Combination Of Proton Pump Inhibitor Research Articles

Children with eosinophilic esophagitis non-responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile.

A combination of proton-pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non-responders (EoE-PPI-TSnr; n = 7) and responders (EoE-PPI-TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. In all, 3164 upregulated and 3154 downregulated genes distinguished EoE-PPI-TSnr from EoE-PPI-TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE-PPI-TSnr. There was a 56% overlap in dysregulated genes between EoE-PPI-TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic-erythroid progenitors, and T helper type 1 cells were significantly higher in EoE-PPI-TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE-PPI-TSnr and correlated with the key pathways. Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.

Minimum Effective Duration of Laryngopharyngeal Reflux Disease Treatment: A Prospective Study.

To investigate the minimum therapeutic duration for patients with primary laryngopharyngeal reflux disease (LPRD) through the evaluation of symptom changes at multiple time points. Prospective uncontrolled. University medical center. Patients with LPRD at the 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring were recruited from the European Reflux Clinic. Depending on the type of LPRD, patients were treated with a combination of proton-pump inhibitors, alginate, or magaldrate. Symptoms were evaluated with the reflux symptom score (RSS) at baseline and throughout treatment (1-, 3-, 6-, and 9-month posttreatment). The most appropriate therapeutic duration was determined using the RSS changes. Signs were evaluated with the reflux sign assessment. A total of 159 patients completed the study. The mean age was 49.9 ± 15.7 years. At 1-month posttreatment, 97 patients (61.0%) were considered as early responders to treatment, and the treatment was stopped for 52 patients (32.7%). Of the 62 early nonresponders, 34 patients (21.4%) reached responded to treatment after 3 to 9 months. The cumulative therapeutic success rate at 1-month posttreatment (61.0%) progressively increased to reach a range of 82.4% to 99.3% at 9-month posttreatment. The RSS mainly decreased in the first month of treatment in early responders. In early nonresponders, RSS progressively decreased throughout the 9-month treatment period. The baseline severity of RSS is a strong predictor of therapeutic response. A therapeutic regimen of 1 month can be sufficient to treat one third of LPRD patients. The early nonresponders may require 3 to 9 months of treatment.

Pill Esophagitis: Clinical and Endoscopic Profile

Abstract Background Medications can rarely cause esophageal injury and present with acute symptoms. Multiple factors, including the type of medication, comorbidity, and method of ingestion play a role in causing drug-induced or pill esophagitis (PE). We analyzed the clinical, endoscopic, and histopathological profiles of PE cases at our gastroenterology outpatient clinic. Methods Medical records of PE cases were reviewed retrospectively over a period of 5 years at a tertiary care hospital in India from May 2017 to May 2022. The data were collected and analyzed using descriptive statistical analysis. Results A total of 30 patients diagnosed with PE were involved in the study. A slight male preponderance of 56.7% was noted with a mean age of 40.7 years. Odynophagia was the dominant symptom (70%) with a mean duration of symptoms of 5.63 days. The most common location was at the mid-esophagus (80%) followed by the lower esophagus (10%). The majority (56.7%; 17/30) had over-the-counter (OTC) drug consumption, followed by doxycycline (33.3%; 10/30). Kissing ulcers were seen in 30% of the subjects; 90% of the patients received a combination of proton pump inhibitors and sucralfate suspension for 2 weeks along with discontinuation of the causative drug, with a 96.7% resolution rate. Conclusion OTC medication and antibiotics such as doxycycline are the leading cause of PE. Prompt recognition and discontinuation of the causative drug are crucial in preventing complications. Patient education is vital in preventing PE regarding the usage of OTC medicines in developing countries.

Dissolution rates of various brands of proton pump inhibitors in combination with domperidone: an in vitro study

