Impact of adherence to concomitant gastroprotective therapy on nonsteroidal-related gastroduodenal ulcer complications.

BACKGROUND & AIMS: The clinical impact of nonadherence to gastroprotective agents (GPAs) coprescribed with anti-inflammatory therapies has not been evaluated. In a large, commercial, managed-care database, we retrospectively characterized the use of GPAs among patients receiving nonselective nonsteroidal anti-inflammatory drugs (ns-NSAIDs) or cyclooxygenase-2-selective inhibitors (coxibs) and determined the impact of nonadherence on the likelihood of gastroduodenal ulcer complications. METHODS: Analyses identified the populations of patients with concomitant histamine-2 receptor antagonist or proton pump inhibitor (PPI) therapy and determined adherence with the prescribed therapy with respect to the duration of anti-inflammatory treatment. Multivariate regression analyses modeled the association between adherence with concomitant protective therapy and the likelihood of upper gastrointestinal (GI) complications including peptic ulcer disease, ulcer, and/or upper-GI bleed. RESULTS: Among 144,203 patients newly prescribed anti-inflammatory therapies, 1.8% received concomitant GPA treatment (ns-NSAIDs, 1.4% vs coxibs, 2.6%; P < .0001). The likelihood of GPA use increased with the presence of risk factors: age older than 65 years (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.3-1.5) and prior history of peptic ulcer disease (OR, 2.5; 95% CI, 1.8-3.3), esophagitis/gastroesophageal reflux (OR, 3.8; 95% CI, 3.5-4.1), ulcer/upper-GI bleed (OR, 1.4; 95% CI, 1.2-1.5), or gastritis (OR, 2.5; 95% CI, 2.2-2.8). Of patients receiving concomitant PPI therapy, 68% had adherence rates of 80% or more. A significantly higher risk of upper-GI ulcers/complications was observed in ns-NSAID patients with adherence rates of less than 80% compared with adherence rates of 80% or more (OR, 2.4; 95% CI, 1.0-5.6), but no such relationship was observed among patients who took coxibs. CONCLUSIONS: Few patients receive concomitant GPA therapy when prescribed anti-inflammatory treatment, although use increased with the presence of risk factors. Adherence to concomitant therapy is paramount to reducing GI events among ns-NSAID users and educational efforts should be undertaken to promote use of and adherence to GPA therapy among these patients.     

Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies

Background

Concerns have been raised about the risk of fractures with acid-suppressive medications, such as proton pump inhibitors and histamine₂-receptor antagonists.

Methods

This meta-analysis evaluated the association between proton pump inhibitor or histamine₂-receptor antagonist use and fractures. We performed a systematic search of published literature (1970 to October 10, 2010) in MEDLINE, EMBASE, and other sources. Ten publications reporting 11 studies were considered eligible for analysis.

Results

All studies were observational case-control or cohort studies and primarily evaluated older adults. The summary effect estimate for risk of hip fracture increased modestly among individuals taking proton pump inhibitors (relative risk [RR] 1.30, 95% confidence interval [CI], 1.19-1.43). There also was an increase in spine (RR 1.56, 95% CI, 1.31-1.85) and any-site fractures (RR 1.16, 95% CI, 1.04-1.30) among proton pump inhibitor users. These findings were similar in both men and women and after stratification by duration of use. In contrast, histamine₂-receptor antagonist use was not significantly associated with increased risk of hip fracture (RR 1.12, 95% CI, 0.97-1.30).

Conclusion

In this meta-analysis of observational studies, proton pump inhibitors modestly increased the risk of hip, spine, and any-site fractures, whereas histamine₂-receptor antagonists were not associated with fracture risk. The possibility of residual confounding cannot be excluded. Further skeletal evaluation should be considered for patients who are taking proton pump inhibitors and also at risk for osteoporotic fracture.     

