Acid Suppression Therapy Research Articles

Development and Use of a Calculator to Measure Pediatric Low-Value Care Delivered in US Children’s Hospitals

The scope of low-value care in children's hospitals is poorly understood. To develop and apply a calculator of hospital-based pediatric low-value care to estimate prevalence and cost of low-value services. This cross-sectional study developed and applied a calculator of hospital-based pediatric low-value care to estimate the prevalence and cost of low-value services among 1 011 950 encounters reported in 49 US children's hospitals contributing to the Pediatric Health Information System (PHIS) database. To develop the calculator, a multidisciplinary stakeholder group searched existing pediatric low-value care measures and used an iterative process to identify and operationalize relevant hospital-based measures in the PHIS database. Children with an eligible encounter in 2019 were included in the calculator-applied analysis. Two cohorts were analyzed: an emergency department cohort (with encounters resulting in emergency department discharge) and a hospitalized cohort. Eligible condition-specific hospital encounters. The proportion and volume of encounters in which low-value services were delivered and their associated standardized costs. Measures were ranked by those outcomes. There were 1 011 950 encounters eligible for 1 or more of 30 calculator-included measures in 2019; encounters were incurred by 816 098 unique patients with a median age of 3 years (IQR, 1-8 years). In the emergency department cohort, low-value services delivered in the greatest percentage of encounters were Group A streptococcal testing among children younger than 3 years with pharyngitis (3679 of 9785 [37.6%]), computed tomography scan for minor head injury (7541 of 42 602 [17.7%]), and bronchodilators for treatment of bronchiolitis (8899 of 55 616 [16.0%]). In the hospitalized cohort, low-value care was most prevalent for broad-spectrum antibiotics in the treatment of community-acquired pneumonia (3406 of 5658 [60.2%]), acid suppression therapy for infants with esophageal reflux (3814 of 7507 of [50.8%]), and blood cultures for uncomplicated community-acquired pneumonia (2277 of 5823 [39.1%]). Measured low-value services generated nearly $17 million in total standardized cost. The costliest services in the emergency department cohort were computed tomography scan for abdominal pain (approximately $1.8 million) and minor head injury (approximately $1.5 million) and chest radiography for asthma (approximately $1.1 million). The costliest services in the hospitalized cohort were receipt of 2 or more concurrent antipsychotics (approximately $2.4 million), and chest radiography for bronchiolitis ($801 680) and asthma ($625 866). This cross-sectional analysis found that low-value care for some pediatric services was prevalent and costly. Measuring receipt of low-value services across conditions informs prioritization of deimplementation efforts. Continued use of this calculator may establish trends in low-value care delivery.

Complex assessment of esophageal acidification and motor function in patients with Barrett's esophagus on antisecretory therapy

To determine predictors of insufficient effectiveness of proton pump inhibitors based on the parameters of 24-hours pH-impedance and features of motor function of the esophagus in patients with Barrett's esophagus. 17 patients with histologically verified Barrett's esophagus undergoing acid-suppressive therapy were examined. All patients underwent 24-hours pH-impedance and high-resolution esophageal manometry. According to daily pH-impedance, group 1 consisted of 11 patients with an adequate response to antisecretory therapy, group 2 6 patients with insufficient effectiveness of antisecretory therapy, 5 of whom had no clinical manifestations. The total number of reflux averaged 52 and 91, respectively, in groups 1 and 2. The average number of acid reflux in group 1 was 4.36, in group 2 40.5. The average number of non-acid reflux prevailed in patients of group 2, averaging 58, compared with group 1, where the average was 47. According to the results of high-resolution esophageal manometry, when assessing the structure and function of the esophageal-gastric junction, violations were detected in 6 out of 17 patients. Disorders of the motor function of the thoracic esophagus were detected in 10 out of 17 patients. The tone of the lower esophageal sphincter in group 1 patients was significantly higher in comparison with patients in group 2. A number of patients with Barrett's esophagus have insufficient effectiveness of antisecretory therapy, which may not manifest itself clinically and thereby increase the risk of progression. There was a tendency to more frequent motor disorders in the group with insufficient effectiveness of antisecretory therapy, as well as significantly lower tone of the lower esophageal sphincter, which may be a potential predictor of suboptimal effectiveness of antisecretory therapy.

