Acid suppressants reduce the therapeutic effect of immune checkpoint inhibitors and increase the risk of acute kidney injury: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy; however, they can lead to immune-related adverse events (irAEs) through immune function of patients. Therefore, this meta-analysis aimed to assess the concomitant effect of acid suppressants (ASs) on ICIs, including several subgroup analyses. METHODS: We identified related studies and generated the forest plot. The primary endpoint was defined as the change in progression free survival (PFS) and overall survival (OS) with or without ASs administration. We also evaluated the effect of ASs on the incidence of irAEs. RESULTS: The total hazard ratio (HR) of ASs on PFS with ICI treatment was 1.39 and the 95% confidence interval (95% CI) was 1.21-1.59 (Z: p < 0.00001). Moreover, the total HR of ASs on OS was 1.40 and the 95% CI was 1.21-1.61 (Z: p < 0.00001), suggesting that ASs reduced ICI's therapeutic effect. The total odds ratio (OR) for evaluating the effect of ASs on irAEs was 1.23 with a 95% CI of 0.81-1.88 (Z: p = 0.34). However, ASs significantly worsened acute kidney injury (AKI) (total OR 2.10; 95% CI 1.74-2.53 (Z, p < 0.00001)). Furthermore, although proton pump inhibitors (PPIs) reduced ICI's therapeutic effect, histamine H2-receptor antagonists (H2RAs) did not affect OS. CONCLUSIONS: It was shown that ASs, especially PPIs, reduced ICI's therapeutic effect, while H2RAs had no effect, and ASs did not affect irAEs; however, it is a risk factor for ICIs-induced AKI.

Impact of proton pump inhibitor management committee's multifaceted interventions on acid suppressant prescribing patterns in outpatient and emergency departments.

BACKGROUND: A nationwide campaign for rational proton pump inhibitor (PPI) use launched in 2015 had a positive impact for hospitalized patients PPI use. But there were few studies focusing on the rational use of PPIs in outpatients. In 2018, the PPI management committee conducted a year-long intervention on the appropriate use of PPIs in outpatient and emergency departments, including clinical pharmacist interventions and stewardship interventions. The purpose of this study was to examine the impact of the PPI management committee's multifaceted interventions by comparing the real-world acid suppressant prescribing patterns for outpatients before (2017) and after intervention (2019) at a Chinese tertiary teaching hospital. METHODS: Prescriptions containing any acid suppressant in outpatient and emergency departments in baseline (2017) and postintervention (2019) periods were extracted from the hospital information system and the prescription automatic screening system. Acid suppressant prescribing patterns were evaluated based on primary diagnoses and patient demographics. The prescribed acid suppressants stratified using age groups (< 7, 7-17, 18-45, 46-65, 66-85 and > 85 years) were also examined. RESULT: The utilization rate of acid suppressant in 2017 and 2019 was 2.5% (41,165/1,619,366) and 2.2% (49,550/2,236,471), respectively (P < 0.0001). 60,135 acid suppressant prescriptions were obtained in 2017 and 73,275 in 2019. The rate of acid suppressant prescriptions for the approved indications significantly increased from 62.6% (2017) to 65.4% (2019) (P < 0.0001). Prescriptions diagnosed as abnormal symptoms, signs and clinical manifestations, decreased in 2019 (13.0% vs. 16.5%, P < 0.0001). The most frequently prescribed PPIs differed between 2017 and 2019 (rabeprazole 2017 vs. esomeprazole 2019). Omeprazole was the most common PPI and cimetidine was the most common H2RA prescribed to patients aged < 18 years in 2017 and 2019. A total of CNY11.83 million was spent on acid suppressants in 2019, accounting for about 48.7% of total medication cost, increased by 11.3% from 2017 (37.4%). CONCLUSION: The proportion of acid suppressant prescriptions for approved indications was enhanced after the PPI management committee's multifaceted interventions, but there were still some problems in the selection of acid suppressants.

Use of Acid-Suppressant Medications After Diagnosis Increases Mortality in a Subset of Gastrointestinal Cancer Patients.

