Bile Acid Sequestrant Therapy in Microscopic Colitis.

GOALS: There is an unmet need in investigating corticosteroid-sparing treatments for induction and maintenance of remission in microscopic colitis (MC). The authors' aim was to evaluate the outcomes of patients with MC treated with bile acid sequestrants (BAS). BACKGROUND: MC is a common chronic diarrheal illness. Budesonide is effective induction therapy, but relapses are high after cessation of treatment. STUDY: Our cohort consisted of patients enrolled in our institutional MC registry, a biorepository of histology-confirmed diagnoses of MC. Patients receiving BAS for the treatment of MC were reviewed at each clinical visit for efficacy or ability to decrease budesonide maintenance dosing. RESULTS: The authors included 79 patients (29 collagenous colitis and 50 lymphocytic colitis) with a median follow-up period of 35 months (range, 1 to 120). Most patients were female individuals (78%) and the median age was 69 years (range, 29 to 87). BAS therapy was used in 21 patients who were budesonide-naive, with a response rate of 76% (16/21). In patients treated previously with budesonide, 46 patients were budesonide-dependent and given BAS as maintenance therapy. Of these patients, 23 (50%) were able to decrease their budesonide dosing and 9 (20%) were able to stop budesonide completely. Seven of 46 patients (15%) stopped BAS because of intolerance, perceived lack of benefit, or treatment of concomitant diarrhea illness. CONCLUSIONS: BAS may be an effective corticosteroid-sparing option in the treatment of MC and should be considered after budesonide induction. Larger controlled studies are needed to confirm the efficacy for long-term maintenance and tolerability of BAS in patients with MC.

Nonsteroidal anti-inflammatory drug exposure and the risk of microscopic colitis.

BACKGROUND: Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. METHODS: A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. RESULTS: In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p < 0.01). After controlling for age and gender, these medications remained independent predictors of MC with odds ratio for any non-steroidal anti-inflammatory drug use of 3.04 (95% CI: 1.65-5.69). No association between MC and other previously implicated medications including proton pump inhibitors and selective serotonin reuptake inhibitors was found. CONCLUSIONS: In this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

Polygenic risk score is a predictor of adenomatous polyps at screening colonoscopy.

BACKGROUND: Single nucleotide polymorphism (SNP)-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy. METHODS: We randomly selected 1769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of < 0.5, 0.5-1.5, and > 1.5 were categorized as low, average and elevated risk. RESULTS: Among 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p < 0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p < 0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend < 0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p < 0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps. CONCLUSIONS: GRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.

Predicting Progression in Barrett's Esophagus: Development and Validation of the Barrett's Esophagus Assessment of Risk Score (BEAR Score).

OBJECTIVE: To develop and validate a scoring tool capable of accurately predicting which patients with Barrett's esophagus (BE) will progress to dysplasia and/or esophageal adenocarcinoma. BACKGROUND: Endoscopic therapies have emerged capable of eradicating BE with high efficacy and low complication rates, but which patients should receive treatment is still debated. Current knowledge of risk factors is insufficient to allow for the accurate prediction of which patients will progress to dysplasia or adenocarcinoma. METHODS: We retrospectively collected data from a cohort of BE patients over a 13-year period. A multivariable logistic regression model was constructed to predict progression. A simplified risk of progression (ROP) score was developed from weighted beta coefficients. Internal validation was performed using bootstrap analysis, and model discrimination was assessed using k-fold cross-validation. RESULTS: The cohort included 2591 BE patients of which 133 progressed to dysplasia/adenocarcinoma. Multivariable analysis with bootstrap internal validation resulted in 5 variables associated with an increased ROP (age ≥70 years, male sex, lack of proton-pump inhibitor use, segment greater than 3 cm, and history of esophageal candidiasis). Using this model, we developed a simple ROP score between 0 and 8. Receiver operating characteristic analysis showed a cutoff of 3 or higher to have a sensitivity and specificity of 70% and 79%, respectively. Patients with a score of 3 or higher had an odds ratio of 9.04 (95% confidence interval 6.06-13.46). The c-statistic obtained from 10-fold cross-validation was 0.76 (95% confidence interval 0.72-0.79), indicating good overall discrimination. CONCLUSIONS: Our data show the development and internal validation of the Barrett's Esophagus Assessment of Risk Score as capable of quantifying the likelihood of progression to dysplasia/adenocarcinoma. The Barrett's Esophagus Assessment of Risk Score can be used clinically to guide treatment decisions in nondysplastic BE patients.

