Use Of Acid-suppressive Medication Research Articles

Brief Resolved Unexplained Events Symptoms Frequently Result in Inappropriate Gastrointestinal Diagnoses and Treatment

ObjectiveTo determine associations between presenting symptoms and oropharyngeal dysphagia diagnoses, gastroesophageal reflux disease (GERD) diagnoses, and treatment with acid suppression medication in infants with brief resolved unexplained event (BRUE). Study designWe performed a prospective cohort study of infants with BRUE to review presenting symptoms and their potential impact on testing and treatment. Videofluoroscopic swallow study (VFSS) results and explanatory diagnoses were obtained from medical record review; acid suppression use was determined by parental survey. Binary and multivariable logistic regression models were used to evaluate associations between presenting symptoms and obtaining VFSS, VFSS results, GERD diagnoses, and acid suppression medication. ResultsPresenting symptoms were varied in 157 subjects enrolled at 51.0±5.3 days of age, with many symptoms that may be related to GERD or dysphagia. Of these, 28% underwent VFSS with 71% abnormal. Overall, 42% had their BRUE attributed to GERD and 33% were treated with acid suppression during follow-up. Presenting symptoms were significantly associated with the decision to obtain VFSS but not with abnormal VFSS results. Presenting symptoms were also associated with provision of GERD explanatory diagnoses. Both presenting symptoms and GERD explanatory diagnoses were associated with acid suppression use (aOR 2.3, 95% CI 1.03-5.3, p=0.04). ConclusionsPresenting symptoms may play a role in clinicians’ decisions about which BRUE patients undergo VFSS but are unreliable to make a diagnosis of oropharyngeal dysphagia. Presenting symptoms may also influence assignment of a GERD explanatory diagnoses that is associated with increased acid suppression medication use.

Missed Opportunities: the Timing and Frequency of Screening Colonoscopy in Patients That Develop Esophageal Adenocarcinoma

IntroductionScreening colonoscopy (SC) is widely accepted and has been shown to decrease the rate of colorectal cancer death. Guidelines and acceptance of screening for Barrett’s esophagus (BE) are less established despite the fact that esophageal adenocarcinoma (EA) remains the fastest increasing cancer in the USA. The aim of this study was to assess the timing and frequency of SC in patients ultimately found to have EA and to evaluate the presence of symptoms and risk factors that might have prompted an esophagogastroduodenoscopy (EGD) and potentially earlier diagnosis of the EA. MethodsA retrospective chart review was performed to identify all patients who were referred to a single center with esophageal cancer between July 2016 and November 2022. Patients with any histology other than adenocarcinoma were excluded. ResultsThere were 221 patients referred with EA. Of these, a SC had been done prior to the diagnosis of EA in 108 patients (49%): 96 men and 12 women. A total of 203 SC had been done (range 1–7 per patient), and 47% of patients had more than 1 SC. The median interval from the last SC to the diagnosis of EA was 2.9 years. At the time of SC, gastroesophageal reflux disease (GERD) symptoms or chronic acid suppression medication use was reported by 81% of patients, and 80% had an American Society of Gastrointestinal Endoscopy (ASGE) indication for a screening EGD. Only 19 patients (18%) that had a SC had an EGD at any time prior to the diagnosis of EA, and in these patients, 74% had erosive esophagitis or BE. The EA in most patients was stage III or IV and associated with lymph node metastases. ConclusionsNearly one-half of patients ultimately diagnosed with EA had one or more SCs, and most of these patients had GERD symptoms, were using acid suppression medications or had an ASGE indication for a screening EGD. Despite this, only 18% had an EGD prior to the EA diagnosis. The addition of an EGD at the time of SC in these patients may have allowed the detection of BE or EA at an early, endoscopically curable stage and represents a missed opportunity to intervene in the natural history of this disease.

Autoimmune and immune-mediated inflammatory diseases after exposure to acid-suppressive medication: A systematic review and meta-analysis.