Background: Drug solubility, bioavailability, and dissolution rates are important in establishing in vivo efficacy. Eight brands of domperidone proton pump inhibitor combination drugs were compared to enable physicians to take an informed decision regarding the dissolution rates of various domperidone-PPI combinations available in the Indian market to allow identification and prescription of the drug with better bioavailability. Methods: The in vitro dissolution rate of a combination of domperidone-PPI drugs was measured using the United States Pharmacopeia dissolution paddle apparatus. Each flask of the dissolving testing apparatus contained one tablet and 900 mL of the media, which was dissolved in pure water with 1% Tween® stored at 37.4°C. At regular intervals, aliquots were removed, filtered, and the amount of drug released was measured. The cumulative drug release was calculated using a standard formula. Results: P04 and P07 had the fastest and the slowest onsets of action, respectively. P01 (Omez DSR) and P08 exhibited the longest and the shortest durations of action, respectively. The P05, P06, and P08 formulations had greater particulate matter than the other formulations. Under in vitro conditions, the bioavailability of Omez DSR was nearly two-fold higher than P07 and five-fold higher than P08. Conclusions: Although P04 exhibited the fastest onset of action, Omez DSR had the longest duration of action, superior bioavailability, and ensured the rapid and continuous release of domperidone. Omez DSR demonstrated superior properties compared with other brands.

SAT-325 - Outcome of sucralfate vs proton pump inhibitor vs sucralfate and proton pump inhibitor combination post endoscopic esophageal variceal band ligation-A randomized controlled trial

SAT-325 - Outcome of sucralfate vs proton pump inhibitor vs sucralfate and proton pump inhibitor combination post endoscopic esophageal variceal band ligation-A randomized controlled trial

An ecofriendly multi-analyte high performance thin layer chromatographic densitometric determination of amoxicillin, metronidazole, and famotidine in their ternary mixtures and simulated gastric juice: A promising protocol for eradicating Helicobacter pylori.

Gastrointestinal tract disorders constitute a heavy burden to healthcare providers.To eradicate Helicobacter pylori infection, different triple therapy protocols have been proposed. Among which are combinations of proton pump inhibitors (e.g. omeprazole), histamine-2 receptor antagonists (e.g. famotidine), along with antibiotics (e.g. amoxicillin). In this work, a sensitive and accurate high performance thin layer chromatographic method was developed for the simultaneous determination of amoxicillin, metronidazole, and famotidine in bulk powder and laboratory prepared combined-tablet mixtures. Complete separation of the cited compounds was achieved using pre-coated silica gel plates with a mixture of methanol: chloroform: toluene: water: glacial acetic acid (5:2:1.5:0.5:0.1 v/v/v/v/v) as the mobile phase. The method was fully validated as per the international conference of harmonization guidelines. Good linearity, correlation coefficient of 0.9991, was obtained in the concentration ranges 0.1-1.6 μg band-1 (amoxicillin), 0.1-0.9 μg band-1 (metronidazole) and 0.1-0.9 μg band-1 (famotidine). Since the method allowed the determination of the three compounds in combined tablets with high degree of selectivity, accuracy, precision, with cost-effectiveness, it could be used for regular quality control. Moreover, the applicability of the proposed method was extended to the determination of the ternary mixture in simulated gastric juice. Method greenness was assessed using different green metrics. This article is protected by copyright. All rights reserved.

DRUG INDUCED HYPER PROLACTINEMIA: INTERESTING OBSERVATIONS.

Introduction: Drugs are a common cause of hyperprolactinemia. It is essential to differentiate this cause from other pathological causes which avoids unnecessary investigations.Thorough history will help us in finding the responsible drug and holding the same will be rewarding. Here we are reporting such cases of drug induced hyperprolactinemia. Methods: It was a cross-sectional observational study. Subjects were recruited from our outpatient department. Hyperprolactinemia was defined as blood prolactin levels >30 ng/mL in females and >24 ng/mL in males, regardless of the presence of symptoms.Serum prolactin was repeated one week after holding the suspected drug(s).Drug induced hyperprolactinemia defined,if holding of responsible drug made normalization of prolactin levels.Results: Total of 32 subjects were studied in this study with age of 35.5±10.8years.Predominantly female subjects were present with female to male ratio 5.4. Basal prolactin was 132±68.7ng/mL and after holding the drug prolactin value was 16.9±8.2. Proton pump inhibitors in combination with prokinetics were the leading cause (71.8%) and followed by multiple drug combinations (15.6%), anti-psychiatric drugs (9.3%) and oral contraceptives (3.1%). The mean prolactin in the combination of levosulpride was 176 ng/dl, whereas with domperidone it was 126 ng/dl & with oral contraceptives, respiridone it was 134,151ng/dl respectively.Conclusion: Majority cases were clinically symptomatic. Among female subjects commonest presentation was galactorrhea followed by irregular menses and breast heaviness and men presented with erectile dysfunction.Contrary to common belief in our study PPI with prokinetic combination is the most common offending agent than anti-psychotic agents. Levosulpride being the most potent drug in inducing hyper prolactinemia than other agents, though the popular belief was with the Risperidone. As the utility of PPI prokinetic combination is increasing, this might replace anti-psychotic agents as most potent & most common etiology for drug induced hyper prolactinemia.