Screening Colonoscopy Withdrawal Time Threshold for Adequate Proximal Serrated Polyp Detection Rate.

INTRODUCTION: For adequate adenoma detection rate (ADR), guidelines recommend a mean withdrawal time (MWT) of ≥ 6 min. ADR has been shown to correlate strongly with proximal serrated polyp detection rate (PSP-DR), which is another suggested quality measure for screening colonoscopy. However, the impact of directly measured withdrawal time on PSP-DR has not been rigorously studied. We examined the relationship between MWT to ADR and PSP-DR, with the aim of identifying a functional threshold withdrawal time associated with both increased ADR and PSP-DR. METHODS: This was a retrospective study of endoscopy and pathology data from average-risk screening colonoscopy examinations performed at a large system with six endoscopy laboratories. A natural language processing tool was used to determine polyp location and histology. ADR and PSP-DR were calculated for each endoscopist. MWT was calculated from colonoscopy examinations in which no polyps were resected. RESULTS: In total, 31,558 colonoscopy examinations were performed, of which 10,196 were average-risk screening colonoscopy examinations with cecal intubation and adequate prep by 24 gastroenterologists. When assessing the statistical significance of increasing MWT by minute, the first significant time mark for PSP-DR was at 11 min at a rate of 14.2% (p = 0.01). There was a significant difference comparing aggregated MWT < 11 min compared to ≥ 11 min looking at the rates of adenomas [OR 1.65 (1.09-2.51)] and proximal serrated polyps [OR 1.81 (1.06-3.08)]. While ADR linearly correlated well with MWT (R = 0.76, p < 0.001), the linear relationship with PSP-DR was less robust (R = 0.42, p = 0.043). CONCLUSION: In this large cohort of average-risk screening colonoscopy, a MWT of 11 min resulted in a statistically significant increase in both ADR and PSP-DR. Our data suggest that a longer withdrawal time may be required to meet both quality metrics.

Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin-Associated Erosions and Ulcers.

Aspirin for secondary cardiovascular disease prevention is well established, but treatment discontinuation, often because of gastrointestinal mucosal injury or symptoms, can lead to increased risk for cardiovascular events. Proton pump inhibitor therapy is recommended for aspirin-treated patients at gastrointestinal risk. PA32540 [enteric-coated aspirin (EC-ASA) 325 mg + immediate-release omeprazole 40 mg] was compared with EC-ASA 325 mg alone once daily for 6 months in 2 duplicate, randomized double-blind trials in gastrointestinal-risk patients taking aspirin for ≥3 months for secondary prevention. In this post hoc analysis, we determined the prevalence of endoscopic upper gastrointestinal ulcers at screening and whether baseline endoscopic gastric erosions impacted subsequent ulcer development. At the screening endoscopy, 6% of subjects had upper gastrointestinal ulcers (not eligible for randomization) and 40% had gastric erosions. Conditional logistic regression modeling showed that baseline gastric erosions are significantly associated with endoscopic gastric ulcer development (OR = 2.12, 95% confidence interval, 1.26-3.57). In subjects with baseline gastric erosion, 4.2% of PA32540-treated versus 13.0% of EC-ASA-treated subjects (P = 0.001) subsequently developed endoscopic gastric ulcers. These data suggest that gastric injury predisposes to gastric ulcer development when taking EC-ASA, and exposure to immediate-release omeprazole in the presence of aspirin therapy significantly reduces the likelihood of progressing to gastric ulcers.

Reflux control is important in the management of Barrett's Esophagus: results from a retrospective 1,830 patient cohort.