Pharmacovigilance risk signals have proposed a relationship between the use of acid-suppressive medications and the development of certain autoimmune and immune-mediated inflammatory diseases. A systematic review and a meta-analysis was performed. We reviewed MEDLINE (Ovid) and Scopus for comparative observational studies between these diseases and previous exposure to proton-pump inhibitors (PPI), H2-receptor antagonists (H2RA), and antacids. The protocol was registered on the PROSPERO database (CRD42020192715). From 3,191 citations, 25 articles were eligible and covered 16 diseases. Microscopic colitis (MC) was studied the most (7 studies). In a random-effects meta-analysis, there was low certainty evidence (GRADE approach) of a non-significant relationship between exposure to any PPIs and MC (meta-OR 3.28, 95% CI 0.98-11.0, I2 98.2%, six studies, 4,436 PPI-exposed MC patients). Moderate certainty evidence pointed towards large odds of collagenous colitis after exposure to lansoprazole (meta-OR 14.5, 95% CI 9.37-22.3, I2 10.2%, three studies, 1,725 lansoprazole-exposed patients). After PPI exposure, the risk of rheumatoid arthritis was slightly increased based on low certainty evidence from two cohort studies totaling 475 diagnoses (meta-RR 1.62, 95% CI 1.12-2.34, I2 34.5%). In patients with MC, it would be reasonable to carefully review the indication of PPI, especially in CC patients using lansoprazole.

Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

Existing observational data have indicated positive associations of acid-suppressive medication (ASM) use in prenatal and early life with allergic diseases in children; however, no study to date has accounted for confounding by indication or within-familial factors. To evaluate the association of prenatal or infant exposure to ASMs with risk of allergic diseases in children. This nationwide, cohort study included data from South Korea's National Health Insurance Service mother-child-linked database from January 1, 2007, to December 31, 2020. Participants included mother-child pairs of neonates born from April 1, 2008, to December 31, 2019. Prenatal and infant exposure to ASMs (histamine 2 receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]). Composite and individual outcomes of allergic diseases (asthma, allergic rhinitis, atopic dermatitis, and food allergy) in children (followed up to 13 years of age) were assessed. The ASM-exposed individuals were compared with unexposed individuals in propensity score (PS)-matched and sibling-matched analyses to control for various potential confounders and within-familial factors. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards regression models. The study included 4 149 257 mother-child pairs. Prenatal exposure analyses included 808 067 PS-matched pairs (763 755 received H2RAs, 36 529 received PPIs) among women with a mean (SD) age of 31.8 (4.2) years. The PS-matched HR was 1.01 (95% CI, 1.01-1.02) for allergic diseases overall (asthma: HR, 1.02 [95% CI, 1.01-1.03]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.02]; atopic dermatitis: HR, 1.02 [95% CI, 1.01-1.02]; food allergy: HR, 1.03 [95% CI, 0.98-1.07]); in sibling-matched analyses, the HRs were similar to those of PS-matched analyses but were not significant (allergic diseases: HR, 1.01; 95% CI, 0.997-1.01). Infant exposure analyses included 84 263 PS-matched pairs (74 188 received H2RAs, 7496 received PPIs). The PS-matched HR was 1.06 (95% CI, 1.05-1.07) for allergic diseases overall (asthma: HR, 1.16 [95% CI, 1.14-1.18]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.03]; atopic dermatitis: HR, 1.05 [95% CI, 1.02-1.08]; food allergy: HR, 1.28 [95% CI, 1.10-1.49]); asthma risk (HR, 1.13; 95% CI, 1.09-1.17) remained significantly higher among children exposed to ASMs during infancy in sibling-matched analyses. The findings were similar for H2RAs and PPIs analyzed separately and were robust across all sensitivity analyses. The findings of this cohort study suggest that there is no association between prenatal exposure to ASMs and allergic diseases in offspring. However, infant exposure to ASMs was associated with a higher risk of developing asthma, although the magnitude was more modest than previously reported. Clinicians should carefully weigh the benefits of prescribing ASMs to children, accompanied by subsequent close monitoring for any clinically relevant safety signals.

Need to study simplification of gastrointestinal medication regimen in cystic fibrosis in the era of highly effective modulators.

