Introduction

Rosacea is a common inflammatory skin disease with multiple etiologies. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RA) are acid suppressive drugs widely used for gastrointestinal diseases, and long-term use has been reported to be associated with dysbiosis which is a potential risk for development of Rosacea. This study aimed to study association between rosacea and acid suppressants in Korean national cohort.

Aims & Methods

We used Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) data of 749,166 patients with upper gastrointestinal (GI) diseases between 2001 and 2013. Duration of acid suppressants were compared between patients with and without rosacea together with other sociodemographic characteristics and hazard ratios were estimated.

Results

Longer use of acid suppressants was significantly associated with increased risk of Rosacea. After adjustment for possible confounders, increased cumulative defined daily dose (cDDD) was significantly associated with risk of rosacea (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.20-2.00, P = 0.001). Other factors significantly associated with risk of rosacea include residing at rural area (OR, 2.58; 95% CI, 2.18-3.06, P < 0.001), greater Charlson Comorbidity Index (CCI) score (OR, 1.45; 95% CI, 1.15-1.83, P = 0.002), and comorbidities (malignancy, thyroid disease, and depression).

Conclusion

Results from our study indicate that H2RA or PPI is associated with the occurrence of rosacea among patients with GI diseases in Korean population. The risk was increased in dose-response trend, even after adjusting for confounding variables. Clinicians should be aware of risks associated with prolonged use of acid suppressive drugs.

Introduction

Recent research from the Netherlands, the United States, and Korea suggests that individuals who receive a positive result on the fecal immunochemical test (FIT) may be at a higher risk of developing gastroesophageal cancer (GEC) within the following 36 months. However, the associations reported in these studies may be biased due to differences in age and sex between the FIT-positive and FIT-negative groups and other confounding factors.

Aims & Methods

We aimed to evaluate the association between FIT results and the risk of GEC in a matched cohort by age and sex. Additionally, we assessed the cost-effectiveness of a one-time Esophago-Gastro-Duodenoscopy (EGD) for individuals with positive FIT results.. We created a matched cohort of individuals aged 50 to 75 who underwent FIT testing at Clalit Health in Israel between June 2016 and June 2019. For each FIT-positive individual, we matched three FIT-negative individuals based on age, sex, and H. pylori status. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized to evaluate the association between a positive FIT result and the risk of GEC within 36 months. We calculated the incremental cost-effectiveness ratio (ICER) for a one-time EGD at $400 in individuals who tested positive for FIT. Screening is considered cost-effective if the ICER is below $50,000.

Results

The primary cohort included 483,710 individuals, while the matched cohort comprised 151,500 individuals (47.6% female, median age 62.5 years). During the follow-up period, 202 cases of GEC occurred: 0.2% (64/38,575) among FIT-positive individuals and 0.1% (138/112,925) among FIT-negative individuals, adjusted HR 1.39 (95% CI 1.03-1.87). Age, male sex, H. pylori exposure, country of birth, proton-pump inhibitor usage, smoking status, and anemia were all significantly associated with an increased risk of gastric cancer. A one-time EGD has been determined to be a cost-effective option in a range of ages and rates of localized disease at the time of EGD.

Conclusion

This matched cohort study suggests that individuals with a positive FIT may have an increased risk of GEC, which occurs at an overall rate of 0.2% within 36 months. A one-time EGD priced at $400 can be cost-effective in many scenarios.

Disclosure

NONE

Introduction

Psoriasis is a common inflammatory skin disorder following non-specific triggers such as scratching, piercing, sunburn, and chemical irritants. Involvement of immune system is widely accepted for pathogenesis studies have demonstrated importance of gut microbiota in pathogenesis of inflammatory skin diseases. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RA) are acid suppressing drugs widely used for gastrointestinal diseases, and long-term use has been reported to be associated with altered gut microbiota. This study aimed to investigate association between psoriasis and acid suppressing drugs in Korean population.

Aims & Methods

We used Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) data of 746,816 patients with upper gastrointestinal (GI) diseases between 2002 and 2013. Duration of acid suppressing drug exposure and other socio-demographic characteristics were compared between patients with and without psoriasis, and hazard ratios were estimated.