Communicating Guideline Recommendations Using Graphic Narrative Versus Text-Based Broadcast Screensavers: Design and Implementation Study.

BackgroundThe use of graphic narratives, defined as stories that use images for narration, is growing in health communication.ObjectiveThe aim of this study was to describe the design and implementation of a graphic narrative screensaver (GNS) to communicate a guideline recommendation (ie, avoiding low-value acid suppressive therapy [AST] use in hospital inpatients) and examine the comparative effectiveness of the GNS versus a text-based screensaver (TBS) on clinical practice (ie, low-value AST prescriptions) and clinician recall.MethodsDuring a 2-year period, the GNS and the TBS were displayed on inpatient clinical workstations. The numbers of new AST prescriptions were examined in the four quarters before, the three quarters during, and the one quarter after screensavers were implemented. Additionally, an electronic survey was sent to resident physicians 1 year after the intervention to assess screensaver recall.ResultsDesigning an aesthetically engaging graphic that could be rapidly understood was critical in the development of the GNS. The odds of receiving an AST prescription on medicine and medicine subspecialty services after the screensavers were implemented were lower for all four quarters (ie, GNS and TBS broadcast together, only TBS broadcast, only GNS broadcast, and no AST screensavers broadcast) compared to the quarter prior to implementation (odds ratio [OR] 0.85, 95% CI 0.78-0.92; OR 0.89, 95% CI 0.82-0.97; OR 0.87, 95% CI 0.80-0.95; and OR 0.81, 95% CI 0.75-0.89, respectively; P<.001 for all comparisons). There were no statistically significant decreases for other high-volume services, such as the surgical services. These declines appear to have begun prior to screensaver implementation. When surveyed about the screensaver content 1 year later, resident physicians recalled both the GNS and TBS (43/70, 61%, vs 54/70, 77%; P=.07) and those who recalled the screensaver were more likely to recall the main message of the GNS compared to the TBS (30/43, 70%, vs 1/54, 2%; P<.001).ConclusionsIt is feasible to use a graphic narrative embedded in a broadcast screensaver to communicate a guideline recommendation, but further study is needed to determine the impact of graphic narratives on clinical practice.

98. Outcomes of Clinical Decision Support for Outpatient Management of Clostridioides difficile Infection

BackgroundOur antimicrobial stewardship program identified high rates of suboptimal metronidazole prescribing for Clostridioides difficile infection (CDI) within ambulatory clinics. An outpatient best practice advisory (BPA) was implemented to notify prescribers “Vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI. MethodsWe conducted an IRB approved quasi-experiment before and after implementation of the BPA on June 3, 2020. Inclusion: Adult patients diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between 11/1/2019 and 11/30/2020. Exclusion: fulminant CDI. Primary endpoint: guideline-concordant CDI therapy, defined as oral vancomycin or fidaxomicin. Oral metronidazole was considered guideline-concordant if prescribed due to cost barrier. Secondary endpoints: reasons for alternative CDI therapy, patient outcomes, prescriber response to the BPA. Descriptive and bivariate analyses were completed.Results189 patients were included in the study, 92 before and 97 after the BPA. Median age: 59 years, 31% male, 75% Caucasian, 30% with CDI-related comorbidities, 35% with healthcare exposure, 65% with antibiotic exposure, 44% with gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 out of 26 times and optimized the therapy of 16 patients in six months. Guideline-concordant therapy increased after implementation of the BPA (72% vs. 91%, p=0.001) (Figure 1). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA (Figure 2). Reasons for alternative CDI therapy included medication cost, lack of insurance coverage, and non-CDI infection. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs. 7%, p< 0.001). Figure 1. Guideline-concordant CDI therapy Figure 2. Specific CDI therapy ConclusionClinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.Disclosures Susan L. Davis, PharmD, Nothing to disclose Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

Heartburn as a Marker of the Success of Acid Suppression Therapy in Chronic Cough