Acute, Recurrent, and Chronic Laryngopharyngeal Reflux: The IFOS Classification.

To investigate the clinical patterns and disease evolution of laryngopharyngeal reflux (LPR) patients. Patients with LPR diagnosed by hypopharyngeal-esophageal impedance-pH monitoring were prospectively followed in three medical centers. Symptoms and findings were assessed with reflux symptom score (RSS) and reflux sign assessment (RSA). Patients were treated with 3-to 9-month diet and combination of proton pump inhibitors, alginate or magaldrate. Patients were followed for 3 years to determine the clinical evolution of symptoms over time. LPR that did not recur was defined as acute. Recurrent LPR consisted of reflux with one or several recurrences yearly despite successful treatment. Chronic LPR was reflux with a chronic course of symptoms. Predictive indicators of clinical evolution were investigated. One hundred forty patients and 82 healthy individuals completed the evaluations. Among patients, 41 (29.3%), 57 (40.7%), and 42 (30.0%) had acute, recurrent, or chronic LPR respectively. Baseline quality of life-RSS (QoL-RSS) and RSS total scores were significantly higher in chronic LPR patients. The post-treatment decrease of QoL-RSS and RSS of acute LPR patients were significantly faster as compared to recurrent and chronic patients. QoL-RSS >5 reported adequate sensitivity (94.2) and specificity (75.3). QoL-RSS thresholds defined acute (QoL-RSS=6-25), recurrent (QoL-RSS=26-38), and chronic (QoL-RSS > 38) LPR. Baseline QoL-RSS may predict the clinical course of LPR patients: acute, recurrent, or chronic. A novel classification system that groups patients according to the longevity, severity, and therapeutic response of symptoms was proposed: the International Federation of Otorhinolaryngological Societies Classification of LPR. 3 Laryngoscope, 133:1073-1080, 2023.

Development of Risk Prediction Model for Grade 2 or Higher Hypocalcemia in Patients With Bone Metastasis Treated With Denosumab Plus Cholecalciferol (Vitamin D3 )/Calcium Supplement.

Denosumab-induced hypocalcemia is sometimes severe, and although a natural vitamin D/calcium combination is used to prevent hypocalcemia, some patients rapidly develop severe hypocalcemia even under supplementation. It is clinically important to predict this risk. This study aimed to develop a risk prediction model for grade ≥2 hypocalcemia within 28 days after the first denosumab dose under natural vitamin D/calcium supplementation. Using a large database containing multicenter practice data, 2399 patients with bone metastasis who were treated with denosumab between June 2013 and May 2020 were retrospectively analyzed. Background factors in patients who developed grade ≥2 hypocalcemia within 28 days after the first denosumab dose and those who did not were compared by univariate analysis. Multivariate analysis was conducted to develop a risk prediction model. The model was evaluated for discriminant performance (receiver operating characteristic-area under the curve, sensitivity, specificity) and predictive performance (calibration slope). A total of 124 patients in the hypocalcemia group and 1191 patients in the nonhypocalcemia group were extracted. A risk prediction model consisting of sex, calcium, albumin, alkaline phosphatase, osteoporosis, breast cancer, gastric cancer, proton pump inhibitor combination, and pretreatment with zoledronic acid was developed. The receiver operating characteristic-area under the curve was 0.87. Sensitivity and specificity were 83% and 81%, respectively, and the calibration slope indicated acceptable agreement between observed and predicted risk. This model appears to be useful to predict the risk of denosumab-induced hypocalcemia and thus should be helpful for risk management of denosumab treatment in patients with bone metastases.

Combination of Proton Pump Inhibitors and Food Elimination Diet for Eosinophilic Esophagitis Refractory to Monotherapy.