BACKGROUND: Acid-suppressant medications, including proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs), are frequently prescribed and have been linked to increased risk of some gastrointestinal cancers. AIMS: We examined whether post-diagnosis use of PPIs/H2RAs is associated with the risk of mortality in gastrointestinal cancer patients. METHODS: We used data from patients with esophageal cancer, gastric cancer, or hepatocellular carcinomas (HCCs) in the national VA Central Cancer Registry diagnosed between 2002 and 2016. We identified PPI/H2RA prescriptions that were filled before and after cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3-month lag to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between the date of cancer diagnosis and the start of follow-up. RESULTS: PPIs were used by the majority (54% post-diagnosis use) of patients. We found no association between post-diagnosis PPI use and cancer-specific mortality in esophageal adenocarcinoma (HR 0.93; 95% CI 0.84-1.02), esophageal squamous cell carcinoma (HR 0.99; 95% CI 0.87-1.12), or gastric cardia cancer (HR 1.04; 95% CI 0.89-1.22) patients. Post-diagnosis PPI use was, however, associated with the increased risk of cancer-specific mortality for patients with gastric non-cardia cancer (HR 1.50; 95% CI 1.29-1.74) and HCC (HR 1.31; 95% CI 1.23-1.40). The results were similar for associations with post-diagnosis use of H2RAs. There was no association with pre-diagnosis PPI/H2RA use. CONCLUSION: Post-diagnosis PPI/H2RA use was associated with the increased mortality in gastric non-cardia cancer and HCC patients.

Use of proton pump inhibitors and risk of iron deficiency: a population-based case-control study.

BACKGROUND: Hypochlorhydric states are an important cause of iron deficiency (ID). Nevertheless, the association between therapy with proton pump inhibitors (PPIs) and ID has long been a subject of debate. This case-control study aimed to investigate the risk of ID associated with the use of PPIs using the UK Clinical Practice Research Datalink (CPRD) database. METHODS: Cases were patients aged 19 years or older with first-time diagnosis of ID between 2005 and 2016 (n = 26 806). The dates of first diagnosis of ID in cases defined the index dates. For each case, one control was matched by age, gender and general practice. A PPI "full" user (PFU) was defined as a subject who had received PPIs for a continuous duration of at least 1 year prior to the index date. A PPI "limited" users (PLU) was a subject who intermittently received PPI therapy. A PPI non-user (PNU) was a subject who received no PPI prescriptions prior to the index date. The odds ratio of ID in PFU and PLU compared to PNU was estimated using conditional logistic regression. RESULTS: Among cases, 2960 were PFU, 6607 PLU and 17 239 PNU. Among controls, 1091 were PFU, 5058 PLU and 20 657 PNU. Adjusted odds ratio of ID in PFU and PLU compared to PNU was 3.60 (95%CI, [3.32-3.91]) and 1.51 (95% CI, [1.44-1.58]). Positive dose-response and time-response relationships were observed. CONCLUSIONS: Chronic PPI use increases the risk of ID. Physicians should consider this when balancing the risks and benefits of chronic PPI prescription.

Prenatal, intrapartum, and postnatal factors are associated with pediatric eosinophilic esophagitis.