PurposeGastro-oesophageal reflux disease (GORD) is commonly thought to play an important role in chronic cough and patients are often empirically treated with acid suppression therapy. We sought to investigate the response rate to acid suppression treatment in patients with and without heartburn attending two specialist cough clinics.MethodsA retrospective review of 558 consecutive patients referred to two specialist cough clinics was performed (UK and USA). Patients who were treated with acid suppression were included and their documented response to treatment was collected. Binary logistic regression was used to ascertain the value of reported heartburn in predicting the response of chronic cough to acid suppression therapy.ResultsOf 558 consecutive referrals, 238 patients were excluded due to missing data or cough duration of < 8 weeks. The remaining 320 patients were predominantly female (76%), with mean age 61 yrs (± 13) and 96.8% non-smokers, with chronic cough for 36 (18–117) months. Of 72 patients with heartburn, 20 (28%) noted improvement in their cough with acid suppression, whereas of 248 without heartburn, only 35 (14%) responded. Patients reporting heartburn were 2.7 (95% C.I. 1.3–5.6) times more likely to respond to acid suppression therapy (p = 0.007).ConclusionIn specialist cough clinics, few patients report a response of their chronic cough to acid suppression therapy. Nonetheless, heartburn is a useful predictor substantially increasing the likelihood of benefit.

Risk of Enteric Infection in Patients with Gastric Acid Supressive Drugs: A Population-Based Case-Control Study.

: BackgroundLong-term use of gastric-acid-suppressive drugs is known to be associated with several adverse effects. However, the association between enteric infection and acid suppression therapy is still uncertain. This study aimed to evaluate the association between gastric acid suppression and the risk of enteric infection. Materials and Methods: We conducted a population-based case-control study using the data from Chang Gung Research Database (CGRD) in Taiwan. Between January 2008 and December 2017, a total of 154,590 adult inpatients (age > 18) were identified. A pool of potential eligible controls according to four propensity scores matching by sex, age, and index year were extracted (n = 89,925). Subjects with missing data or who received less than 7 days of proton pump inhibitors (PPIs) and/or H2-receptor antagonists (H2RAs) were excluded. Finally, 17,186 cases and 69,708 corresponding controls were selected for analysis. The use of PPIs and H2RAs, the result of microbiological samples, and co-morbidity conditions have been analyzed. Confounders were controlled by conditional logistic regression. Results: 32.84% of patients in the case group used PPIs, compared with 7.48% in the control group. Of patients in the case group, 9.9% used H2RAs, compared with 6.9% in the control group. Of patients in the case group, 8.3% used a combination of PPIs and H2RAs, compared with 2.7% in the control group. The most common etiological pathogens were Enterococcus (44.8%), Clostridioides difficile (34.5%), and Salmonella spp. (10.2%). The adjusted odds ratio (OR) for PPI use with enteric infection was 5.526 (95% confidence interval [CI], 5.274–5.791). For H2RAs, the adjusted odds ratio was 1.339 (95% confidence interval [CI], 1.261–1.424). Compared to the control group, persons with enteric infection had more frequent acid-suppressive agent usage. Conclusions: This study demonstrates that gastric-acid-suppressive drug use is associated with an increased risk of enteric infection after adjusting for potential biases and confounders.

Acid Suppression Therapy for the Empirical Treatment of Nausea and Vomiting in Hospitalized Pediatric Patients