The success of highly effective modulator therapy (HEMT) has led to consideration of simpler regimens for people with CF (PwCF) with opportunities to modify burdensome regimens. Despite the intuitive appeal of discontinuing chronic therapies no longer necessary, this process should be pursued systematically to ensure safety, adherence, and validate patient-centered preferences. We designed a questionnaire to determine the state of use of acid-suppressive medications (ASM) and pancreatic enzyme therapy (PERT), current self-withdrawal and provider-directed withdrawal practices, and interest in a standardized withdrawal study. In collaboration with CF Foundation (CFF), a questionnaire was developed and distributed to members of Community Voice (CV, comprised of PwCF and their loved ones), and CF providers regarding the need to study simplifying the gastrointestinal (GI) regimen for PwCF on HEMT. Approximately 20-40% of CV or CF providers have decreased or stopped ASM for those on HEMT. For PERT, CV and CF providers have decreased dose (34%-48% and approximately 25%, respectively) more often than having stopped it altogether (13%-24% and 3%-12%, respectively). Cumulatively, there is interest in pursuing research in this area (86% CV and 89% CF providers) and willingness to enroll in such a study (80% CV and 89% CF providers). Systematically studying the withdrawal of common GI medications, ASM and PERT, is important to CV and CF providers. Decreases in dosing and withdrawal are already taking place without evidence to support this practice. This questionnaire is the first step in designing a GI medication simplification study in PwCF on HEMT.

Evaluation of factors affecting epidermal growth factor receptor tyrosine kinase inhibitor-induced hepatotoxicity in Japanese patients with non-small cell lung cancer: a two-center retrospective study

BackgroundGefitinib and erlotinib, are epidermal growth factor receptor tyrosine kinase inhibitors, and are currently recommended for non-small cell lung cancer stage IV in the elderly and in patients with decreased performance status in the Japanese Lung Cancer Society Guideline, but they occasionally caused severe hepatotoxicity requiring postponement or modification of treatment. However, little is known about the risk factors for hepatotoxicity in patients receiving gefitinib and erlotinib. In this study, we investigated the factors influencing hepatotoxicity in Japanese non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib monotherapy.MethodsJapanese patients with NSCLC who started gefitinib or erlotinib monotherapy from January 2005 to December 2017 at Kanazawa University Hospital or Kanazawa Medical University Hospital were included in this study. Factors affecting hepatotoxicity were retrospectively investigated by multiple logistic regression analysis.ResultsA total of 102 patients who received gefitinib and 95 patients who received erlotinib were included in the analysis. In the gefitinib group, a body mass index (BMI) ≥ 25 was associated with an increased risk of hepatotoxicity (OR = 4.571, 95% CI = 1.486–14.056, P = 0.008). In the erlotinib group, concomitant use of acid-suppressing medications (AS), namely proton pump inhibitors or histamine-2 receptor antagonists, was associated with a reduced risk of hepatotoxicity (OR = 0.341, 95% CI = 0.129–0.900, P = 0.030).ConclusionsBMI ≥ 25 in patients treated with gefitinib increased the risk of hepatotoxicity. In contrast, AS combination with erlotinib reduced the risk of hepatotoxicity. Thus, because different factors influence the risk of hepatotoxicity, monitoring for adverse events should take into account patient background factors and concomitant medications.

The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial.

Probiotics contain living microorganisms consumed for their putative benefits on the intestinal microbiota and general health and a concept is emerging to use probiotic as a therapeutic intervention to reduce proton pump inhibitors (PPIs) negative effects, but data is lacking. The use of PPIs can result in disordered gut microbiota, leading to a risk of enteric infections. PPIs are frequently prescribed in the general practice setting for gastroesophageal reflux disease (GERD), peptic ulcer disease, and related conditions. Despite the availability and widespread use of probiotics and acid-suppressing medications, the effect of PPIs-induced gastric acid suppression on the survival and colonization of probiotics bacterial species is currently unclear. We hypothesized that gastric acid suppression may improve intestinal colonization of probiotics bacterial species and probiotic intervention may have a potential role in mitigating untoward effects of PPI. In a randomized, double-blind, placebo-controlled study, healthy subjects were given either proton pump inhibitor (PPI, n=15) or placebo (n=15) over 6 weeks. All subjects then consumed multi-strain probiotics from weeks 2-6. Thirty participants (10 males, 20 females, age range: 18-56 years) were enrolled in the study. Shotgun metagenomic sequencing and untargeted metabolomics analyses were performed on stool samples collected at week 0, 2, and 6. Short term PPI treatment increased the microbial abundance of Streptococcaceae (p=0.004), Leuconostacaceae (p=0.001), and Pasteurellaceae (p=0.020) at family level and corresponding genus levels. The metabolomic analysis of the stools revealed a change in 10 metabolites where Gly Arg Val and phenylacetic acid were consistently increased compared to the baseline. Probiotic intervention inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p=0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. Notably, PPI enhanced the colonization of certain probiotic bacterial species like Streptococcus thermophilus (p<0.05) along with other species present in the multi-strain probiotic. Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations. CLINICAL TRIALS. NCT03327051.