Results

Significantly larger number of patients with exposure to acid suppressing drugs had developed psoriasis compared to control cohort (46.3% vs. 33.7% respectively, P < 0.001). In the multivariate analysis, longer use of acid suppressing drugs and greater Charlson comorbidity index score were significantly associated with increased risk of psoriasis with an adjusted odds ratio, 1.89 (95% confidence interval, 1.66-2.17, P < 0.001) and 1.33 (1.17-1.51, P = <0.001), respectively.

Conclusion

Results from our study indicate that prolonged use of H2RA or PPI is associated with the risk of psoriasis among patients with GI diseases in Korean population. The risk was increased in dose-response trend, even after adjusting for confounding variables. Clinicians should be aware of risks associated with prolonged use of acid suppressing drugs.

References

1. Buhas MC, Gavrilas LI, Candrea R, Catinean A, Mocan A, Miere D, et al. Gut Microbiota in Psoriasis. Nutrients 2022;14(14).
2. Schon MP, Boehncke WH. Psoriasis. N Engl J Med 2005;352(18):1899-912.
3. Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94.
4. Nickoloff BJ, Qin JZ, Nestle FO. Immunopathogenesis of psoriasis. Clin Rev Allergy Immunol 2007;33(1-2):45-56.
5. Sabat R, Philipp S, Hoflich C, Kreutzer S, Wallace E, Asadullah K, et al. Immunopathogenesis of psoriasis. Exp Dermatol 2007;16(10):779-98.

Introduction

Patients who have gastroesophageal reflux disease(GERD) on maintenance therapy with acid-secretion inhibition drugs, it is not clear what background factors allow patients to discontinue the drugs.
This study aimed to examine the relationship of the changes in the frequency and severity of gastrointestinal symptoms after discontinuation of acid-secretion inhibitors for erosive GERD (eGERD) with possible patient background factors and to identify factors that influence these changes.

Aims & Methods

This study was a multicenter, open-label, interventional, exploratory study. eGERD patients with mild mucosal injury whose symptoms were under control and who were on maintenance therapy with acid-secretion inhibition drugs were withdrawn from the drug treatment for 4 weeks. We examined the relationship of patient backgrounds (sex, age, body mass index, alcohol consumption, smoking habits), esophageal hiatal hernia, Helicobacter pylori infection, pepsinogen I and II concentrations and I/II ratios, blood gastrin levels before and after drug discontinuation with total score change in Frequency Scale for the Symptoms of GERD (FSSG).

Results

Of the 92 patients whose symptoms could be evaluated before and after withdrawal, 66 patients (71.7% of the total) had an FSSG <8 and did not have a recurrence of symptoms after withdrawal. In addition, background factors that might be associated with recurrence or non-recurrence of patient symptoms were examined, but no associated factors were detected. Maintenance medications prior to discontinuation in the above 92 patients were proton pump inhibitors (PPIs) and vonoprazan (VPZ, a potassium ion-competitive acid blocker); PPIs and VPZ were given incidentally but in approximately equal numbers, so additional patient relationships were examined.

Conclusion

There were no patient factors that are likely to affect the discontinuation of maintenance therapy for eGERD. There was no significant difference in the extent of disease or frequency of recurrence during the discontinuation period, regardless of whether the drug before discontinuation was PPIs or VPZ. Since 70% of patients did not experience recurrence for at least 4 weeks and there were no serious complications even in patients experiencing recurrence, temporary discontinuation of maintenance therapy with ASIDs, especially with PPIs, is acceptable for mild eGERD.

Introduction

Direct oral anticoagulants (DOACs), particularly rivaroxaban and apixaban, are increasingly utilized to manage thromboembolic conditions due to their favorable efficacy and safety profiles. However, gastrointestinal bleeding (GIB) remains a significant concern associated with these medications, particularly considering pharmacogenetic variations among populations. This study aims to evaluate the frequency and identify risk factors associated with GIB in patients using rivaroxaban and apixaban in a Mexican healthcare setting.