Objective: To investigate and compare the safety and efficacy of the empirical use of Histamine-2-receptor antagonists (H2RAs) and Proton pump inhibitors (PPIs), for the treatment of unspecified nausea and vomiting (NV) in hospitalized children.&#x0D; Methods: The retrospective cohort study was conducted at King Abdulaziz Medical City in Riyadh (KAMC-R) and included pediatric patients ≤14 years who received acid suppression therapy (AST), H2RAs or PPIs, for the treatment of unspecified NV between April 30, 2018, and April 30, 2019. The primary outcome was the complete resolution of NV within three days of AST. The secondary outcomes were the frequency of rescue medication use, the number of vomiting episodes since starting the AST, and the adverse drug reactions (ADRs).&#x0D; Results: Sixty-two patients were included in the study, 25 (40.3%) were in the H2RAs group and 37 (59.7%) in the PPIs group. The mean age was 3.69 ± 4.13 years, with the majority male (64.5%). Overall, 87% (n=54) of the sample had complete resolution of NV within 3 days of the AST therapy with no difference between the H2RAs and PPIs groups (p=0.344). The number of NV episodes from initiating the AST until the complete resolution was similar between the groups. In total, 14 patients (25.9%) required rescue therapy with granisetron, 6 (26.1%) in the H2RAs group compared to 8 (25.8%) in the PPIs group. There was no difference in the number of the required granisetron doses or the incidence of ADRs.&#x0D; Conclusion: Both PPIs and H2RAs were effective and safe for the treatment of unspecified NV in hospitalized pediatric patients. The selection of either agent should be based on other factors.&#x0D; Keywords: Pediatric; Nausea and vomiting; Proton pump inhibitor; Histamine-2-receptor antagonist; Granisetron.

S3570 One and Done? Revisiting Need for Repeat Esophageal Manometry in Patients With Persistent Symptoms

Introduction: Achalasia is a motility disorder characterized by the absence of esophageal peristalsis and failure of the LES to relax in response to swallowing. High resolution manometry (HRM) has been established as the gold standard for diagnosis; however, the utility of repeat manometry has been investigated in only a limited number of reports. Whether repeat manometry provides new information or changes the diagnosis remains unclear Case Description/Methods: 70y/o female with GERD, PUD, cervical spondylosis, and rheumatoid arthritis, presented in 2015 with dysphagia to solids. Initial work-up included EGD which showed an esophageal web. She was started on acid suppression therapy without improvement. In 2017 she underwent HRM which showed an abnormal median integrated relaxation pressure of 39.6(n< 15mmHg) and an elevated upper esophageal sphincter relaxation pressure of 13.7(n< 12mmHg). 70% of swallows were failed with 30% of swallows peristaltic with normal distal contractile integral. There was incomplete bolus clearance in all swallows. Patient met Chicago Classification 3.0 criteria for esophagogastric junction outflow obstruction. However, given the large presence of non-peristaltic swallows, the possibility of an evolving achalasia was considered. Due to worsening symptoms, patient underwent barium esophagram (BE) ;in 2018 which did not suggest achalasia. There was however, small residual of contrast in the distal esophagus with delayed emptying suggesting a motility disorder. She then underwent video swallow study which was unrevealing. She again underwent BE; in 2019 revealing a prominent cricopharyngeus muscle causing narrowing of the esophageal lumen during the swallowing phase. She subsequently underwent repeat HRM which was consistent with Type II Achalasia per Chicago classification 3.0. LES pressure was elevated at 43.8 mmHg, UES pressure was normal (6.2 mmHg). 100% of all contractions had pan esophageal pressurization deeming them non-peristaltic. Patient had incomplete bolus clearance in all swallows. Of note, patient was not on any medications, including benzodiazepines or opioids, that would impact motility studies. Due to persistent symptoms, patient underwent peroral endoscopic myotomy with significant improvement of symptoms. Discussion: HRM is the gold standard for identifying causes of esophageal dysmotility. In patients whose symptoms progress over time, there is high utility in performing repeat manometry to evaluate the cause of their dynamic symptoms, as treatment options may change

S351 A Gastroenterology-Based Multi-Disciplinary Weight Management Program Reduces Acid Suppression Therapy in Patients With GERD: A Prospective Cohort Study

S351 A Gastroenterology-Based Multi-Disciplinary Weight Management Program Reduces Acid Suppression Therapy in Patients With GERD: A Prospective Cohort Study

S1427 Is Acid Suppression Therapy Associated With Increased Risk of Cardia Gastric Cancer? A Meta-Analysis

S1427 Is Acid Suppression Therapy Associated With Increased Risk of Cardia Gastric Cancer? A Meta-Analysis

A contemporary review of rearranged during transfection-selective inhibitors.