Loosening the belt on magnetic sphincter augmentation indications: does body mass index matter?

Magnetic sphincter augmentation (MSA) is an effective treatment for gastroesophageal reflux disease (GERD). However, the impact of obesity on MSA outcomes is unknown. The objective of this study was to evaluate the effectiveness of MSA in patients with GERD and obesity. A retrospective cohort study was performed of consecutive patients who underwent laparoscopic MSA at three high-volume centers from 2016 to 2019. Patients were grouped into four cohorts according to the World Health Organization body mass index (BMI) classification: BMI < 25 (normal weight), BMI 25-29.9 (overweight), BMI 30-34.9 (obese class I), and BMI > 35 (obese class II-III). Preoperative, operative, and postoperative data were compared between groups. A total of 621 patients underwent laparoscopic MSA during the study period. Follow-up with endoscopy or video esophagram was available for 361 patients (58%) with a median follow-up of 15.4months. Baseline characteristics of the groups were similar except the BMI > 35 group had more females and a higher preoperative median DeMeester score. There were no significant differences in outcomes between normal weight, overweight, and obese patient groups undergoing MSA. All groups experienced significant reductions in acid suppressive medication use, low GERD-HRQL scores, low DeMeester scores, few intraoperative and postoperative complications, and low rates of hiatal hernia recurrence after MSA. Magnetic sphincter augmentation is safe and effective in improving GERD symptoms, reducing esophageal acid exposure, and preventing hiatal hernia recurrence, irrespective of patient BMI. MSA should be considered an acceptable treatment option for obese patients with GERD.

Gastrointestinal Factors Associated With Hospitalization in Infants With Cystic Fibrosis: Results From the Baby Observational and Nutrition Study.

To identify factors that increase the risk of gastrointestinal-related (GI-related) hospitalization of infants with cystic fibrosis (CF) during the first year of life. The Baby Observational and Nutrition Study was a longitudinal, observational cohort of 231 infants diagnosed with CF by newborn screening. We performed a post-hoc assessment of the frequency and indications for GI-related admissions during the first year of life. Sixty-five participants had at least one admission in the first 12 months of life. High pancreatic enzyme replacement therapy (PERT) dosing (>2000 lipase units/kg per meal; hazard ratio [HR] = 14.75, P = 0.0005) and use of acid suppressive medications (HR = 4.94, P = 0.01) during the study period were positively associated with subsequent GI-related admissions. High levels of fecal calprotectin (fCP) (>200 μg/g) and higher relative abundance of fecal Klebsiella pneumoniae were also positively associated with subsequent GI-related admissions (HR = 2.64, P = 0.033 and HR = 4.49, P = 0.002, respectively). During the first 12 months of life, participants with any admission had lower weight-for-length z scores (WLZ) (P = 0.01). The impact of admission on WLZ was particularly evident in participants with a GI-related admission (P < 0.0001). Factors associated with a higher risk for GI-related admission during the first 12 months include high PERT dosing, exposure to acid suppressive medications, higher fCP levels, and/or relative abundance of fecal K pneumoniae early in life. Infants with CF requiring GI-related hospitalization had lower WLZ at 12 months of age than those not admitted as well as those admitted for non-GI-related indications.

Phosphorus bioaccessibility measured in four amino acid–based formulas using in-vitro batch digestion translates well into phosphorus bioavailability in mice