BACKGROUND: It is unknown whether acid/reflux control prevents progression in Barrett's esophagus. In this study, we investigate whether medical or surgical control of reflux is associated with a decreased risk of progression to dysplasia/esophageal adenocarcinoma. METHODS: We retrospectively collected and analyzed data from a cohort of Barrett's esophagus patients participating in this single-center study comprised of all patients diagnosed with Barrett's esophagus at NorthShore University Health System hospitals and clinics over a 10-year period. Patients were followed in order to identify those progressing from Barrett's esophagus to low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. We collected information from the patient's electronic medical records regarding demographic, endoscopic findings, histological findings, smoking/alcohol history, medication use including proton-pump inhibitors, and history of bariatric and antireflux surgery. Risk-adjusted modeling was performed using multivariable logistic regression. RESULTS: This study included 1,830 total Barrett's esophagus patients, 102 of which had their Barrett's esophagus progress to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma (confirmed by biopsy) with an annual incidence rate of 1.1%. Mean follow-up period was 5.51 years (10,083 patient-years). Compared to the group that did not progress, the group that progressed was older (69.3 ± 13.7 vs. 63.9 ± 13.4 years. p < 0.001) and likely to be male (75 vs. 61%, p < 0.01). In the multivariable analysis, patients who had a history of antireflux surgery (n = 44) or proton-pump inhibitor use without surgery (n = 1,641) were found to progress at significantly lower rates than patients who did not have antireflux surgery or were not taking PPI's (OR 0.18, 95% CI 0.09-0.36). CONCLUSIONS: Reflux control was associated with decreased risk of progression to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma. These results support the use of reflux control strategies such as proton-pump inhibitor therapy or surgery in patients with non-dysplastic Barrett's esophagus for the prevention of progression to dysplasia/adenocarcinoma.

PA32540 (a coordinated-delivery tablet of enteric-coated aspirin 325 mg and immediate-release omeprazole 40 mg) versus enteric-coated aspirin 325 mg alone in subjects at risk for aspirin-associated gastric ulcers: results of two 6-month, phase 3 studies.

BACKGROUND: Discontinuations and/or interruptions in aspirin therapy for secondary cardioprotection due to upper gastrointestinal (UGI) complications or symptoms have been shown to increase the risk for subsequent cardiovascular events. PA32540 is a coordinated-delivery, combination tablet consisting of enteric-coated aspirin (EC-ASA) 325 mg and immediate-release (IR) omeprazole 40 mg. METHODS: Two identically-designed, 6-month, randomized, double-blind trials evaluated PA32540 vs. EC-ASA 325 mg in a secondary cardiovascular disease prevention population taking aspirin 325 mg daily for ≥3 months and at risk for ASA-associated gastric ulcers (GUs). The combined study population was 1049 subjects (524 randomized to PA32540, 525 to EC-ASA 325 mg). The primary endpoint was the occurrence of endoscopically-determined gastric ulceration over 6 months. Safety outcomes included the rates of major adverse cardiovascular events (MACE) and UGI symptoms. RESULTS: Significantly fewer PA32540-treated subjects (3.2%) developed endoscopic GUs vs. EC-ASA 325 mg-treated subjects (8.6%) (P < .001). Overall occurrence of MACE was low (2.1%), with no significant differences between treatments in types or incidence of MACE. PA32540-treated subjects had significantly fewer UGI symptoms (P < .001) and significantly fewer discontinuations due to pre-specified UGI adverse events (1.5% vs. 8.2%, respectively; P < .001). CONCLUSIONS: PA32540 reduced the incidence of endoscopic GUs compared to EC-ASA 325 mg, but with a similar cardiovascular event profile. Due to fewer UGI symptoms, continuation on aspirin therapy was greater in the PA32540 treatment arm.

Predicting regression of Barrett's esophagus: results from a retrospective cohort of 1342 patients.

INTRODUCTION: Barrett's esophagus (BE) is the most predictive risk factor for development of esophageal adenocarcinoma (EAC), a malignancy with the fastest increasing incidence in the US. The aim of this study was to investigate differences in exposures, demographics, and comorbidities between regressing and non-regressing patients. METHODS AND PROCEDURES: We retrospectively collected and analyzed data from a cohort of BE patients participating in a single-center study comprised of all patients diagnosed with BE over a 10-year period. We collected information from the patient's electronic medical records regarding demographic data, endoscopic findings, histological findings, exposures, and history of antireflux surgery. RESULTS: This study included 1,342 BE patients, 505 (37.6%) of which experienced regression. The regressed group was 52.3% male, while the non-regressing group was 68.3% male (p < 0.001). Mean age was 65.2 ± 12.8 and 62.0 ± 13.1 years for non-regressing and regressing patients, respectively (p < 0.001). No difference was seen in BMI between regressing and non-regressing groups (27.5 ± 5.7 vs. 27.7 ± 5.4, p = 0.52). No difference was seen between groups with respect to PPI use (93.5% non-regressing vs. 94.1% regressed patients, p = 0.70), but regressed patients were more likely to take vitamin D than non-regressing patients (34.1 vs. 42.1%, p = 0.003). Regressed patients had an average segment length of 1.48 cm (±1.58 cm), in contrast to those not regressing (3.58 ± 3.09 cm (p < 0.001)). Interestingly, one patient in the regression group progressed to dysplasia, while 101 of the non-regressing patients progressed to dysplasia/EAC, a result found to be independent of segment length on multivariate analysis (p < 0.001). CONCLUSIONS: Currently, several studies have shown risk factors that can predict progression of non-dysplastic BE, but few investigate predictors for regression. Our study reports several factors that can be used to predict patients who will regress from BE and those who likely will not, tools that will be useful in tailoring therapeutic and surveillance strategies.