Rearranged during transfection genes are present in 1-2% of patients who have non-small cell lung cancer and 10-30% of patients with papillary thyroid cancer. The objective of this article is to review the current rearranged during transfection inhibitors indicated for patients with rearranged during transfection-mutated cancers and their future directions.Data sources: The pivotal phase I/II studies for selpercatinib and pralsetinib were evaluated. Current studies on rearranged during transfection inhibitors were searched on ClinicalTrials.gov using the key word "RET."Data summary: Selpercatinib and pralsetinib were the first two U.S. Food and Drug Administration-approved rearranged during transfection-selective inhibitors for advanced or metastatic rearranged during transfection fusion-positive non-small cell lung cancer, rearranged during transfection-mutant medullary thyroid cancer, and rearranged during transfection fusion-positive thyroid cancer. Both agents showed promising efficacy with objective response rate ranging from 60% to 73% in all aforementioned rearranged during transfection-mutated cancers. Additionally, benefits were seen even in patients with intracranial metastasis at baseline. Both showed favorable safety profiles. Some common class adverse events included elevated liver function tests and hypertension. Hematologic side effects such as anemia and neutropenia were more common with pralsetinib. Selpercatinib had interactions with acid suppressive therapy and specific instructions when used concomitantly. While the rearranged during transfection inhibitors are generally well-tolerated, each agent possesses slightly different efficacy, side-effect profile, and drug-drug interactions.

Outcomes of clinical decision support for outpatient management of Clostridioides difficile infection.

To determine the impact of clinical decision support on guideline-concordant Clostridioides difficile infection (CDI) treatment. Quasi-experimental study in >50 ambulatory clinics. Primary, specialty, and urgent-care clinics. Adult patients were eligible for inclusion if they were diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between November 1, 2019, and November 30, 2020. An outpatient best practice advisory (BPA) was implemented to notify prescribers that "vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection" when metronidazole was prescribed to a patient with CDI. In total, 189 patients were included in the study: 92 before the BPA and 97 after the BPA. Their median age was 59 years; 31% were male; 75% were white; 30% had CDI-related comorbidities; 35% had healthcare exposure; 65% had antibiotic exposure; 44% had gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 of 26 times and was used to optimize the therapy of 16 patients in 6 months. Guideline-concordant therapy increased after implementation of the BPA (72% vs 91%; P = .001). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs 7%; P < .001). Clinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.

Gastric acid suppression, lifestyle factors and intestinal carriage of ESBL and carbapenemase-producing Enterobacterales: a nationwide population-based study.

BackgroundGastric acid-suppressive therapy has been suggested to increase the risk for intestinal carriage of MDR Enterobacterales, but there is scarce community-based evidence substantiating this risk.ObjectivesTo investigate if acid-suppressant use is associated with a risk of intestinal carriage of ESBL and carbapenemase-producing Enterobacterales (ESBL-E) in the open population, and to assess possible modifying factors.MethodsWithin the framework of a nationwide seroprevalence study, we identified a population-based cross-sectional cohort comprising 2746 adults (≥18 years), who provided stool specimens between February 2016 and June 2017. Specimens were tested by phenotypic assays and confirmatory genotype analysis to detect carriage of ESBL-E. Covariate data were extracted from self-administered questionnaires. ORs and 95% CIs were estimated using multivariable multilevel logistic regression, controlling for confounders informed by directed acyclic graphs.ResultsAmong 2746 participants, 316 (11.5%) used acid suppressants; the prevalence of ESBL-E carriage was 7.4% (95% CI, 6.1%–8.6%). Current use of acid suppressants was not associated with ESBL-E carriage (adjusted OR [aOR], 1.05; 95% CI, 0.64–1.74); lifestyle and comorbidity did not modify this association. A higher BMI (≥25 kg/m2) (aOR, 1.42 [95% CI, 1.02–1.98]), non-Western ethnic origin (aOR, 1.96 [95% CI, 1.34–2.87]), travel to Eastern-Mediterranean, Western-Pacific or South-East Asia regions (aOR, 3.16 [95% CI, 1.71–5.83]) were associated with ESBL-E carriage. Sensitivity analyses confirmed these results; spline analysis supported a BMI-associated risk.ConclusionsIn this open population study, current use of acid suppressants was not associated with ESBL-E carriage. Travel to high-endemic regions and non-Western ethnicity were confirmed as risk factors, while a higher BMI emerged as a potential new risk for ESBL-E carriage.