ObjectiveThe aim of this study was to quantify the bioaccessibility of phosphorus from amino acid–based formulas (AAFs) under different digestive conditions. MethodsWe developed in-vitro batch digestion models with stomach digestion at different pH mimicking the normal digestive condition and conditions representing use of acid-suppressive medication. To validate bioaccessibility findings, we devised a low phosphorus murine model to test phosphorus bioavailability under compromised digestive conditions using proton pump inhibitors (PPIs) to neutralize stomach pH. ResultsIn vitro phosphorus bioaccessibility of AAFs Neocate® Infant and Neocate Junior ranged between 57% and 65% under normal digestive conditions for infants (stomach pH 3.5) and between 38% and 46% under conditions that simulated bypass of stomach acidification, which is comparable to control diet and two EleCare® AAFs. In vivo bioavailability analysis showed that both Neocate formulas were able to normalize plasma phosphorus levels when administered to low phosphorus mice along with PPIs (control diet + PPI 8 ± 0.4; Neocate Infant 10.1 ± 0.9; Neocate Junior 9.2 ± 0.6; EleCare Infant 8.6 ± 0.4; EleCare Junior 8.7 ± 0.5; n = 8–10; P < 0.0001 versus baseline 3.4 ± 0.2 mg/dL). In comparison, plasma phosphorus levels remained lower on the low phosphorus diet (5.7 ± 0.2 mg/dL). Furthermore, urinary phosphorus/creatinine and intact fibroblast growth factor 23 were significantly lowered by low phosphorus diet. In contrast, intact parathyroid hormone and 1,25-dihydroxy vitamin D decreased and increased, respectively, and these parameters likewise normalized in mice administered AAFs. ConclusionThe present findings indicated that phosphorus bioaccessibility in the in-vitro batch digestion model translates well into phosphorus bioavailability in mice even under compromised digestive conditions that bypass gastric acidification.

Safety and efficacy of an implantable device for management of gastroesophageal reflux in lung transplant recipients.

BackgroundMagnetic sphincter augmentation (MSA) is a promising minimally invasive surgical technique for management of gastroesophageal reflux disease (GERD); however, device implantation after transplantation has not been studied and may be concerning in these immunosuppressed patients. We explored the safety of the LINX Reflux Management System (MSA device) for management of GERD following lung transplantation (LTx).MethodsLung transplant recipients who underwent LINX implantation at our institution between 2017 and 2019 were followed prospectively in the Reflux Following Lung Transplantation and Associated Treatment Registry. Ambulatory pH testing and acid-suppressing medication use were compared before and after LINX implantation. One-year outcomes and change in pulmonary function were compared between matched LINX and fundoplication groups.ResultsOf 17 patients who underwent post-lung transplant LINX implantation, 8 (47.1%) agreed to undergo post-LINX pH testing. Three/eight (37.5%) patients achieved normal esophageal acid exposure time; 14 (82.4%) remained on acid-suppressing medication at one-year under the direction of their transplant teams. One-year patient survival and change in pulmonary function were similar between groups. LINX patients experienced more early side effects.ConclusionsUse of the LINX MSA device in a cohort of lung transplant recipients at our institution was associated with similar short-term safety compared to traditional fundoplication, however assessment of efficacy was limited. Further investigation is needed to characterize the long-term efficacy of LINX implantation after LTx.

Reflux Control After Barrett’s Esophagus Ablation

Esophageal adenocarcinoma (EAC) is difficult to treat and carries a poor prognosis. Barrett’s esophagus, which develops from long-standing gastroesophageal reflux disease, is the only known precursor to EAC. Endoscopic eradication therapy is a major advancement in the treatment of dysplastic Barrett’s esophagus and early EAC; however, failure to eradicate disease and a high rate of recurrence with risk of progression currently remain unacceptably high with the use of acid suppressive medication for reflux. Herein, we describe the physiology of gastroesophageal reflux and review the current literature on endoscopic eradication therapy for Barrett’s esophagus. We summarize that antireflux surgery for reflux control as an adjunct to endoscopic eradication therapy may decrease the need for multiple endoscopic sessions (to achieve eradication), decrease the risk for recurrence/progression, and potentially decrease the need for surveillance.

Proton pump inhibitor usage reduces sustained viral response rates for veterans with HIV/HCV coinfection on ledipasvir/sofosbuvir: a real-world study from a multicentre VA cohort.

Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with HIV/HCV coinfection, where concomitant antiretrovirals may result in more complex drug interactions. This retrospective study evaluates the effects of acid suppression medications (PPI or H2 -receptor antagonist [H2 B]) use and SVR rates in patients with HIV/HCV or HCV and taking LDV/SOF in a large multicentre veteran cohort. Patients in the Veterans Affairs Health Care System who received LDV/SOF ± ribavirin from 10/10/2014 to 12/31/2015 were included. The odds ratios (OR) of PPI or H2 B use for SVR were adjusted for clinical factors and with inverse probability of treatment weighting for non-random treatment selection for acid suppression medication use. There were 9703 veterans included in our final analysis. After adjustment of other clinical factors, PPI use is associated with a lower SVR in the overall cohort (95.0% vs. 96.1%, OR: 0.86, 95% CI: 0.74-0.99, p=.03, number needed to harm 90.9) and HIV/HCV coinfection subgroup (93.4% vs. 96.9%, OR: 0.47, 95% CI: 0.26-0.85, p=.01, number needed to harm 28.6). This present study reveals PPI use is associated with reduced SVR after LDV/SOF treatment, with a more significant impact in the subgroup of patients with HIV/HCV coinfection. Precautions need to be taken when using PPI and LDV/SOF in this group of patients.