Eosinophilic esophagitis (EoE) is an antigen-mediated inflammatory esophageal disease that is commonly treated with high-dose proton-pump inhibitors (PPIs), topical corticosteroids, or food elimination diet (FED) monotherapy. Combination treatment has not been well studied in the management of EoE. We aimed to determine if PPI and FED combination therapy was able to induce histologic remission in patients with EoE refractory to monotherapy. We conducted a retrospective cohort study identifying patients with EoE that was refractory to PPI monotherapy and FED monotherapy but histologically responsive to PPI and FED combination therapy. We also identified symptom changes through chart review. Out of 405 EoE patients, 12 patients were identified with EoE that was refractory to PPI monotherapy and FED monotherapy but histologically responsive to PPI and FED combination therapy. Out of 12 patients, 11 (91.67%) noted resolution of symptoms while on combination therapy. Comparative analysis of peak eosinophil counts showed that patients achieved a median of 4.5 eos/hpf (interquartile range [IQR], 2-6.5), which was significantly decreased compared to baseline (median, 45; IQR, 35.5-50; Wilcoxon signed-rank test, P < .001), PPI monotherapy (median, 41; IQR, 26-50; Wilcoxon signed-rank test, P < .001), and FED monotherapy (median, 45; IQR, 17-67.5; Wilcoxon signed-rank test, P < .001). Our work shows that patients with EoE refractory to PPI monotherapy and FED monotherapy can successfully achieve histologic remission and symptom benefit with PPI and FED combination therapy. Therefore, combination therapy should be considered a viable option for patients with EoE who fail treatment with first-line monotherapies.

Ребамипид и ингибиторы протонной помпы: преимущества совместного применения

The article describes the benefits of rebamipide and proton pump inhibitors combination therapy for acid-related diseases. It was shown that rebamipide have a positive effect on various parts of the protective barrier of the epithelium in gastroesophageal reflux disease, chronic gastritis, peptic ulcer disease, functional dyspepsia, NSAID-induced gastrointestinal erosive and ulcerative lesions, and in the treatment of Helicobacter pylori infection. Key words: gastroesophageal reflux disease, proton pump inhibitors, NSAID gastropathy, rebamipide, functional dyspepsia, peptic ulcer disease, Helicobacter pylori

Helicobacter Pylori Eradication Therapy: Still a Challenge.

IntroductionHelicobacter pylori (H. pylori) infection is prevalent worldwide. H. pylori therapies' adverse effects can contribute to noncompliance among patients. This study aimed to assess the association between compliance to H. pylori eradication therapy and adverse effects using various drug regimens.MethodWe conducted an observational study from September 2017 to February 2020 in two tertiary care hospitals in patients with dyspeptic symptoms. H. Pylori detection was done by histopathological examination of gastric mucosa during upper gastrointestinal endoscopy or stool for H. pylori antigen. Patients with positive results were randomly assigned one of the nine different regimens consisting of a combination of proton pump inhibitors along with at least two antibiotics. The antibiotics used in different combinations were amoxicillin, clarithromycin, metronidazole, doxycycline, levofloxacin, and bismuth sulfate. The treatment groups received standard triple therapy with and without probiotics, sequential, concomitant, levofloxacin-based triple therapy, or sequential and bismuth-based quadruple treatments. All treatments were given for two weeks. At the end of the treatment period, patients were interviewed about completing treatment and any adverse effects they may have experienced during therapy. Data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp.).ResultsA total of 250 patients were included in the study (62% males, 38% females) with a mean age of 37 years ± 13 years (range 12-84 years). Most patients completed the treatment regimen (80.4%), and 19.6% did not complete treatment because of adverse effects (p<0.005). The levofloxacin-based, concomitant, and standard triple regimen with probiotic treatments had the highest tolerance (≥85%). Common adverse effects were abdominal and epigastric pain (11%), alteration of taste, and diarrhea (6.5%).ConclusionH. pylori eradication therapy is always a challenge. Patient compliance to the treatment can only be ensured by medicines with fewer adverse effects. In our study, levofloxacin-based triple, concomitant, and standard triple regimens with probiotics are maximally acceptable treatments.