Barrett's Epithelium to Esophageal Adenocarcinoma: Is There a "Point of No Return"?

Background: Esophageal adenocarcinoma (EA) arises from Barrett’s epithelium (BE), and chronic gastroesophageal reflux disease is considered the strongest risk factor for disease progression. All BE patients undergo acid suppressive therapy, surveillance, and BE removal by surgery or endoscopic ablation, yet the incidence of EAC continues to increase. Despite the known side effects and mortality, the one-size-fits-all approach is the standard clinical management as there are no reliable methods for risk stratification.Methods: Paired-end Illumina NextSeq500 RNA sequencing was performed on total RNA extracted from 20-week intervals (0, 20, 40, and 60 W) of an in vitro BE carcinogenesis (BEC) model to construct time series global gene expression patterns (GEPs). The cells from two strategic time points (20 and 40 W) based on the GEPs were grown for another 20 weeks, with and without further acid and bile salt (ABS) stimulation, and the recurrent neoplastic cell phenotypes were evaluated.Results: Hierarchical clustering of 866 genes with ≥ twofold change in transcript levels across the four time points revealed maximum variation between the BEC20W and BEC40W cells. Enrichment analysis confirmed that the genes altered ≥ twofold during this window period associated with carcinogenesis and malignancy. Intriguingly, the BEC20W cells required further ABS exposure to gain neoplastic changes, but the BEC40W cells progressed to malignant transformation after 20 weeks even in the absence of additional ABS.Discussion: The transcriptomic gene expression patterns in the BEC model demonstrate evidence of a clear threshold in the progression of BE to malignancy. Catastrophic transcriptomic changes during a window period culminate in the commitment of the BE cells to a “point of no return,” and removal of ABS is not effective in preventing their malignant transformation. Discerning this “point of no return” during BE surveillance by tracking the GEPs has the potential to evaluate risk of BE progression and enable personalized clinical management.

Current practice of stress ulcer prophylaxis in a surgical patient cohort in a German university hospital

IntroductionStress ulcer prophylaxis (SUP) has been a widespread practice both in intensive care units (ICU) and internal wards at the beginning of the twenty-first century. Clinical data suggests an important overuse of acid suppressive therapy (AST) for this indication. Data on current clinical practice of SUP in surgical patients in a non-ICU setting are spares. In the light of a growing number of reports on serious side effects of AST, this study evaluates the use of AST for SUP in a normal surgical ward in a German university hospital.MethodsBetween January 2016 and June 2016, SUP was analysed retrospectively in 1132 consecutive patients of the Department of Surgery of the Universitätsmedizin Greifswald.ResultsThe patients managed with and without SUP were similar with respect to demographic data and treatment with anticoagulants, SSRI and glucocorticoids. Patients with SUP were treated more frequently by cyclooxygenase inhibiting drugs (NSAID, COX2-inhibitors), were more frequently treated in the intermediated care unit and had a longer hospital stay. Risk factors for the development of stress ulcers were similarly present in patient groups managed with and without SUP. About 85.7–99.6% of patients were given SUP without an adequate risk for stress ulcer development, depending on the method used for risk assessment.DiscussionStill today, SUP is widely overused in non-ICU surgical patients. Information campaigns on risk factors for stress ulcer development and standard operating procedures for SUP are required to limit potential side effects and increased treatment costs.