Risk factors in German twins with inflammatory bowel disease: Results of a questionnaire-based survey

IntroductionEnvironmental factors may play an important role in the pathogenesis of IBD. The history of patients of the German IBD twin study was analyzed by questionnaires and interviews.MethodsRandomly selected German monozygotic (MZ) and dizygotic (DZ) twins with at least one sibling suffering from IBD (n = 512) were characterized in detail including demography, medical history and concomitant medications. Controls comprised of non-twin IBD patients (n = 392) and healthy subjects (n = 207).ResultsThe most significant variables that were associated with Crohn's disease (CD) or ulcerative colitis (UC) included living abroad before time of diagnosis (OR, 4.32; 95% CI, 1.57–13.69), high frequency of antibiotic use (MZ CD OR, 5.03; 95% CI 1.61–17.74, DZ CD OR, 7.66; 95% CI, 3.63–16.82, MZ UC OR, 3.82; 95% CI, 1.45–10.56, DZ UC OR, 3.08; CI, 1.63–5.92), high consumption of processed meat including sausage (MZ CD OR, 7.9; 95% CI, 2.15–38.12, DZ CD OR, 10.75; 95% CI, 4.82–25.55, MZ UC OR, 5.69; 95% CI, 1.89–19.48, DZ UC OR, 18.11; 95% CI, 7.34–50.85), and recall of bacterial gastrointestinal infections (MZ CD OR, 15.9; 95% CI, 4.33–77.14, DZ CD OR, 17.21; 95% CI, 4.47–112.5, MZ UC OR, 5.87; 95% CI, 1.61–28.0, DZ UC OR, 11.34; 95% CI, 4.81–29.67).ConclusionsThis study reinforced the association of life style events, in particular a specific dietary and infections history, with IBD. Alteration of gut flora or alterations of the mucosal immune system in reactivity to the flora could be an important factor to explain the relationship between life-style and disease.     

The Diagnostic Yield of Various Tests for Helicobacter pylori Infection in Patients on Acid-Reducing Drugs

The diagnostic yield of various tests for Helicobacter pylori infection in patients on acid-reducing drugs, such as proton pump inhibitors (PPI) and histamine-2 receptor blocker (H2RB), was compared. Seventy-four consecutive patients on acid-reducing drugs were enrolled: 34 (46%) were on PPIs, 20 (27%) were on H2RBs and 20 (27%) were not on medications. For those patients on PPIs, RUT and histology results from antrum were negative in 28 (82%) and 17 (50%) patients, respectively (OR: 4.7; 95% CI: 1.4–16.6; P = 0.004), while those from the corpus were negative in was 28 (82%) and 18 (53%) patients, respectively (OR: 4.4, 95% CI: 1.3–15.5; P = 0.006). For patients on H2RBs, RUT and histology results from the antrum were negative in 12 (60%) and six (30%) patients, respectively (OR: 3.5; 95% CI: 0.8–16.1; P = 0.05), while those from the corpus were negative in 12 (60%) and nine (45%) patients, respectively (OR: 1.8; 95% CI: 0.4–7.8; P = 0.342). For those patients on PPIs, the diagnostic yield of both RUT and histology was reduced from both the antrum and corpus. In these patients, PCR for H. pylori is more sensitive than RUT and histology.     

Does hemochromatosis predispose to celiac disease? A study of 29,096 celiac disease patients

Abstract

Background and aim. Case reports suggest an association between hereditary hemochromatosis (HH) and celiac disease (CD), but estimates of association are lacking. We estimated the association between HH and CD in a population-based study. Material and methods. Case–control study. We identified 29,096 individuals with biopsy-verified CD (equal to villous atrophy, Marsh stage III) through biopsy reports from all 28 pathology departments in Sweden. We then investigated the risk of a clinical diagnosis of HH in CD and in 144,522 controls matched for age, sex, county and calendar year. Conditional logistic regression was used to calculate odds ratios (ORs) for CD in patients with HH. Results. HH was seen in 30 patients with CD and in 60 matched controls. HH was hence associated with an increased risk of CD (OR = 2.30; 95% CI = 1.53–3.45). Restricting HH to individuals with at least two records of HH, the OR for CD was 2.54 (95% CI = 1.57–4.11), with a similar risk estimate when we only looked at HH diagnosed before CD (and matched date in controls) (OR = 2.64; 95% CI = 1.24–5.60). Conclusion. HH seems to be associated with an increased risk of CD.     