Drug Induced Hyperprolactinemia

Introduction: Drugs are a common cause of hyperprolactinemia. It is essential to differentiate this cause from other pathological causes which avoids unnecessary investigations. Detailed history will help us in identifying the responsible drug and withdrawing the same will be rewarding. Here we are reporting a case series of drug induced hyperprolactinemia. Methods: It was a cross-sectional observational study. Subjects were recruited from our outpatient department. Hyperprolactinemia was defined as blood prolactin levels >30 ng/mL in females and >24 ng/mL in males, regardless of the presence of symptoms. Serum prolactin was repeated one week after holding the suspected drug(s). Drug induced hyperprolactinemia is defined as normalisation of serum prolactin on discontinuation of the offending drug. Demographics, clinical presentation and offending drug name were entered in pre designed proforma.Results: Total of 32 subjects were studied in this study with age of 35.5±10.8years. Predominantly female subjects were present with female to male ratio 5.4. Basal prolactin was 132±68.7ng/mL and after holding the drug prolactin value was 16.9±8.2. Proton pump inhibitors in combination with prokinetics were the leading cause (71.8%) and followed by multiple drug combinations (15.6%), anti-psychiatric drugs(9.3%) and oral contraceptives(3.1%). Overall 86.75% of subjects were having symptomatic presentation. Commonest clinical presentation among the women was galactorrhea (88.9% of female subjects) followed by irregular menstrual cycles (59% of female subjects) and breast heaviness in 29.6%. Among the men erectile dysfunction was common presentation, noted among 80% of them. Asymptomatic presentation was there in 6.25% of subjects. All subjects were improved clinically after withdrawal of the the offending drug(s).Conclusions: Most of the subjects were clinically symptomatic. Most common symptom in female was galactorrhea followed by irregular menses and breast heaviness, and erectile dysfunction in males. All subjects were improved clinically after withdrawal of the offending drug(s). A detailed drug history is rewarding and avoids unnecessary investigations for hyperprolactinemia

Antichelicobacter therapy in the context of increasing bacterial resistance

A modern strategy for the treatment of diseases associated with Helicobacter pylori is the mandatory inclusion in the scheme of treatment of antibiotics, as well as considering the level of bacterial resistance to the main components of therapy. In Ukraine, Helicobacter pylori infection in some areas can reach about 80%, so the prevalence of peptic ulcer, atrophic gastritis and other diseases of the gastrointestinal tract is extremely high in all sections of the population. Topical for our country is the use of standard triple antyhelicobacter therapy, which includes: proton pump inhibitor in combination with clarithromycin + amoxicillin. Such therapy lasting 10 or 14 days allows to completely free the gastrointestinal tract from Helicobacter pylori, and to prevent the further development of pathological process on the mucous membrane. This tactic can successfully prevent the growth of incidence of gastric lymphoma, cancer of the stomach, as well as reduce the likelihood of complications in peptic ulcers.

A New Score for Predicting Acute Gastrointestinal Bleeding in Patients Administered Oral Antiplatelet Drugs.

Antiplatelet drugs may increase the risk of gastrointestinal bleeding. Currently, there is no specific score for predicting the risk of gastrointestinal bleeding caused by oral antiplatelet drugs. In this study, the gastrointestinal bleeding risk score was established and compared with the CRUSADE score in order to reduce the occurrence of clinical gastrointestinal bleeding events. Our study included 4052 patients who received oral antiplatelet drugs. Data were obtained from the patient medical records inpatient system. Cases of acute gastrointestinal bleeding and mortality were recorded. The bleeding score was established by logistic regression, area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. Finally, 171 patients had acute gastrointestinal bleeding. The mortality rates of patients in the bleeding and nonbleeding groups were 24.6 and 4.7%, respectively. A multivariate analysis revealed that an age of >65 years, anemia, recent major bleeding, a history of gastrointestinal bleeding, combined oral anticoagulants, and dual antiplatelet therapy are risk factors, and combined proton pump inhibitors are protective factors for acute gastrointestinal bleeding. We used these risk factors to establish a score for predicting acute gastrointestinal bleeding, named (ABC)2D score. The area under the curve for (ABC)2D score was 0.857 (p < 0.001), higher than the CRUSADE score of 0.693 (p < 0.001). The Hosmer–Lemeshow p value was 0.324. We developed the (ABC)2D score based on seven risk factors (i.e., age, anemia, recent major bleeding, a history of gastrointestinal bleeding, no-proton pump inhibitors use, combined oral anticoagulants, and dual antiplatelet therapy). (ABC)2D score was superior to the CRUSADE score. This new risk-scoring model may help to identify patients at a significant risk of gastrointestinal bleeding.

Spectrum and Clinical Outcome of Motility Disorders on High-Resolution Esophageal Manometry: A Study From a Tertiary Center on Patients With Dysphagia in Pakistan.