Strategies that Reduce Post-endoscopic Submucosal Dissection Bleeding

Bleeding after endoscopic submucosal dissection (ESD), one of the most common postprocedural adverse events, is the main cause of increased readmission rates and hospital costs. Generally, the incidence of post-ESD bleeding is estimated to be about 5%. However, the incidence of bleeding is particularly increased in high-risk patients. In particular, it has an incidence of over 50% in patients that use antithrombotic agents. The well-known risk factors for post-ESD bleeding include antithrombotic therapy, lesions in the proximal stomach, specimen size &gt;4 cm, and concomitant renal disease. Currently, the number of patients at a high risk of post-ESD bleeding has been increasing. This may be due to the aging society and the increase in the usage of antithrombotic agents. Therefore, several strategies have been employed to prevent post-ESD bleeding. These strategies include acid inhibition therapy, preventive hemostasis using Doppler endoscopic ultrasound and artery-selective clipping, second look endoscopy, the closings method, and the shield methods. However, these methods are technically demanding, which hinders their wide usage in clinical practice. Recently, several hemostatic powders have been developed and clinically used in the treatment of gastrointestinal bleeding. In this article, we review the risk factors for post-ESD bleeding and the recently introduced prevention methods. Moreover, we aimed to explore realistic and appropriate strategies for the prevention of post-ESD bleeding.

Нестероидные противовоспалительные средства: современное представление о механизмах повреждения пищеварительного тракта, минусы препаратов патогенетического лечения и перспективы биологической терапии НПВС-индуцированной эзофагогастроэнтероколонопатии

Актуальность. Нестероидные противовоспалительные средства (НПВС) ежедневно применяют более чем 30 млн человек, а их арсенал насчитывает свыше 80 препаратов и около 1000 созданных на их основе лекарственных форм. Они широко используются во многих сферах медицины и являются одной из наиболее клинически значимых групп лекарственных средств. Однако при использовании НПВС достаточно часто могут возникать побочные реакции, наиболее распространенными из них являются повреждения желудочно-кишечного тракта. Цель: охарактеризовать со­временное представление о механизмах повреждения пищеварительного тракта НПВС, оценить недостатки существующих препаратов патогенетического лечения и перспективы биологической терапии НПВС-индуцированной эзофагогастроэнтероколонопатии криоконсервированным экстрактом плаценты человека. Материалы и методы. Проведен анализ работ, опубликованных в 2010–2020 гг., в которых освещались сведения об эпидемиологии, патогенезе, диагностике и тактике лечения поражений пищевода и желудочно-кишечного тракта, индуцированных НПВС, а также биологические свойства криоконсервированного экстракта плаценты человека как средства биологической терапии. Результаты. Лечение НПВС-индуцированной эзофагогастроэнтероколонопатии классически направлено на кислотосупрессивную терапию (ингибиторы протонной помпы, Н2-гистаминоблокаторы и др.), применение гастроцитопротекторов (де-нол, сукральфат и др.) и препаратов, восстанавливающих содержание простагландинов в слизистой оболочке (мизопростол, ребамипид и др.). Однако все указанные группы лекарственных средств недостаточно удовлетворяют клиницистов, поскольку направлены преимущественно на лечение НПВС-гастропатии и имеют побочные эффекты. Новым перспективным направлением повышения безопасности НПВС на сегодняшний день является применение средств биологической терапии, источниками которых выступают микроорганизмы, органы и ткани растительного или животного происхождения, клетки или жидкости (в том числе кровь и плазма) человеческого или животного происхождения и биотехнологические клеточные конструкции. Выводы. Использование НПВС значительно ограничивается присущими им побочными эффектами, наи­более распространенными являются нарушения со стороны желудочно-кишечного тракта. Криоконсервированный экстракт плаценты человека является перспективным средством биологической терапии ульцерогенных повреждений желудочно-кишечного тракта, индуцированных НПВС.

Patients, Prescribers, and Institutional Factors Associated with Inappropriate Use of Acid Suppressive Therapy in Medical Wards: An Experience of a Single-Center in Saudi Arabia.

PurposeTo identify factors associated with inappropriate acid-suppressive therapy (AST) use in hospitalized medical ward patients.Patients and MethodsThis was a combined retrospective cohort study reviewing the electronic medical records of medical ward in a secondary university hospital between January 2018 and July 2019, in addition to prescriber surveys about AST knowledge. We included adult patients (≥18 years old) admitted to the medical ward who received at least one dose of AST during their hospitalization. Statistical analyses included descriptive statistics and logistic regression.ResultsA total of 335 patients were included. Most of the patients were female (66.6%), with a mean age of 42.37 ± 17.72 years; 76% (n=256) of the study subjects were prescribed AST for an inappropriate indication. Patients who were not receiving any home medications associated with high bleeding risk had higher odds of being prescribed AST inappropriately (OR, 4.06; 95% CI, 1.09–13.8). A total of 27 physicians completed the prescriber survey, and the average prescriber’s knowledge score was 46.8 ± 15.6%. This score did not differ by the prescriber’s position.ConclusionThis study demonstrated the overuse of AST in the medical ward. Therefore, improving providers’ awareness about AST and implementing an AST stewardship program in institutions is necessary to limit this long-lasting issue.