BACKGROUND: Multiple lines of evidence point to the potential importance of early-life environmental factors in the rapid increase in the incidence of eosinophilic esophagitis (EoE), but potential exposures have not been extensively studied. OBJECTIVE: We sought to assess the association between prenatal, intrapartum, and postnatal factors and the development of pediatric EoE using a case-control study. METHODS: Patients with EoE were recruited from an existing registry at Cincinnati Children's Hospital Medical Center (CCHMC). Population-based community control subjects were identified from a separate CCHMC registry. Mothers of study subjects were contacted and completed a Web-based questionnaire. Crude and adjusted models were used to estimate associations. RESULTS: Mothers of 127 cases and 121 control subjects were included. We observed a positive association between several early-life factors and EoE, including prenatal (maternal fever: adjusted odds ratio [aOR], 3.18; 95% CI, 1.27-7.98; preterm labor: aOR, 2.18; 95% CI, 1.06-4.48), intrapartum (cesarean delivery: aOR, 1.77; 95% CI, 1.01, 3.09), and infancy (antibiotic use: aOR, 2.30; 95% CI, 1.21-4.38; use of an acid suppressant: aOR, 6.05; 95% CI, 2.55-14.40) factors. We observed an inverse association between having a furry pet in infancy and EoE (aOR, 0.58; 95% CI, 0.34-0.97). No associations were observed for breast-feeding or maternal multivitamin or folic acid supplement use. CONCLUSION: Early-life factors, including maternal fever, preterm labor, cesarean delivery, and antibiotic or acid suppressant use in infancy, were associated with risk of pediatric EoE; having a pet in the home was protective. These results add to growing evidence that implicate early-life exposures in EoE pathogenesis.

A Nationwide Population-Based Cohort Study of Dementia Risk Among Acid Suppressant Users.

OBJECTIVE: Data regarding the potential link between acid suppressant use and dementia are inconsistent. This study assessed the association between cumulative exposure to proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) and dementia risk among Korean adults. DESIGN AND METHODS: A population-based longitudinal study was conducted using the Korean National Health Insurance Corporation claims database merged with national health examination data for 2002-2013. The study cohort included 70,529 subjects who were dementia-free in 2007. Incident dementia was assessed throughout follow-up until 2013. Exposure to acid suppressants prior to 2007 was assessed using a standardized defined daily dose system. Potential associations between acid suppressant use and dementia risk were analyzed using time-dependent Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 1,297 cases of dementia during the study period. Multivariate analyses identified several factors associated with dementia risk: old age, female, current smoker, Type 2 diabetes, comorbidities, and use of nonaspirin nonsteroidal anti-inflammatory drugs. H2RA users had a significantly increased risk of dementia compared with non-H2RA users (HR 1.31, 95% CI 1.13-1.51), whereas PPI use was not associated with increased risk. CONCLUSION: Our results indicate that exposure to H2RAs (but not PPIs) is associated with increased dementia risk. Further randomized controlled trials and basic research examining the underlying mechanism are needed to confirm this association.

Renal dysfunction in routine proton-pump inhibitor use may be linked to comorbidities: A real-world observational study.

INTRODUCTION: The use of proton-pump inhibitors (PPI) is linked with infrequent but serious adverse events, including acute kidney injury, chronic kidney disease (CKD) and progression of CKD. Data on renal safety in routine use of PPI are more relevant to clinical practice. We studied whether such use of PPI is associated with renal dysfunction. METHODS: Patients taking PPI for at least six weeks had serum creatinine tested pre (n = 200) and post (n = 180) recruitment. These patients were then advised to follow-up: those taking PPI for at least 90 days in the next six months (n = 77) and at least another 90 days in the following six months (n = 50), had serum creatinine tested at such follow-up. Renal dysfunction was defined as any increase in serum creatinine level above baseline. RESULTS: The 200 patients recruited had mean age 39.6 (SD 9.2) years. Ninety-eight (49%) patients had a history of previous PPI use (median six months; interquartile range [IQR] 3-24). Only 20 (11.1%) patients at six weeks, 11 (14.3%) at six months and six (12%) at one year had increase in creatinine level; a majority of them had less than 0.3 mg/dL increase. Ten of these 20 (six weeks), five of 11 (six months) and five of six (one year) had other risk factors for renal dysfunction. No patient developed CKD during the study period. CONCLUSIONS: Mild and non-progressive increase in serum creatinine occurred in 10% to 15% of patients on routine PPI use. A majority of them had other risk factors. Small sample size and short follow-up duration are a few limitations of this study.

Study on Nocturnal Infant Crying Evaluation (NICE) and Reflux Disease (RED).