The impacts of acid suppression on duodenal microbiota during the early phase of severe acute pancreatitis

Duodenal dysbiosis may be potential infection risks in patients with severe acute pancreatitis (SAP). Acid-suppression drugs (ACDs) are widely used in SAP patients in Asian countries. However, the impact of ACDs on duodenal microbiota during the early phase of SAP is still unknown. This randomized controlled clinical trial evaluated the impacts of esomeprazole (Eso), one of ACDs on duodenal microbiota during the first week of SAP with duodenal aspirates culture and 16sRNA Illumina sequencing analysis. 66 patients were randomized as 1:1 ratio into Eso group (Eso 40 mg/day) and Eso-N group (no Eso). The occurrence of duodenal bacterial overgrowth (DBO) was significantly higher in Eso group (about 85%) than that in Eso-N group (about 42%). The duodenal microbiota of the SAP patients shifted away from that of the normal control. There were differences between the Eso-N and Eso groups including enriched abundances of the class Negativicutes, order Selenomonadales and genus Veillonella. Acid suppression significantly increased incidence of Candida oesophagitis (CE) by 8-folds but did not increase other infectious events. In conclusion, acid suppression greatly increased the occurrence of DBO, duodenal dysbiosis and CE during the first week of SAP. Restrictive use of acid-suppressing medications might be helpful to reduce CE and potential risk of pancreatic infection in SAP patients.Trial registration: Chictr.org, ChiCTR-IPR-16008301, Registered April 18 2016, http://www.chictr.org.cn/showproj.aspx?proj=14089.

Use of anti-reflux medications in infants under 1 year of age: a retrospective drug utilization study using national prescription reimbursement data

Non-specific symptoms such as irritability, vomiting, and back arching during the infant period are often attributed to gastroesophageal reflux. While numerous studies have shown no significant benefit to the use of acid suppressant medications in this population, these medications are frequently prescribed in response to these symptoms. Our goals were to understand how often children were being prescribed this medication. To do this, data was extracted from a national database for reimbursement of prescribed medications through the General Medical Services scheme (GMS). Infants aged less than 1 year and eligible for reimbursement under GMS were included for analysis. A total of 450 infants per 10,000 eligible population received an anti-reflux preparation from the following drug classes (H2 antagonists, proton pump inhibitors, or alginate preparations) in 2018. This is compared with that in 2009 where only 137 per 10,000 eligible infants received these medications. This increase was predominantly attributable to an increase in ranitidine prescriptions.Conclusion: Despite a change in clinical guidelines, anti-reflux preparations are increasingly being prescribed to infants aged less than 1 year. The reasons behind the increase in prescriptions containing these medications cannot be ascertained from this data. This may suggest a proportion of these prescriptions may be unwarranted in this population. What is Known: • The prescription of PPIs in infants has increased in a number of countries. • Use of anti-reflux medications has a very poor evidence base in infancy. What is New: • This data focuses only on an infant age group in a "well" cohort. • Ranitidine may contribute to increased acid-suppressant use in infancy.

S3292 Increased Admissions From Side Effects Reported With Therapeutic Use of Acid Suppression Medications: A Nationwide Inpatient Database Analysis of the Last Two Decades

