MLH1, MSH2, MSH6, PMS2, or EPCAM, or were a confirmed obligate carrier, and had at least one documented visit to our center. Information regarding SIC and UTC surveillance was captured for each individual, and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center's dedicated high-risk LS clinic between January 1, 2017 and October 29, 2020. During these initial management visits, all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC surveillance. Statistical analysis using Pearson's chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance, and a P value below 0.05 was deemed statistically significant. RESULTS: Of 317 individuals with LS, 86 (27%) underwent a total of 105 SIC surveillance examinations, with 5 leading to additional work-up and no SICs diagnosed. Additionally, 99 (31%) patients underwent a total of 303 UTC surveillance examinations, with 19 requiring further evaluation and 1 UTC identified. Of 155 individuals who had an initial LS management visit between January 1, 2017 and October 29, 2020, 63 (41%) chose to undergo SIC surveillance and 58 (37%) chose to undergo UTC surveillance. However, only 26 (41%) and 32 (55%) of those who initially chose to undergo SIC or UTC surveillance, respectively, successfully completed their surveillance examinations. Individuals with a pathogenic variant in MSH2 or EPCAM were more likely to initially choose to undergo SIC surveillance (P = 0.034), and older individuals were more likely to complete SIC surveillance (P = 0.007). Choosing to pursue UTC surveillance was more frequent among older individuals (P = 0.018), and females more frequently completed UTC surveillance (P = 0.002). Personal history of cancer and family history of SIC or UTC were not significantly associated with electing nor completing surveillance. Lastly, the provider discussing SIC/UTC surveillance was significantly associated with subsequent surveillance choices. CONCLUSION: Pursuing and completing SIC/UTC surveillance in LS is influenced by several factors, however broad incorporation in LS management is likely unhelpful due to low yield and frequent false positive results.

The Volume-Outcome Effect Calls for Centralization of Care in Esophageal Adenocarcinoma: Results From a Large National Cancer Registry.

INTRODUCTION: Using the National Cancer Database, we assessed the relationship between facility overall esophageal adenocarcinoma (EAC) case volume and survival. METHODS: We categorized facilities into volume quintiles based on annual EAC patient volume and performed a multivariable Cox proportional hazards regression between facility patient volume and survival. RESULTS: In a cohort of 116,675 patients, facilities with higher vs lower (≥25 vs 1-4 cases) annual EAC patient volume demonstrated improved survival (adjusted hazard ratio: 0.80. 95% confidence interval: 0.70-0.91). DISCUSSION: This robust volume-outcome effect calls for centralization of care for EAC patients at high annual case volume facilities.

Association Between Statin Use at the Time of Intra-abdominal Surgery and Postoperative Adhesion-Related Complications and Small-Bowel Obstruction.