BACKGROUND: Nocturnal infant crying is often empirically treated with acid suppressants. The aim of this study was to evaluate the prevalence and characteristics of gastroesophageal reflux (GER) in infants with unexplained persistent crying. METHODS: We enrolled all infants (0-12 months) referred for suspected GER disease who underwent esophageal impedance-pH monitoring (MII-pH) for unexplained persistent crying not improved by parental reassurance, dietary modification or alginate. Gastrointestinal malformation/surgery, neurological impairment and infections were exclusion criteria. Demographic and anthropometric parameters, GER symptoms and questionnaires (I-GERQ-R) and MII-pH data were recorded and analyzed. Normal MII-pH was defined when acid exposure was <3%, symptom index was <50% and symptom association probability was <95%. Acid exposure >5% and >10% was also considered. Statistical analysis was performed using Chi-Square and univariate and multivariable regression analysis. RESULTS: We included 50 infants (median age 3.5 months) who fulfilled the study criteria: 30 (60%) had normal MII-pH. I-GERQ-R score was abnormal in 33 (66%) infants, and 21/33 (64%) had normal MII-pH (p = 0.47). In the 26 (52%) infants with nocturnal crying, MII-pH was normal in 16 (54%) (p = 0.82). Associated regurgitation (>3 or >10 episodes/die) did not predict abnormal MII-pH (p = 0.74, p = 0.82, respectively). Univariate and multivariable regression analysis did not identify any clinical variable significantly associated with abnormal MII-pH. CONCLUSIONS: Infants with persistent unexplained and nocturnal crying should not be empirically treated with acid inhibitors.

Gastric pH and serum gastrin concentration in age-matched healthy dogs and dogs with chronic kidney disease.

BACKGROUND: Gastric hyperacidity and hypergastrinemia are purported to cause gastric ulceration in dogs with chronic kidney disease (CKD); however, no published studies have evaluated gastric pH with serum gastrin concentrations in dogs with CKD. HYPOTHESIS: To compare mean intragastric pH, mean percent pH distribution, and serum gastrin concentrations in dogs with CKD to age-matched, healthy dogs. We hypothesized there would be no difference in mean gastric pH or serum gastrin between groups. ANIMALS: Thirteen dogs with CKD; 10 aged-matched healthy dogs. METHODS: Prospective, case-control study. Serum chemistry, complete blood count, urinalysis, and serum gastrin concentrations were evaluated in all dogs before radiographic-assisted gastric placement of a pH capsule. Forty-eight-hour continuous gastric pH monitoring was performed in all dogs. Serum gastrin concentration, mean pH, and mean percentage time that gastric pH was strongly acidic (pH <1 and pH <2) were compared between groups using a repeated measures mixed-model ANOVA. RESULTS: No significant differences were observed between groups for any pH measurements, including mean ± SD gastric pH (CKD, 2.37 ± 0.87; healthy, 2.39 ± 0.99; P > .05). Serum gastrin concentrations were not significantly different between groups (median [range]: CKD, 10.5 ng/dL [<10-17.1]; healthy, 10.9 ng/dL [<10-15]; P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Our client-owned dogs with CKD did not have lower gastric pH or higher serum gastrin concentrations compared to healthy dogs. Our results suggest that prophylactic gastric acid suppression in dogs with CKD is not warranted unless other clinical indications for use are present.

Supportive treatment during the periprocedural period of endoscopic treatment for pancreatic fluid collections: a critical review of current knowledge and future perspectives.