INTRODUCTION: Increased awareness has been placed on potential side effects of Proton pump inhibitors (PPIs) and its safety profile due to publication bias towards retrospective studies showing potential associations. The International Classification of Diseases (ICD) coding of drug adverse effects yields valuable evidence. We aimed to quantify and analyze the trends in documentation of the admissions related to acid suppression medication adverse effects. METHODS: We utilized the National Inpatient Sample Database to analyze longitudinal trends related to all hospitalizations due to acid suppression medication causing adverse effects in therapeutic use (ICD-9 E943.0) between 1993 and 2014 in the US. Similar query was also made for antidiarrheal agents (ICD-9 E943.5) and laxatives (ICD-9 E943.2, E943.3). Trends in admission, discharge rates and payor were analyzed. RESULTS: The total number of reported admissions related to adverse effects of acid suppression medications nationwide were 1,009 with a discharge rate of 0.4 per 100,000 in 1993, which declined to 696 annual admissions and a discharge rate of 0.2 per 100,000 by 2003. An increase was observed until 2014, with 2,640 admissions and 0.8 discharge rate in 2014 (Figure 1). The number of admissions/years increased by 279% from 1993 to 2014. For admitted patients, average age was 65-84 years old, and 57.39% were females (Figure 2). Most of the discharges were covered under Medicare (52.3%), followed by private insurance (30.1%). In the year 2014, secondary diagnosis coded along with PPI adverse effects were chronic kidney disease, urinary tract infection, and fracture of unspecified bone. CONCLUSION: Our findings show that the number of admissions reported due to acid suppression medication adverse effects in the US has increased over the past two decades. This increase became prominent starting in the early 2000s, which coincides with the wider implementation of electronic medical records in the US. However similar trend was not observed in documentation of side-effects of anti-diarrheal agents and laxatives suggesting that the coding of adverse effects related to acid suppression medications might have been driven by publication bias of multiple studies showing associations of potential side effects related to these medications. Given recent updates with prospective studies showing well tolerance of these medications, outside of slightly increased risk of enteric infection, the accuracy of these codes should be evaluated.Figure 1.: Rate of Admission for Adverse Effects in Therapeutic Use.Figure 2.: Age Group Distribution of Admissions due to Adverse Effects of Acid Suppression Medication in Therapeutic Use in 2014.

Reducing the Use of Antacids in the Neonatal Intensive Care Unit

Goal Our global aim is to decrease the number of acid suppressants used in the Rainbow Babies and Children’s NICU. The specific aim is to implement guidelines on appropriate use of acid-suppressing medications to decrease use by 50% in patients without indications by March 2019. Introduction Reflux is a physiologic occurrence in infants; it is particularly more prevalent in preterm babies. Previously, histamine-2 receptor antagonists (H2As) or proton pump inhibitors (PPIs) have been used for symptomatic reflux, apnea/bradycardia/desaturations, or irritability. Recent studies have shown, …

P-371 The use of gastric acid suppression in surgical oncology patients

The use of gastric acid suppression medications during oncologic surgery has become a mainstay within the perioperative period. Recent literature suggests that the use of these medications may be associated with significant adverse effects, including an increase in post-operative infections. However, surgical oncology patients have never been particularly studied and the impact of acid suppression in this cohort is generally unknown. We intended to compare the rates of postoperative morbidity including various types of infections and organ dysfunction in cancer patients who take acid-suppressing medications versus those who are not taking said medications during their surgical course.

Acid-suppressive medications and risk of colorectal cancer: results from three large prospective cohort studies

BackgroundDespite several plausible biological mechanisms linking proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) with colorectal tumorigenesis, their association with risk of colorectal cancer (CRC) has not been adequately assessed in prospective epidemiological studies.MethodsWe evaluated the association of acid-suppressive medication use with CRC risk among 175,871 (PPI) and 208,831 (H2RA) participants from three large prospective cohort studies. Medication use was assessed at baseline and updated biennially. The association was evaluated using multivariate Cox proportional hazards regression models.ResultsThere was no significant association between baseline PPI use (hazard ratio (HR) = 0.89, 95% confidence interval (CI), 0.71–1.12) or PPI use after a lag of 8–10 years (HR = 1.12, 95% CI, 0.78–1.59) with CRC risk. We observed no significant association between H2RA use after a lag of 8–10 years and CRC risk (HR = 1.02, 95% CI, 0.81–1.28), while risk was lower for participants with baseline H2RA use (HR = 0.76, 95% CI, 0.60–0.95). Duration of PPI use or H2RA use was not associated with CRC risk (P-trend = 0.21 and 0.95, respectively).ConclusionsAmong participants from three large prospective cohorts, use of PPI or H2RA was not associated with higher risk of colorectal cancer.

Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia.

Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30-2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22-2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3-6months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22-3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83-3.66). We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.