ObjectiveThis study aimed to evaluate the outcome of high-resolution esophageal manometry (HRM) in the diagnosis of esophageal motility disorders in a Pakistani population. It also evaluates the outcomes of management of patients with esophageal dysphagia and no structural abnormality on endoscopy.MethodsThis is a cross-sectional study. Patients with symptoms of dysphagia with normal endoscopy were subjected to esophageal manometry and to barium swallow as a part of routine workup. Esophageal motility disorders diagnosed by HRM were compared to barium swallow findings. A follow-up of these patients was done after a one-year interval to evaluate improvement in their symptoms.ResultsA total of 202 patients underwent HRM. There were abnormal findings in 160 patients (79.2%) with achalasia being the most common diagnosis in 35.6% of the total patients. Out of 72 patients diagnosed to have achalasia on HRM, only 46 (32.6%) had similar findings on barium esophagram and this difference is statistically significant, p < 0.001). Among achalasia patients, laparoscopic surgery was performed in 22 (30.5%) patients with 59% patients reporting a good to excellent improvement (>50%) in their symptoms, balloon dilatations were done in 47 (65.27%) patients with a good to excellent improvement in symptoms in 55% patients. Only three patients (5.5%) were given botulinum toxin injections, and two of them had an improvement of >50% in their symptoms. Patients with motility disorders other than achalasia were treated with a combination of proton pump inhibitors (PPIs), calcium channel blockers and selective serotonin reuptake inhibitors (SSRIs).ConclusionAchalasia was the most common esophageal motility disorder in our population. HRM can diagnose significantly more patients with achalasia compared to barium swallow. Likewise, HRM was helpful in detecting other esophageal motility disorders and planning their management.

Сapabilitу of 24-hour esophageal pH-impedance monitoring in the diagnosis of GERD-associated laryngeal diseases

Extraesophageal manifestations of gastroesophageal reflux disease (GERD), despite the improvement of methods of diagnosis and treatment of patients with this pathology, still remain an urgent problem of medicine and cause increased attention of clinicians and researchers. In some cases, patients with GERD do not present typical complaints of heartburn, regurgitation; the disease may manifest extraesophageal manifestations, such as chronic cough, hoarseness, reflux laryngitis, and others caused by the presence of laryngopharyngeal reflux (LFR) – inflammation of the mucous membrane of the upper digestive and respiratory tracts with possible morphological changes associated with direct and indirect (reflex) exposure to gastroduodenal reflux. The occurrence of LFR is possible due to a violation of the motor function of the esophagus and insufficiency of the upper esophageal sphincter, as well as a decrease in the tone of the pharyngeal muscles. The most accessible methods of diagnosis of LFR are registration of complaints according to the questionnaire “index of reflux symptoms”, assessment of the clinical and functional state of the larynx using a visually analog “scale of reflux signs”. A positive response to the empirical use of proton pump inhibitors in combination with procinetics and determination of pepsin content in saliva can also be alternative diagnostic methods. To date, 24-hour pH-impedance monitoring is a method that allows the most accurate diagnosis of all types of reflux, regardless of the pH value, to verify high reflux in combination with its physical properties, as well as to estimate the time of chemical and volumetric esophageal clearance. In addition to performing esophagogastroduodenoscopy, the use of this method is indicated in patients with suspected extraesophageal manifestations of GERD. The article presents clinical examples of patients with extraesophageal manifestations of GERD, describes the possibilities of 24-hour pH-impedance monitoring of the esophagus in the diagnosis of LFR and reflux-associated diseases of the larynx.

S1215 Impact of Medication Compliance on Tissue Response to Proton Pump Inhibitor and Topical Steroid Combination Therapy in Children With Eosinophilic Esophagitis