Pancreatic fluid collections (PFCs) commonly develop as complications of acute pancreatitis and ductal disruption due to chronic pancreatitis. In the revised Atlanta classification, PFCs were classified based on the presence of necrosis and duration following the onset of acute pancreatitis. Interventions are required in cases of symptomatic pancreatic pseudocysts or walled-off necrosis (WON). In the management of these PFCs, endoscopic ultrasound-guided transluminal drainage and subsequent direct endoscopic necrosectomy for WON are increasingly utilized as less invasive treatment modalities compared to surgical debridement. To date, researchers have focused predominantly on the technical aspects of endoscopic therapy for symptomatic PFCs. Given the poor physical condition of patients receiving endoscopic treatment for PFCs, systemic support may have a substantial impact on the short- and long-term outcomes of these patients. A multidisciplinary approach is required to improve the clinical outcomes of patients with infected PFCs and their associated comorbidities. However, non-interventional support during the periprocedural period of endoscopic treatment of PFCs has not been fully discussed, and there have been considerable variations in the selection of treatment options between endoscopists and centers. To address these unmet needs in the clinical management of PFCs and promote future research to improve the clinical outcomes, we conducted a review of the literature within a multicenter consortium of expert endoscopists with specific expertise in the endoscopic treatment of PFCs. In this review, we summarize the current evidence on non-interventional supportive care (e.g., continuous lavage, medications, nutritional support, and antimicrobials) and propose potential topics for future research.

Evaluation of gastroprotectant administration in hospitalized cats in a tertiary referral hospital.

OBJECTIVES: The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats. METHODS: Pharmacy dispensation logs from an academic tertiary referral center were reviewed between 1 January 2018 and 31 December 2018. Cats that were administered proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, misoprostol, antacids or a combination were included. Data regarding medication, dosage, formulation, duration of administration, completeness of discharge instructions and clinical rationales for administration were obtained from medical records. The appropriateness of gastroprotectant use was assessed according to the American College of Veterinary Internal Medicine consensus statement guidelines. RESULTS: Of the 110 cases, 67 (60.9%) were prescribed a gastroprotectant medication without an appropriate indication. The most common reason for prescription was acute kidney injury in 26/67 (38.8%). PPIs were the most common gastroprotectant medication administered in 95/110 (86.3%) cats, followed by sucralfate in 18/110 (16.4%) and H2RAs in 11/110 (10%). Of the 35 cases in which gastroprotectant therapy was indicated, the medication chosen or dosage administered was considered suboptimal in 16 (45.7%). Instructions regarding the duration of administration, potential adverse effects and timing of administration in relation to meals or other medications were inconsistently provided in discharge instructions to pet owners. Of the 29 cases discharged with omeprazole, only 13 (44.8%) instructions included a duration of administration, while 6 (20.7%) recommended continuing gastroprotectants indefinitely until further notice, 16 (55.2%) discussed the timing of the administration in relation to a meal and six (20.7%) mentioned potential adverse effects; none advised tapering of omeprazole before discontinuation. CONCLUSIONS AND RELEVANCE: When prescribed, gastroprotectant medications were frequently prescribed injudiciously to cats in this referral population over a 12-month period. Discharge instructions to pet owners also often lacked information and recommendations regarding optimal administration, potential adverse effects, and tapering or discontinuation of the medications.

Childhood Acid Suppressants May Increase Allergy Risk-A Systematic Review and Meta-Analysis.

BACKGROUND: Recent studies suggest that the use of acid suppressants in early childhood may increase the risk of allergic diseases. OBJECTIVE: To systematically review and synthesize associations between the childhood use of acid suppressants and development of allergic diseases. METHODS: PubMed, Embase, The Cochrane Library, and Scopus were searched using a systematic search strategy. We included observational or interventional studies that looked at the use of acid suppressants in the pediatric population, in association with allergic outcomes such as asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and food allergies. Key data were extracted and risk of bias was evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, and heterogeneity was measured using I2. Further subgroup and sensitivity analyses were conducted. Overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework. RESULTS: This review included 5 observational studies from 1977 records with low-to-moderate risk of bias. Childhood acid-suppressant use was associated with significantly increased hazards of asthma (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.31-1.58), atopic dermatitis (HR = 1.12, 95% CI = 1.10-1.14), and allergic rhinitis (HR = 1.40, 95% CI = 1.24-1.58). These associations were adjusted for confounders such as demographics, parental educational level, and use of antibiotics. Overall quality of evidence was low. CONCLUSIONS: Childhood use of acid suppressants may increase the risk of incident asthma, atopic dermatitis, and allergic rhinitis. However, larger studies such as randomized controlled trials are needed to determine causality. These drugs should be used judiciously in pediatric patients, and more stringent guidelines should be advocated.