Interactions between epidermal growth factor receptor tyrosine kinase inhibitors and proton-pump inhibitors/histamine type-2 receptor antagonists in non-small cell lung cancer: a systematic review and meta-analysis.

BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are increasingly used for advanced non-small cell lung cancer (NSCLC) as first-line therapy. The bioavailability and efficacy of oral EGFR-TKIs could be affected by acid suppression (AS) therapy such as PPIs and H2RAs which are reported to be over-prescribed. Hence, there is a need to investigate the effect of AS on the overall survival (OS), progression-free survival (PFS) and adverse effect profile in patients treated with EGFR TKIs.MethodsAn electronic database search of Medline and Embase was performed following PRISMA guidelines on 17 January 2021. Studies analyzing interactions between EGFR TKIs and PPIs/H2RAs in NSCLC patients were included. s, non-English or non-Japanese studies or studies using non-EGFR TKIs were excluded. Hazard ratios (HRs) were pooled using generic inverse variance random effects model. Effect sizes for dichotomous variables were pooled using Mantel-Haenszel random effects model. Significance was considered at P≤0.05. Heterogeneity was assessed with Cochran Q-test and I2 test. Publication bias was assessed with funnel plots. The assessment of quality and risk of bias of randomized and non-randomized studies were undertaken with RoB 2 and the ROBINS-I tool respectively.ResultsOut of 1,173 potentially relevant articles, 14 articles were included in the final analysis. The pooled prevalence of AS in patients taking EGFR TKI was 30.71% in 4,010 individuals. Patients who were treated only with EGFR TKI had significantly better OS (HR =1.46, 95% CI: 1.27–1.72; P<0.00001) and PFS (HR =1.63, 95% CI: 1.35–1.98; P<0.00001). The OS for EGFR mutation positive patients only was as similarly significant as the OS in all patients taking EGFR TKI, while the PFS in mutation positive patients was significantly worsened with AS. PPIs resulted in a significantly worsened OS and PFS but H2RAs did not produce significantly different OS and PFS between AS and non-AS users. There were no significant differences in the incidence of rash (OR =0.81, 95% CI: 0.50–1.32; P=0.40), diarrhoea (OR =1.03, 95% CI: 0.63–1.67; P=0.91) or other adverse effects.ConclusionsCo-administration of AS medications with first-generation EGFR-TKIs in NSCLC worsens survival outcomes. Physicians should only prescribe AS medications when absolutely clinically indicated.

Controversial link between proton pump inhibitors and anticancer agents: review of the literature.

Drug-drug interactions represent a topic of great interest, not only due to the risk of unexpected adverse events but also due to the possibility of altering the effectiveness of a specific treatment. Inappropriate or concomitant use of drugs can often lead to changes in the bioavailability of various compounds, resulting in pharmacokinetic alterations. A recent example is the concomitant administration of proton pump inhibitors (PPIs) and anticancer agents. PPIs are overused beyond their classic indications, resulting in a high risk of interactions with other drugs, such as anticancer agents, both PO and intravenous. However, the real clinical impact of concomitant acid suppression therapy and anticancer therapies remains controversial and is not yet fully understood. Certainly, the gut microbiota plays a key role in regulating the response of the immune system, and PPIs can significantly alter the gut microbiome, resulting in gut dysbiosis. Indeed, while the link sometimes appears to lead to negative outcomes, as in the case of immunotherapy, oral capecitabine, or tyrosine kinase inhibitors, in other cases, it seems to enhance the effectiveness of intravenous chemotherapy. In this review, I analyse the possible drug interactions between PPIs and the main classes of anticancer drugs.