INTRODUCTION: A combination of proton pump inhibitor and topical steroid (PPI/TS) is used to treat eosinophilic esophagitis (EoE). Improper administration of these drugs can result in persistence of eosinophilic inflammation and lead to refractory EoE, esophageal remodeling, and food impaction. As such, strict adherence to these drugs is emphasized in order to achieve histologic remission. However, the relationship between compliance to PPI/TS and tissue response in children with EoE has not been studied. The aims of this study were to determine the association between PPI/TS compliance and both peak eosinophil count/high power field (PEC) and EoE activity, and to identify patient factors associated with 100% compliance to PPI/TS. METHODS: We prospectively collected self-reported compliance (rated between 0% and 100%) to PPI/TS from 37 children (or caregivers) with EoE on the day of their esophagogastroduodenoscopy (EGD). Their demographics (age, gender, ethnicity), clinical information (duration of EoE, presence of symptoms during the week leading up to their EGD), PEC, and EoE activity status (active or inactive based on PEC threshold of 15) were also gathered. The median [interquartile range (IQR)] for continuous variables and percentages for categorical variables were analyzed. RESULTS: The median age of our cohort was 9 (7–12) years, and most were Caucasian (81%). The median self-reported compliance was 100% (90–100%) [range: 50–100%]. PEC negatively correlated with increasing compliance to PPI/TS (Spearman's rho = −0.33; P = 0.04). The median PEC was significantly lower in children with 100% compliance when compared to those with <100% compliance [3 (0–35) vs. 40 (4–73); P = 0.04]. Furthermore, a significantly smaller proportion of children in the 100% compliance group had active EoE when compared to <100% compliance group [10 (38%) vs. 7 (64%); P = 0.01] (Table 1). Patient demographic and clinical factors were not associated with 100% compliance to PPI/TS. CONCLUSION: This is the first study to evaluate the impact of self-reported compliance to PPI/TS in children with EoE. Our results support strict adherence to PPI/TS irrespective of patient’s demographic or clinical factors in order to achieve favorable tissue response. Adequately powered longitudinal studies utilizing objective methods to ascertain compliance to pharmacologic therapy are warranted to better understand the relationship between compliance to pharmacologic therapy and tissue response in EoE.Table 1.: Characteristics of the cohort

Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing.

Background: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug–drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. Methods: Drug use among nursing home residents during 2017–2018 in the Capital Region of Copenhagen, for drugs with PGx-based dosing guidelines available through the PharmGKB website, were measured. Drug–drug interactions were scored in severity by using drug interaction checkers. Results: The number of residents using drugs with PGx-based actionable dosing guidelines (AG) were 119 out of 141 residents (84.3%). Of these 119 residents, 87 residents used drugs with AG for CYP2C19, 47 residents for CYP2D6, and 42 residents for SLCO1B1. In addition, 30 residents used two drugs with an AG for CYP2C19, and for CYP2D6, it was only seven residents. The most used drugs with AG were clopidogrel (42), pantoprazole (32), simvastatin (30), metoprolol (25), and citalopram (24). The most frequent drug interactions found with warnings were combinations of proton pump inhibitors and clopidogrel underscoring the potential for phenoconversion. Conclusion: this study clearly showed that the majority of the nursing home residents were exposed to drugs or drug combinations for which there exist PGx-based AG. This indeed supports the notion of accessing and accounting for not only drug–gene but also drug–drug–gene interactions as a supplement to medication review.

Effects of STAT3 polymorphisms and pharmacokinetics on the clinical outcomes of gefitinib treatment in patients with EGFR-mutation positive non-small cell lung cancer.

We investigated the correlations among signal transducer and activator of transcription 3 (STAT3) rs4796793C >G polymorphism, gefitinib pharmacokinetics and clinical responses in Japanese patients with non-small cell lung cancer receiving gefitinib therapy. Forty-five patients were enrolled in this study. Plasma trough concentrations (C0 ) of gefitinib at the steady-state were measured by high-performance liquid chromatography. Patients having a gefitinib C0 of at least ≥200ng/mL had significantly longer PFS than patients having a C0 of <200ng/mL (median [95% confidence interval (CI)] PFS: 11.0 [8.2-13.7] and 5.3 [0.0-12.0] months, respectively, P=.042). There were no significant differences in PFS between patients with STAT3 rs4796793C/C and G alleles; however, patients with STAT3 rs4796793C/C having a gefitinib C0 of ≥200ng/mL had significantly longer progression-free survival (PFS) and overall survival (OS) than those with a C0 of <200ng/mL (median [95% CI] PFS: 11.4 [4.1-18.6] and 3.0 [0.0-7.0] months, respectively, P=.008; median [95% CI] OS: 20.6 [7.4-33.7] and 12.6 [10.1-15.1] months, respectively, P=.042). In patients with the STAT3 rs4796793G allele, there were no significant differences in PFS and OS between the two gefitinib C0 groups. In addition, there were no significant differences in PFS or OS according to smoking, presence of proton pump inhibitor combination, or onset of side effects. Clinical outcomes of gefitinib in patients with the STAT3 rs4796793C/C genotype depended on plasma concentrations of gefitinib. In addition to information regarding EGFR mutations, the STAT3 rs4796793C >G polymorphism and gefitinib C0 may be potential predictors of clinical outcomes after beginning of gefitinib therapy.