Effect of lansoprazole versus roxatidine on prevention of bleeding and promotion of ulcer healing after endoscopic submucosal dissection for superficial gastric neoplasia

Background  

Proton pump inhibitors have been reported to be more useful than histamine-2 receptor antagonists for the prevention of bleeding after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia. The aim of this study was to assess the effects of the proton pump inhibitor lansoprazole and the histamine-2 receptor antagonist roxatidine for the prevention of bleeding and the promotion of ulcer healing after ESD and to compare the cost-effectiveness of these two drugs.     

Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis

BackgroundPhosphodiesterase-5 inhibitors (PDE5i) have been used to treat pulmonary hypertension and right ventricular failure in patients with left ventricular assist devices (LVAD). The effects of PDE5i on post-LVAD outcomes including hemocompatibility-related adverse events are not well-established. This systematic review and meta-analysis aims to evaluate the effects of PDE5i on post-LVAD outcomes.Methods and ResultsA comprehensive literature search was conducted using Pubmed and Embase databases from inception through November 25, 2020, to compare post-LVAD outcomes in patients with or without PDE5i use. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I² statistic were calculated. Thirteen observational studies were included in this analysis. The use of PDE5i was not significantly associated with lower postoperative right ventricular failure (OR 0.38, 95% CI 0.02–5.96, P = .41). There was no significant association between PDE5i and gastrointestinal bleeding (OR 1.23, 95% CI 0.76–1.98, P = .2), overall stroke (OR 0.60, 95% CI 0.21–1.68, P = .17), ischemic stroke (OR 0.61, 95% CI 0.09–4.07, P = .38), or pump thrombosis (OR 0.71, 95% CI 0.14–3.54, P = .46).ConclusionsOur meta-analysis showed no significant association between PDE5i and post-LVAD right ventricular failure. Despite the antiplatelet effects of PDE5i, there was no significant association between PDE5i and gastrointestinal bleeding, overall stroke, ischemic stroke, or pump thrombosis. Randomized controlled studies are warranted to evaluate the net benefits or harms of PDE5i in the LVAD population.     

The long-term natural history of gastroesophageal reflux disease

INTRODUCTION: Long-term gastric acid suppression has been suggested as a means to prevent complications of reflux esophagitis. We report on the 20-year follow-up of 2,306 patients with at least two endoscopic examinations who were taking no antisecretory medication before baseline endoscopy and whose long-term treatment was determined by reflux symptoms. METHODS: From 1979 through 1998, endoscopy and biopsy were performed in the Hines Veterans Affairs Hospital endoscopy clinic by three endoscopists. Antireflux treatment was symptom-driven, and endoscopies were repeated mostly for symptomatic recurrence due to cessation of therapy. RESULTS: Of 4,633 patients undergoing endoscopy for reflux symptoms, 2,306 had at least one follow-up endoscopy and biopsy. Over a mean follow-up period of 7.6 years (range, 1-20 years), the esophageal mucosa of 67% of patients remained unchanged, that of 21% improved, and that of 11% worsened. Esophageal stricture requiring dilation developed from a normal baseline mucosa in one of 1,313 patients (0.08%) and from an erosive baseline mucosa in 18 of 957 patients (1.9%). The overall incidence of stricture in patients with gastroesophageal reflux (GER) disease was <1/1,000 per year. Nonsteroidal anti-inflammatory drug (NSAID) consumption was associated with less mucosal improvement (odds ration [OR] = 0.67; confidence interval [CI] = 0.46-0.98). Use of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was associated with mucosal improvement (OR for PPIs = 1.49; CI = 1.14-2.17). Cohn's kappa was 42%, confirming the results that demonstrate stability of esophageal mucosal disease in the majority of patients. CONCLUSIONS: Symptom-driven treatment of GER disease after a thorough endoscopic examination to exclude premalignant or malignant esophageal mucosal disease is practical and safe for the vast majority of patients with uncomplicated GER symptoms.     

Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis

BackgroundThe role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis.MethodsWe searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models.ResultsSix observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I² = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02).ConclusionsEvidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.     