Adherence to gastroprotection during cyclooxygenase 2 inhibitor treatment and the risk of upper gastrointestinal tract events: a population-based study.

OBJECTIVE: Guidelines recommend coprescription of gastroprotective agents (GPAs) in patients receiving cyclooxygenase 2 inhibitors (coxibs) who are at high risk of upper gastrointestinal (UGI) tract complications (i.e., patients with a previous complicated ulcer or with multiple risk factors). Suboptimal GPA adherence has been shown to diminish the gastroprotective effect during use of nonselective nonsteroidal antiinflammatory drugs, but little is known about the effect of GPA adherence during coxib treatment. We undertook this study to determine the association between GPA adherence and UGI tract events among patients receiving coxibs. METHODS: Using primary care data from 3 databases, we conducted a case-control study in a cohort of patients age ≥50 years who were newly starting treatment with coxibs and concomitantly taking GPAs. Patients who had a UGI tract event (bleeding or symptomatic ulcer) were matched to event-free controls for age, sex, database, and calendar date. Coxib treatment intervals were defined as consecutive coxib prescriptions with intervening gaps not exceeding the duration of the previous coxib prescription. Adherence to GPAs was calculated as the proportion of days of coxib treatment covered by a GPA prescription. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using conditional logistic regression analysis. RESULTS: The coxib plus GPA-treated cohort consisted of 14,416 coxib-treated patients who received GPAs for at least 1 day, yielding 16,442 coxib treatment intervals in which a GPA was coprescribed. Most patients were treated with coxibs for <30 days. Seventy-four patients had a UGI tract event during or shortly after a coxib treatment interval in which a GPA was coprescribed, with an incidence rate of 11.9 (95% CI 9.4-14.8) per 1,000 years of coxib treatment. The risk of UGI tract events was 1.97 (95% CI 0.84-4.60) for patients with <20% adherence to GPAs compared to patients with >80% adherence to GPAs. For every 10% decrease in GPA adherence, the risk of UGI tract events increased by 9% (OR 1.09 [95% CI 1.00-1.18]). CONCLUSION: Decreasing GPA adherence among coxib-treated patients is associated with an increased risk of UGI tract events.

Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: an observational study using three European databases.

BACKGROUND: Gastro-protective agents (GPA) are co-prescribed with non-steroidal anti-inflammatory drugs (NSAID) to lower the risk of upper gastrointestinal (UGI) events. It is unknown to what extent the protective effect is influenced by therapy adherence. AIM: To study the association between GPA adherence and UGI events among non-selective (ns) NSAID users. METHODS: The General Practice Research Database (UK 1998-2008), the Integrated Primary Care Information database (the Netherlands 1996-2007) and the Health Search/CSD Longitudinal Patient Database (Italy 2000-2007) were used. A nested case-control design was employed within a cohort of nsNSAID users aged ≥50 years, who also used a GPA. UGI event cases (UGI bleeding and/or symptomatic ulcer with/without obstruction/perforation) were matched to event-free members of the cohort for age, sex, database and calendar time. Adherence to GPA was calculated as the proportion of nsNSAID treatment days covered by a GPA prescription. Adjusted OR with 95% CI were calculated. RESULTS: The cohort consisted of 618 684 NSAID users, generating 1 107 266 nsNSAID episodes. Of these, 117 307 (10.6%) were (partly) covered by GPA, 4.9% of which with a GPA coverage <20% (non-adherence), and 68.1% with a GPA coverage >80% (full adherence). 339 patients experienced an event. Among non-adherers, the OR was 2.39 (95% CI 1.66 to 3.44) for all UGI events and 1.89 (95% CI 1.09 to 3.28) for UGI bleeding alone, compared to full adherers. CONCLUSIONS: The risk of UGI events was significantly higher in nsNSAID users with GPA non-adherence. This underlines the importance of strategies to improve GPA adherence.

Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial.

BACKGROUND: Cyclo-oxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs (NSAIDs) and non-selective NSAIDs plus a proton-pump inhibitor (PPI) have similar upper gastrointestinal outcomes, but risk of clinical outcomes across the entire gastrointestinal tract might be lower with selective drugs than with non-selective drugs. We aimed to compare risk of gastrointestinal events associated with celecoxib versus diclofenac slow release plus omeprazole. METHODS: We undertook a 6-month, double-blind, randomised trial in patients with osteoarthritis or rheumatoid arthritis at increased gastrointestinal risk at 196 centres in 32 countries or territories. Patients tested negative for Helicobacter pylori and were aged 60 years and older or 18 years and older with previous gastroduodenal ulceration. We used a computer-generated randomisation schedule to assign patients in a 1:1 ratio to receive celecoxib 200 mg twice a day or diclofenac slow release 75 mg twice a day plus omeprazole 20 mg once a day. Patients and investigators were masked to treatment allocation. The primary endpoint was a composite of clinically significant upper or lower gastrointestinal events adjudicated by an independent committee. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00141102. FINDINGS: 4484 patients were randomly allocated to treatment (2238 celecoxib; 2246 diclofenac plus omeprazole) and were included in intention-to-treat analyses. 20 (0.9%) patients receiving celecoxib and 81 (3.8%) receiving diclofenac plus omeprazole met criteria for the primary endpoint (hazard ratio 4.3, 95% CI 2.6-7.0; p<0.0001). 114 (6%) patients taking celecoxib versus 167 (8%) taking diclofenac plus omeprazole withdrew early because of gastrointestinal adverse events (p=0.0006). INTERPRETATION: Risk of clinical outcomes throughout the gastrointestinal tract was lower in patients treated with a COX-2-selective NSAID than in those receiving a non-selective NSAID plus a PPI. These findings should encourage review of approaches to reduce risk of NSAID treatment. FUNDING: Pfizer Inc.

Cost-effectiveness model of endoscopic biopsy for eosinophilic esophagitis in patients with refractory GERD.

OBJECTIVES: The population prevalence of eosinophilic esophagitis (EoE) is ~7% in adults. Current American Gastroenterology Association guidelines recommend endoscopic biopsy (Bx) in patients with symptoms of dysphagia. We conducted a cost-effectiveness model to determine if endoscopic Bx is cost effective in patients with refractory gastroesophageal reflux disease (GERD) without dysphagia. METHODS: We designed a 5-year Markov model to compare costs and quality-adjusted life years for a cohort of 35-year-old patients with GERD refractory to proton pump inhibitor (PPI) therapy. We compared upper endoscopy (EGD) with and without Bx for EoE. We modeled that patients with EoE who did not undergo initial biopsy would wait 5 years until the diagnosis would be established via a second endoscopy with biopsy. RESULTS: In patients with refractory GERD without dysphagia, endoscopic Bx for EoE was associated with an incremental cost-effectiveness ratio (ICER) of $51,420 per quality of life year (QALY). The upper endoscopy with biopsy arm cost $12,490 per patient and was associated with 4.080 QALYs, compared with EGD without Bx arm that cost $12,280 and was associated with 4.076 QALYs. The ICER was <$50,000 per QALY when the prevalence of EoE exceeded 8%, or the time of missed diagnosis was 6 years or greater. The biopsy arm was also cost effective if the QALY associated with symptomatic GERD was ≤0.93, cost of 3-month course of PPI therapy ≥$770 cost of fluticasone <$650, probability of EoE resolved on PPI ≤25%, symptom resolution on fluticasone ≥70%, cost endoscopy with biopsy ≤$520, or the cost of endoscopy without biopsy exceeded $300. CONCLUSIONS: Upper endoscopy with Bx for EoE appears to be a cost-effective approach in patients when the prevalence of EoE is 8% or greater.