Aims & Methods

This retrospective observational study analyzed data from January 2018 to December 2023 at the Centro Médico Nacional 20 de Noviembre, Mexico City. The cohort consisted of 278 patients: 136 on DOAC therapy (rivaroxaban or apixaban) and 142 controls without anticoagulation. Clinical data, demographic characteristics, comorbidities, and concomitant medications were systematically reviewed. Statistical methods employed included chi-square tests, Student's t-tests, and logistic regression analysis to assess the risk factors and association between anticoagulant type and incidence of GIB.

Results

The study population had a mean age of 67.36 ± 15.05 years, with an equal gender distribution (52.9% male). Rivaroxaban was significantly linked to increased GIB-related hospitalizations compared to controls (OR 1.29, 95% CI: 1.10–1.52, p < 0.001), while apixaban showed no statistically significant increase. NSAID co-administration dramatically raised the risk of GIB in rivaroxaban users (OR 16.1, 95% CI: 1.22–212.6, p = 0.03). Patients treated with DOACs experienced more hospitalizations (average 0.49 ± 0.80) and longer hospital stays (2.19 ± 3.54 days) compared to controls (0.30 ± 0.62 hospitalizations, 0.99 ± 2.68 days, respectively). Mortality rates were not significantly different between groups.

Conclusion

Rivaroxaban and apixaban present similar overall risks of gastrointestinal bleeding, although rivaroxaban is associated with higher hospitalization rates. Concomitant NSAID use substantially elevates the risk in patients on rivaroxaban. This underscores the necessity of individualized anticoagulant management strategies, especially in populations with distinct genetic and clinical characteristics, such as the Mexican demographic.

References

1. Lopes RD, Guimarães PO, Kolls BJ, et al. Gastrointestinal bleeding with novel oral anticoagulants: A systematic review and meta-analysis. BMJ. 2015;350:h1857.
2. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.
3. Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.

Introduction

The use of proton pump inhibitors (PPIs) has increased in many Western countries over the past decades. This may reflect the increasing prevalence of symptoms of gastroesophageal reflux disease (GERD) and prophylactic PPI use against gastroduodenal ulcers and haemorrhage induced by non-steroid anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid. However, increasing PPI use against functional or uninvestigated dyspepsia and other inappropriate prescription have previously been documented and may also have contributed to the observed increase in PPI use. In this study we describe the change in incident and prevalent PPI use over time and the indication for prescription.

Aims & Methods

Nationwide data were retrieved from the Norwegian Prescription Database (NorPD) and consisted of information about dispensed prescription drugs. The study population consisted of all adults with at least one PPI prescription during the study period from 2009 to 2022. PPIs were defined by their ATC codes A02BC01 – C05 in addition to M01AE52, which is an esomeprazole and naproxen combination product. Prevalent PPI use was defined as the period covered by the defined daily doses (DDD) in each prescription. The indications for prescription were defined by ICPC or ICD-10 codes depending on whether PPI was prescribed in primary care or secondary health care. National data from the Norwegian Patient Registry (NPR) on all upper endoscopies performed during the study period were combined with NorPD data and it was assessed whether incident PPI users, defined as no PPI dispensal for two years, had undergone an upper endoscopy 180 days before or after incident PPI use.

Results

The use of PPI increased from 58.1 mill DDD in 2009 to 166.9 mill DDD in 2022, i.e. 15700 DDD/1000 and 38700 DDD/1000 persons. The absolute increase in DDDs was driven by a 3.5-fold increase in esomeprazole and a 5-fold increase in the use of pantoprazole.
The prevalence of PPI use increased from 3.5% in 2009 to 9.9% in 2022. The incidence of PPI use increased from 2.85% in 2011 to 5.42% in 2022.
In 2009 the dominant indications in primary and secondary health care, respectively, were esophageal disease and GERD (72.5% and 10.7% of DDDs), gastric ulcer (3.3% and 0.46% of DDDs), duodenal ulcer (0.86% and 0.21% of DDDs), while prescriptions with no reimbursement diagnosis constituted 10.2% of DDDs. In 2022 the dominant indications were esophageal disease and GERD (57.6% and 4.7% of DDDs), musculoskeletal disorders and pain (7.1% and 0.39% of DDDs and in combination with naproxen), prophylaxis against gastroduodenal ulcer (4.8% and 0.95% DDDs), while prescriptions with no reimbursement diagnosis constituted 5.2% of the DDDs.
There were 2.27 mill cases of incident PPI use in the study period and the proportion of PPI users that underwent upper endoscopy around treatment start decreased from 25.3% in 2009 to 11.1% in 2022. In patients with esophageal disease or GERD combined the proportion examined by upper endoscopy fell from 41.4% to 27.1%, while in patients without a reimbursement diagnosis the proportion fell from 19.2% to 6.9%.