Reducing Unnecessary Acid Suppression Use in Hospitalized Patients: A Description of Targeted Strategies Implemented Across a Large Health System.

Background: Ensuring the appropriate use of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) is an important hospital patient safety and quality initiative because therapy may be inappropriately continued during transitions of care. In this article, we aim to describe the impact of targeted quality improvement strategies to reduce unnecessary acid suppression use in hospitalized patients across a large health system. Methods: Beginning January 1, 2018, focused quality improvement strategies to prevent unnecessary initiation and continuation of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) were implemented throughout a large health system. Targeted strategies were initially tested as part of the PPI deprescribing Institute for Healthcare Improvement (IHI) International Innovators Network initiative and were expanded to include H2RAs for hospitalized patients. Strategies to decrease PPIs and H2RAs during hospitalization included standardization of stress ulcer prophylaxis care pathways, evidence-based order set modifications, technology-driven support, and clinical pharmacy metric performance to goal. PPI/H2RA days of therapy (DOT) per 1000 patient days were measured from the first quarter (1Q) of 2017 to the fourth quarter (4Q) of 2021 to determine if implemented strategies resulted in improvement. Results: After quality improvement strategies were implemented, the number of PPI/H2RA DOT was reduced by 7.9 days per 1000 patient days each quarter over 4 years. The average PPI/H2RA DOT per 1000 patient days decreased from 592 (1Q 2017) to 439 (4Q 2021). In the fourth quarter of 2018, 45 hospitals (28%) achieved a 10% reduction in combined PPI/H2RA DOT per 1000 patient days, and 121 hospitals (97%) attained the goal of greater than 25% of eligible patients deprescribed PPI/H2RA for ICU patients in the fourth quarter of 2019. In the fourth quarter of 2020, 97 hospitals (87%) met the metric of 40% or more of eligible patients deprescribed from PPI/H2RA in or after an ICU stay, and 85 hospitals (87%) reached 50% or more of eligible patients deprescribed PPI/H2RA in or after an ICU stay in 4Q2021. Conclusion: Targeted quality improvement strategies decreased unnecessary PPI and H2RA use for a large health system over 4 years. Continually evaluating measured results along with establishing a new clinical pharmacy metric goal each year to encourage further improvement contributed to deprescribing success.

Evaluation of proton pump inhibitor administration in hospitalized dogs in a tertiary referral hospital.

BACKGROUND: Although proton pump inhibitors (PPIs) are commonly administered to hospitalized dogs, prescribing patterns and appropriateness of use require continued investigation. HYPOTHESIS/OBJECTIVE: Describe prescription patterns and appropriateness of use associated with PPIs in hospitalized dogs at a single tertiary care facility. We hypothesized that the majority of prescriptions would not comply with current guidelines for the rational use of acid suppressants. ANIMALS: Two hundred randomly selected hospitalized dogs. METHODS: Retrospective evaluation of the medical records associated with a randomly selected sample of hospitalized dogs that received PPIs between January 2013 and December 2018. RESULTS: A total of 12 610 dogs were admitted for first-time hospitalization between January 2013 and December 2018. Forty percent of these dogs (5062/12610) were prescribed a PPI PO or IV. Of the 200 randomly selected records, an adequate indication for use was identified in 27% of dogs (54/200). Of the dogs surviving to discharge, 54% (95/175) were discharged with a PPI and 51.6% (49/95) of those were prescribed an inadequate dose. CONCLUSIONS AND IMPORTANCE: Our findings support other studies in which the majority of PPI prescriptions for hospitalized dogs at a tertiary care hospital lacked an appropriate indication. Furthermore, analysis of the prescribing patterns of dispensed PPIs identified a frequent occurrence of dosages considered inadequate, raising concern for ineffective treatment even with appropriate indications of use. With growing concern of adverse effects associated with PPI and other acid suppressant administration in human and veterinary medicine, rational use of these medications following consensus guidelines should be emphasized and treatment should be reserved for dogs with historical, physical examination, clinicopathologic, and imaging findings supportive of an appropriate indication for use.