GERD-related health care utilization, therapy, and reasons for transfer of GERD patients between primary care providers and gastroenterologists in a US managed care setting.

PURPOSE: Patient flow between primary care physicians and gastroenterologists in the continuum of gastroesophageal reflux disease (GERD) care is poorly understood. Using administrative claims data from a large US health plan linked with data abstracted from medical records, we examined: health care resource utilization for GERD subjects treated by primary care physicians (PCPs) and gastroenterologists (GEs), determinants of GERD subject transfer between these physician types, and reasons for GERD therapy change. RESULTS: Within a sample of 169,884 patients, 211,043 PCP-based episodes of care and 40,304 GE-based episodes of care were developed. In unadjusted comparisons, GE episodes were characterized by more endoscopic procedures, on average (50.5/100 episodes), compared with PCP episodes (6.3/100, P < 0.001). Multivariate analysis showed that patients with esophagitis had 57.3% higher odds (P < 0.01) of transfer from PCP to GE compared with patients without esophagitis; patients with esophageal stricture had 98.6% higher odds (P < 0.01) of PCP-GE transfer. Patients with endoscopy during a first GE episode had 32.2% higher odds of transfer to a PCP (P < 0.01). The principal reasons for change in GERD therapy were no change or worsening of symptoms (51.7% of PCP charts; 9.5% of GE charts) and lack of response to therapy (51.7% of PCP charts, 26.2% of GE charts). CONCLUSION: Resource utilization varies greatly based on the physician's specialty. We infer that timely transfer of GERD patients to gastroenterologists when empiric treatment is insufficient may lead to more efficient clinical management.

Hepatitis C Screening in Commercially Insured U.S. Birth-cohort Patients: Factors Associated with Testing and Effect of an EMR-based Screening Alert.

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) testing rates among U.S. birth-cohort patients have been studied extensively, limited data exists to differentiate birth-cohort screening from risk- or liver disease-based testing. This study aims to identify factors associated with HCV antibody (HCV-Ab) testing in a group of insured birth cohort patients, to determine true birth cohort testing rates, and to determine whether an electronic medical record (EMR)-driven Best Practice Alert (BPA) would improve birth cohort testing rates. METHODS: All birth-cohort outpatients between 2010 and 2015 were identified. HCV-Ab test results, clinical, and demographic variables were extracted from the EMR, and factors associated with testing were analyzed by logistic regression. True birth-cohort HCV screening rates were determined by detailed chart review for all outpatient visits during one calendar month. An automated Best Practice Alert was used to identify unscreened patients at the point of care, and to prompt HCV testing. Screening rates before and after system-wide implementation of the BPA were compared. RESULTS: The historic HCV-Ab testing rate was 11.2% (11,976/106,753). Younger age, female gender, and African American, Asian, or Hispanic ethnicity, and medical comorbidities such as chronic hemodialysis, HIV infection, and rheumatologic and psychiatric comorbidities were associated with higher testing rates. However, during the one-month sampling period, true age cohort-based testing was performed in only 69/10,089 patients (0.68%). Following the system-wide implementation of the HCV BPA, testing rates increased from 0.68% to 10.76% (P<0.0001). CONCLUSIONS: We documented low HCV-Ab testing rates in our baby boomers population. HCV testing was typically performed in the presence of known risk factors or established liver disease. The implementation of an EMR-based HCV BPA resulted in a marked increase in testing rates. Our study highlights current HCV screening gaps, and the utility of the EMR to improve screening rates and population health.

Celecoxib plus aspirin versus naproxen and lansoprazole plus aspirin: a randomized, double-blind, endoscopic trial.