Conclusion

In this nationwide study a 2.8-fold increase in prevalent PPI use was observed during the 14-year study period. This was caused by an absolute increase in PPI use against esophageal disease and GERD as well as prophylaxis in patients given ulcerogenic comedication. The proportion of incident PPI use investigated by upper endoscopy was halved.

Introduction

Functional dyspepsia (FD) is a disorder of gut-brain interaction (DGBI) characterized by postprandial fullness, early satiation, epigastric pain or burning in the absence of a readily identifiable cause at upper endoscopy. Proton pump inhibitors (PPIs) are often used as a first-line treatment for FD, although their efficacy has not been convincingly established.

Aims & Methods

The aim was to investigate symptom patterns in FD patients with and without acid-suppressive therapy (PPI or H2-antagonist, H2RA) and to evaluate the use of these drugs in different patient groups. Ambulatory tertiary-care patients referred for upper gastrointestinal endoscopy were requested to fill out Rome IV gastro-duodenal questionnaires. Those fulfilling Rome IV FD criteria with a negative endoscopy were identified as FD patients and subdivided into patients on and off acid-suppressive therapy. The pattern of GI symptoms was compared between these two subgroups, using frequency thresholds from the Rome IV criteria. The chi-square or Fisher exact (when applicable) test was used to evaluate statistical significance (p<0.05).

Results

The Rome IV questionnaire was filled out by a total of 1002 patients (58% females, 48.5 ± 0.5 years, BMI 25.4± 0.5). Of these, 229 (23%, 73% females, 45.5 ± 1.1 years, BMI 23.9 ± 0.3) fulfilled the diagnostic criteria for FD. Organic findings at endoscopy included Barrett’s oesophagus (n=40, 4%), peptic ulcers (n=24, 2%), and reflux oesophagitis (n=352, 35%).
PPI/H2RA usage in FD patients was 60%, which was not significantly different from patients diagnosed with Barrett’s oesophagus (75%, p=0.07), peptic ulcer (50%, p=0.33), reflux oesophagitis (57%, p= 0.45) or the combined group with organic abnormality at upper endoscopy (46%, p=0.1). There was no significant difference (p=0.67) in PPI/H2RA usage between the EPS (epigastric pain syndrome, 55% usage) and PDS (postprandial distress syndrome, 50% usage) subgroups of FD.
The most prevalent symptoms in FD patients were postprandial fullness (76%), epigastric pain (67%) and bloating (62%). Patients on acid-suppressive therapy reported more nausea (41% vs 27%, p=0.04) and excessive belching (50% vs 36%, p=0.05) compared to patients without acid suppression. There was no significant difference in postprandial fullness (84% vs 73%, p=0.05), epigastric pain (75% vs 64%, p=0.08), heartburn (17% vs 28%, p=0.06) and bloating (70% vs 58%, p=0.06) between the two subgroups. Looking at the EPS and PDS subgroups of FD, there was a significant difference (p=0.03) in bloating between patients on (73%) and off (46%) acid suppression in the PDS subgroup of FD.

Conclusion

The cardinal symptom pattern in FD patients referred for upper endoscopy is similar for those on and off acid-suppressive therapy, but those on PPI/H2RA report more nausea and belching. No difference in acid-suppressive therapy use was observed between FD patients and those with organic findings at endoscopy.