A Large Cohort Study Evaluating Risk Factors Associated With Uncontrolled Hypertension

Hypertension is the most common primary diagnosis in the United States. Risks for long‐term consequences such as myocardial infarction, heart failure, stroke, and kidney disease continue to significantly increase as long as hypertension remains uncontrolled. This retrospective cohort study of 661,075 patients identified with uncontrolled hypertension, defined as systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg, from a large integrated healthcare organization was conducted to examine multiple patient characteristics to determine their association with uncontrolled hypertension. Multivariate analysis revealed that compared with Caucasians, African Americans (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.16–1.20) were significantly associated with uncontrolled hypertension, as were unpartnered populations (OR, 1.15; 95% CI, 1.14–1.17), number of antihypertensive medications prescribed (OR, 1.37; 95% CI, 1.33–1.41), and adherence to most antihypertensive medications. A secondary analysis found an association between uncontrolled blood pressure and Patient Health Questionnaire‐9 (PHQ‐9) score (OR, 1.21; 95% CI, 1.16–1.26). Our findings suggest that the presence of these identified risk factors recommends a commitment to a more aggressive hypertension management program to prevent cardiovascular disease caused by uncontrolled hypertension.     

Clinical features and natural history of idiopathic peptic ulcers: a retrospective case–control study

Abstract

Objectives: Peptic ulcer disease (PUD) is still common worldwide and is characterized by high mortality and morbidity. Following the decline of Helicobacter pylori infection, the detection of idiopathic PUD (IPUD) has become more frequent, making diagnosis and treatment more difficult. In this study, the clinical features and natural history of IPUD were analyzed.

Methods: This was a retrospective case?control study conducted in a tertiary care setting (University of Sassari, Italy). Records of 9,212 patients undergoing upper endoscopy from 2002 to 2018 were analyzed. Following the exclusion of H. pylori, NSAIDs, and unusual PUD causes, the remaining were labelled as IPUD. Cases (IPUD) and controls (PUD negative) were compared, adjusting for several covariates through multivariate logistic regression models.

Results: Among 380 PUD, 95 were considered IPUD. The proportion rose over the study period in contrast to the decline of H. pylori-PUD. Factors significantly associated with IPUD, after adjusting for all covariates, were age (OR, 3.520; 95% CI, 1.634???7.585), male sex (OR, 3.126; 95% CI, 1.888???5.176), hospitalization (OR, 2.968; 95% CI, 1.926???4.575), and number of medications (OR, 2.808; 95% CI, 1.178???6.735). A clinical history positive for PUD was the major risk associated with IPUD (OR, 3.729; 95% CI, 2.050???6.785). Patients with IPUD were treated with the highest proton pump inhibitor (PPI) dose for 40–60?days. Follow up endoscopy showed a cure rate of 97.6%.

Conclusion: The relative proportion of IPUD is increasing in our population in contrast to the drop of H. pylori-PUD. Treatment with high-dose PPI, and for a long duration, heals IPUD and protects from recurrence.     

Proton pump inhibitor discontinuation in long-term care

OBJECTIVES: To determine factors associated with proton pump inhibitor (PPI) discontinuation in long‐term care. DESIGN: Retrospective cohort analysis. SETTING: Veterans Affairs (VA) long‐term care facilities. PARTICIPANTS: Veterans admitted for nonhospice care in 2005 with a length of stay of 7 days or more who were prescribed a PPI within 7 days of admission (N=10,371). MEASUREMENTS: Prescribed medications and comorbidities were determined from VA pharmacy and administrative databases and functional status from Minimum Data Set records. Associations between participant characteristics and PPI discontinuation were determined using Cox proportional hazard ratios (HRs), censoring at death, discharge, or 180 days after admission. RESULTS: Participants were predominantly male (97%) and had a median age of 73 (interquartile range 60–81). There were 2,749 (27%) PPI discontinuations; 43% of these occurred within 28 days of admission. Hospitalizations (HR=1.22, 95% confidence interval (CI)=1.01–1.46), preadmission PPI use (HR=1.35, 95% CI=1.16–1.56), and lowest functional status (HR=1.22, 95% CI=1.03–1.45) were associated with early PPI discontinuation in adjusted models. Participants with gastric acid–related disease (HR=0.53, 95% CI 0.46–0.61), diabetes mellitus (HR=0.82, 95% CI 0.72–0.94), and those who were prescribed six or more medications (6–7 medications, HR=0.78, 95% CI=0.66–0.92; 8–10 medications, HR=0.64, 95% CI=0.54–0.76; ≥11 medications 0.51, 95% CI=0.42–0.62) were less likely to have early discontinuation. No PPI discontinuer had PPIs resumed during the study, and few (9%) had histamine‐2 receptor antagonist substitutions. CONCLUSION: Although there may be clinical uncertainty regarding PPI discontinuation, more than one‐quarter of participants prescribed a PPI upon admission to long‐term care had it discontinued within 180 days. Targeting individuals prescribed PPIs for medication appropriateness review may reduce prescribing of potentially nonindicated medications.     