Importance: Adhesion-related complications (ARCs), including small-bowel obstruction, are common complications of intra-abdominal surgery. Statins, which have antifibrotic pleiotropic effects, inhibit adhesion formation in murine models but have not been assessed in humans. Objective: To assess whether statin use at the time of intra-abdominal surgery is associated with a reduction in ARCs. Design, Setting, and Participants: These 2 separate retrospective cohort studies (The Health Improvement Network [THIN] and Optum's Clinformatics Data Mart [Optum]) compared adults receiving statins with those not receiving statins at the time of intra-abdominal surgery. Individuals undergoing intra-abdominal surgery from January 1, 1996, to December 31, 2013, in the United Kingdom and from January 1, 2000, to December 31, 2016, in the US were included in the study. Those with obstructive events before surgery or a history of inflammatory bowel disease were excluded. Data analysis was performed from September 1, 2012, to November 24, 2020. Exposure: The primary exposure was statin use at the time of surgery. Main Outcomes and Measures: The primary outcome was ARCs, defined as small-bowel obstruction or need for adhesiolysis, occurring after surgery. Sensitivity analyses included statin use preceding but not concurrent with surgery, fibrate use, and angiotensin-converting enzyme inhibitor use. All analyses were adjusted for age, sex, and conditions associated with microvascular disease, such as hypertension, hyperlipidemia, obesity, and tobacco use; surgical approach and site; and diagnosis of a malignant tumor. Results: A total of 148 601 individuals met the inclusion criteria for THIN (mean [SD] age, 49.6 [17.7] years; 70.1% female) and 1 188 217 for Optum (mean [SD] age, 48.2 [16.4] years; 72.6% female). A total of 2060 participants (1.4%) experienced an ARC in THIN and 54 136 (4.6%) in Optum. Statin use at the time of surgery was associated with decreased risk of ARCs (THIN: adjusted hazard ratio [HR], 0.81; 95% CI, 0.71-0.92; Optum: adjusted HR, 0.92; 95% CI, 0.90-0.95). Similar associations were appreciated between statins and small-bowel obstruction (THIN: adjusted HR, 0.80; 95% CI, 0.70-0.92; Optum: adjusted HR, 0.88; 95% CI, 0.85-0.91). Conclusions and Relevance: This study's findings suggest that, among individuals in 2 separate cohorts undergoing intra-abdominal surgery, statin use may be associated with a reduced risk of postoperative ARCs. Statins may represent an inexpensive, well-tolerated pharmacologic option for preventing ARCs.

Development and Validation of an Administrative Codes Algorithm to Identify Abdominal Surgery and Bowel Obstruction in Patients With Inflammatory Bowel Disease.

Background: Validated administrative codes (CPT and ICD) can permit the use of large databases to study diseases and outcomes. The aim of this study was to validate administrative codes for surgery and obstructive complications in patients with inflammatory bowel disease (IBD). Methods: We performed a retrospective study of IBD patients within the Veterans Affairs Health Administration (VA) from 2000 to 2015 with administrative codes for bowel surgery and complications validated by chart review. Positive predictive values (PPVs) and negative predictive value (NPV) were calculated. Results: The PPV for bowel surgery was 96.4%; PPV of obstruction codes for bowel obstruction was 80.5% (95% confidence interval: 69.1%, 89.2%). Conclusions: CPT and ICD codes for abdominal surgery and obstructive complications can be accurately utilized in IBD patients in VA.

Identification of the Most Effective Position for Ustekinumab in Treatment Algorithms for Crohn's Disease.

BACKGROUND & AIMS: Ustekinumab is a monoclonal antibody against interleukin 12 and interleukin 23 that has been approved by the Food and Drug Administration for treatment of Crohn's disease (CD). We sought to identify the ideal position for ustekinumab in treatment algorithms for CD. METHODS: We constructed a Markov model to identify an optimal treatment sequence for CD that included ustekinumab for 1 year or more. The base case was a 35-year old male with moderate to severe CD who had not previously received biologic or immunomodulator therapy. The standard of care treatment algorithm was defined as initial therapy with infliximab and azathioprine, followed by adalimumab and azathioprine, vedolizumab, and lastly surgical resection. The model assessed positions for ustekinumab before standard of care, ustekinumab after infliximab and azathioprine but before the remaining treatments, after infliximab, azathioprine, and adalimumab but before vedolizumab and surgery, or after the other biologics but before surgery. We derived transition probabilities and quality adjusted life years (QALYs) from relevant trials, observational studies, and time trade-off analyses. Primary analyses consisted of first order Monte Carlo simulation of 100 trials of cohorts of 100,000 individuals. RESULTS: Ustekinumab as first-line therapy yielded the greatest QALYs (incremental effectiveness, 0.016-0.020 QALYs), resulting in 10% more patients in remission or response, and 2% fewer surgeries at 1 year, compared with other algorithms. The model was not sensitive to 25% variation in transition probabilities. CONCLUSIONS: In a simulation based on a 35-year old male patient with moderate to severe CD, we found that ustekinumab as the first-line biologic therapy yields greater QALYs at the end of 1 year than compared with use later in the CD treatment algorithm.