BACKGROUND & AIMS: Patients requiring low-dose aspirin along with nonsteroidal anti-inflammatory drugs are at increased risk for gastrointestinal injury. This study compared the incidence of gastroduodenal ulcers in patients treated with low-dose aspirin and a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug or a nonselective nonsteroidal anti-inflammatory drug plus the proton pump inhibitor lansoprazole. METHODS: Subjects 18 years or older with osteoarthritis, without gastroduodenal ulcer or erosive esophagitis at baseline endoscopy, and a cardiovascular indication for prophylaxis low-dose (81 or 325 mg) aspirin were prescribed open-label aspirin and blindly randomized to celecoxib 200 mg/day or naproxen 500 mg twice daily plus lansoprazole 30 mg once daily. Endoscopy was performed at 12 weeks or early termination. RESULTS: One thousand forty-five subjects were randomized and received at least 1 dose of study medication, and 854 (n = 426 celecoxib, n = 428 naproxen plus lansoprazole) subjects with both baseline and final visit endoscopies were evaluable for the primary efficacy analysis. Among these subjects, the rate of endoscopically confirmed gastroduodenal ulcers was not different in the celecoxib (9.9%) and naproxen plus lansoprazole (8.9%; treatment difference [95% confidence interval], 1.0% [-2.9% to 4.9%]) groups. CONCLUSIONS: In patients with osteoarthritis taking low-dose aspirin, the use of celecoxib or naproxen plus lansoprazole resulted in similar rates of gastroduodenal ulceration.

A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity.

BACKGROUND: Carrageenan is a very common food additive in Western diets, but predictably causes inflammation in thousands of cell-based and animal experiments. OBJECTIVE: To assess the impact of carrageenan exposure on the interval to relapse in patients with ulcerative colitis in remission. METHODS: A randomized, double-blind, placebo-controlled, multicenter, clinical trial was conducted to assess if patients with ulcerative colitis in remission would have a longer interval to relapse if they followed a diet with no carrageenan. All participants were instructed in the no-carrageenan diet and were randomized to either placebo capsules or carrageenan-containing capsules. The carrageenan in the capsules was less than the average daily carrageenan intake from the diet. Relapse was defined as an increase of two or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for ulcerative colitis. Participants were followed by telephone calls every two weeks until relapse or one year of participation. The occurrence of relapse and inflammatory biomarkers were compared between the two groups. RESULTS: Twelve patients completed study questionnaires. Three patients who received carrageenan-containing capsules relapsed, and none of the patients who received placebo-containing capsules relapsed (p = 0.046, log-rank test). Laboratory tests showed increases in Interleukin-6 (p = 0.02, paired t-test, two-tailed) and fecal calprotectin (p = 0.06; paired t-test, two-tailed) between the beginning and the end of study participation in the carrageenan-exposed group, but not in the placebo-group. CONCLUSION: Carrageenan intake contributed to earlier relapse in patients with ulcerative colitis in remission. Restriction of dietary carrageenan may benefit patients with ulcerative colitis.

A multicenter, randomized, double-blind, active-comparator, placebo-controlled, parallel-group comparison of the incidence of endoscopic gastric and duodenal ulcer rates with valdecoxib or naproxen in healthy subjects aged 65 to 75 years.

BACKGROUND: Compared with nonselective NSAIDs, cyclooxygenase (COX)-2-selective inhibitors have been associated with a lower incidence of gastroduodenal ulcers (in short-term endoscopic studies) and ulcer complications (in long-term trials). OBJECTIVE: The aim of this study was to compare the effects of valdecoxib 20 mg BID and naproxen 500 mg BID, administered for 6.5 days, on the upper gastrointestinal (UGI) mucosa of healthy older subjects (aged 65-75 years) as assessed by UGI endoscopy. METHODS: In this multicenter, double-blind, active-comparator, placebo-controlled, parallel-group study, eligible subjects who were free of NSAID or COX-2-selective inhibitor use for 2 weeks and who had normal UGI mucosa (mucosal grading score of 0, based on endoscopic evaluation of both the stomach and duodenum) were randomized. Serologic testing for Helicobacter pylori antibodies was conducted at baseline. No antiulcer medications were permitted. The primary end point was the incidence of gastroduodenal ulcers (gastric or duodenal mucosal grading score of 7, as indicated by any lesion with unequivocal depth > or =3 mm in diameter) after 6.5 days of blinded treatment with valdecoxib, naproxen, or placebo. Secondary end points were incidence of gastric ulcers, duodenal ulcers, and gastroduodenal erosions/ulcers, and the incidence of > or =11 gastroduodenal erosions/ulcers. All documented adverse events were self-reported by subjects or were observed by investigators. RESULTS: Sixty-one patients were randomized to receive valdecoxib, 60 to naproxen, and 60 to placebo. Mean (SD) subject age was 68.8 (3.25) years in the valdecoxib group, 68.6 (2.76) years in the naproxen group, and 68.6 (3.14) years in the placebo group (P = NS). In the valdecoxib and naproxen groups, 47.5% and 58.3% of subjects were female, respectively, compared with 56.7% of the placebo group (P = NS). Valdecoxib and placebo were associated with significantly lower incidences of gastroduodenal ulcers than naproxen (1.6% [1 gastroduodenal ulcer/61 patients] and 1.7% [1/59], respectively, vs 22.0% [13/59]; P < 0.001). Compared with naproxen, both valdecoxib and placebo were associated with significantly lower incidences of gastric (1.6% [1/61] and 1.7% [1/59] vs 15.3% [9/59]; both, P < 0.03) and duodenal ulcers (0% [0/61] and 0% [0/59] vs 8.5% [5/59]; both,P < 0.03). In all cases, the incidence of ulcers with valdecoxib was not significantly different from placebo. Results were similar for any erosions/ulcers, and when analyzed by H pylori status. The number of adverse events was low in each group. CONCLUSION: In these healthy older subjects (aged 65-75 years), valdecoxib 20 mg BID was associated with a significantly lower rate of gastroduodenal, gastric, and duodenal ulcers than naproxen 500 mg BID, even after 6.5 days of therapy.