The impact of acid suppression medications and non-steroidal anti-inflammatory drugs on clinical and histologic features in celiac disease

IntroductionThe prevalence of celiac disease (CD) in the US has increased in past decades, as has use of proton pump inhibitors (PPIs), histamine-2-receptor antagonists (H2RAs), aspirin (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs). We aimed to measure the association between medication use and distribution of villous flattening (VF) among newly diagnosed CD patients.MethodsWe performed a cross-sectional study of adult patients with newly-diagnosed CD at two institutions. We collected data on regular use of these medications, clinical presentation, CD serologic status, and distribution of VF. We compared current ASA/NSAID users to non-users, and current PPI/H2RA users to non-users, with regard to these clinical characteristics.ResultsOf 148 patients with newly-diagnosed CD, current users of ASA/NSAIDs were older than non-users (47 vs 39 years, p = 0.003) and users of PPI/H2RAs were older than non-users (48 vs 39 years, p = 0.004). PPI/H2RA users comprised 12% of seropositive patients, compared to 55% of seronegative patients (p < 0.01). Patient gender and distribution of villous flattening in the bulb and distal duodenum did not differ by PPI/H2RA or ASA/NSAID use.ConclusionsPPI/H2RA use was associated with seronegative CD. Given the effect of these medications on gastric milieu, the impact of these drugs on presentation and course of CD deserves further investigation.     

Increased risk of immune thrombocytopenic purpura among inpatients with coeliac disease

Objective. Case reports have indicated a link between coeliac disease (CD) and immune thrombocytopenic purpura (ITP). Two national, register-based studies were carried out to investigate a possible association between CD and ITP and vice versa. Material and methods. In a cohort study of 14,347 individuals with inpatient diagnoses of CD and 69,967 reference individuals matched for age, gender, calendar year and county, the Cox regression was used to estimate the risk of subsequent inpatient diagnoses of ITP (of any type or chronic). In a case control design, conditional logistic regression was used to assess the risk of exposure (diagnosis of ITP prior to CD) in 15,382 cases (individuals with diagnoses of CD) and 76,824 matched controls. Diagnoses of CD and ITP were identified through the Swedish National Inpatient Register. Results. Individuals with CD were at increased risk of both subsequent ITP of any type (hazard ratio (HR)=1.91; 95% CI=1.19–3.11; p=0.008) and subsequent chronic ITP (HR 2.77; 95% CI=1.09–7.04; p=0.033). Risk estimates were similar when reference individuals were restricted to inpatients. There was also a positive association between CD and prior ITP of any type (odds ratio (OR)=2.96; 95% CI=1.60–5.50; p=0.001) or with prior chronic ITP (OR=6.00; 95% CI=1.83–19.66; p=0.003). Conclusions. We found a positive association between CD and both ITP of any type and chronic ITP, irrespective of which disease came first, and suggest there should be increased awareness of CD in patients with ITP.     

Mortality and causes of death in different celiac disease phenotypes during long-term follow-up

BackgroundCeliac disease has been associated with increased mortality, but data on long-term mortality are scarce.AimsTo determine long-term mortality in celiac disease.MethodsThe study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 – 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time.ResultsDuring the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85–1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38–4.24 and HR 2.14, 95% CI 1.05–4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09–1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortalityConclusionsOverall mortality was not increased in any celiac disease phenotype during a very long-term follow-up.