Long-Term Safety of a Coordinated Delivery Tablet of Enteric-Coated Aspirin 325 mg and Immediate-Release Omeprazole 40 mg for Secondary Cardiovascular Disease Prevention in Patients at GI Risk.

INTRODUCTION: In two, 6-month, randomized, double-blind Phase 3 trials, PA32540 (enteric-coated aspirin 325 mg and immediate-release omeprazole 40 mg) compared to aspirin alone was associated with fewer endoscopic gastric and duodenal ulcers in patients requiring aspirin therapy for secondary cardiovascular disease (CVD) prevention who were at risk for upper gastrointestinal (UGI) events. AIMS: In this 12-month, open-label, multicenter Phase 3 study, we evaluated the long-term cardiovascular and gastrointestinal safety of PA32540 in subjects who were taking aspirin 325 mg daily for ≥ 3 months for secondary CVD prevention and were at risk for aspirin-associated UGI events. Enrolled subjects received PA32540 once daily for up to 12 months and were assessed at baseline, month 1, month 6, and month 12. RESULTS: The overall safety population consisted of 379 subjects, and 290 subjects (76%) were on PA32540 for ≥ 348 days (12-month completers). Adverse events (AEs) caused study withdrawal in 13.5% of subjects, most commonly gastroesophageal reflux disease (1.1%). Treatment-emergent AEs occurred in 76% of the safety population (11% treatment-related) and 73% of 12-month completers (8% treatment-related). The most common treatment-related AE was dyspepsia (2%). One subject had a gastric ulcer observed on for-cause endoscopy. There were five cases of adjudicated nonfatal myocardial infarction, one nonfatal stroke, and one cardiovascular death, but none considered treatment-related. CONCLUSIONS: Long-term treatment with PA32540 once daily for up to 12 months in subjects at risk for aspirin-associated UGI events is not associated with any new or unexpected safety events.

Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic agents and are among the most commonly used classes of medications worldwide. However, their use has been associated with potentially serious dose-dependent gastrointestinal (GI) complications such as upper GI bleeding. GI complications resulting from NSAID use are among the most common drug side effects in the United States, due to the widespread use of NSAIDs. The risk of upper GI complications can occur even with short-term NSAID use, and the rate of events is linear over time with continued use. Although gastroprotective therapies are available, they are underused, and patient and physician awareness and recognition of some of the factors influencing the development of NSAID-related upper GI complications are limited. Herein, we present a case report of a patient experiencing a gastric ulcer following NSAID use and examine some of the risk factors and potential strategies for prevention of upper GI mucosal injuries and associated bleeding following NSAID use. These risk factors include advanced age, previous history of GI injury, and concurrent use of medications such as anticoagulants, aspirin, corticosteroids, and selective serotonin reuptake inhibitors. Strategies for prevention of GI injuries include anti-secretory agents, gastroprotective agents, alternative NSAID formulations, and nonpharmacologic therapies. Greater awareness of the risk factors and potential therapies for GI complications resulting from NSAID use could help improve outcomes for patients requiring NSAID treatment.