Infant Exposure to Acid Suppressant Medications Increases Risk of Recurrent Wheeze and Asthma in Childhood.

BACKGROUND: Acid suppressant medications (ASMs) are commonly prescribed in infancy. Little is known about the relationship between ASM exposure and risk of childhood asthma and atopic conditions. OBJECTIVE: We sought to examine the association between infant ASM exposure and risk for developing recurrent wheeze, allergen sensitization, and asthma in early childhood. METHODS: We used data from a diverse, multicenter, prospective cohort study of 921 infants with a history of bronchiolitis. ASM exposure (histamine-2 receptor antagonists and/or proton pump inhibitors) during infancy (age: <12 months) was ascertained by parent report and medical record review. The outcomes were recurrent wheeze by age 3 years, early childhood allergen sensitization (serum specific IgE), and asthma by age 6 years. We constructed multivariable Cox proportional hazards models and multivariable logistic regression models adjusting for multiple confounders. RESULTS: Of the 921 children in the cohort, 202 (22%) were exposed to ASMs during infancy. Compared with unexposed children, those exposed to ASM were more likely to develop recurrent wheeze by age 3 years (adjusted hazard ratio: 1.58, 95% confidence interval [CI]: 1.20-2.08, P = .001) and asthma by age 6 years (adjusted odds ratio: 1.66, 95% CI: 1.22-2.27, P = .001). ASM exposure during infancy was not significantly associated with the development of early childhood allergen sensitization (adjusted odds ratio: 1.00, 95% CI: 0.70-1.44, P = .99). CONCLUSIONS: Although exposure to ASMs during infancy does not increase the risk of allergen sensitization in early childhood, ASM exposure during infancy increases the risk of recurrent wheeze and asthma during early childhood.

Gastric acid suppressants and cognitive decline in people with or without cognitive impairment.

INTRODUCTION: Studies suggest associations between proton pump inhibitors (PPIs) and dementia risk; however, many neither considered histamine-2 receptor antagonists (H2RAs) nor baseline cognitive status. METHODS: Participants (National Alzheimer's Coordinating Center Database; 2005-2021) using a PPI or H2RA were compared. Covariate-adjusted Cox regression was used to estimate hazard ratios (HR) for progression from normal cognition to mild cognitive impairment (MCI), and from MCI to dementia over 5 years. In a propensity-score-matched subsample of mild-moderate Alzheimer's disease (AD), mixed-effects negative binomial regression was used to estimate decline in delayed recall memory. RESULTS: Compared to PPI, H2RA use was associated with earlier progression from MCI to dementia (HR = 1.40 [1.09-1.81]; n = 1701), and with faster memory decline in AD over time (rate ratio = 0.76 [0.64-0.92]; n = 628), but not with progression from normal cognition to MCI (HR = 0.94 [0.71-1.24]; n = 2784). DISCUSSION: Compared to PPIs, H2RAs were associated with cognitive decline, specifically among people with pre-existing cognitive impairment.

Occurrence of a Duodenal Polypoid Lesion During Long-Term Acid Suppression Therapy and Its Regression After Drug Discontinuation.

Formation of multiple fundic gland polyps or hyperplastic polyps in the gastric mucosa is one of the well-known adverse effects of the long-term acid suppression therapy for peptic ulcer disease. However, similar phenomenon has not been reported to occur in the duodenum. We report a case of duodenal polypoid lesion that developed after the long-term use of acid suppressants and disappeared after the cessation of the treatment. The patient was a 76-year-old man with a history of heavy cigarette smoking and excessive alcohol intake who had been treated with medication of gastric acid suppressants, including proton pump inhibitors and potassium-competitive acid blockers, for refractory gastroesophageal reflux disease. After receiving the acid suppression therapy for 3 years, a polypoid lesion of 10 mm in diameter was found at the portion of the duodenal bulb. This polypoid lesion disappeared 1.5 months after the cessation of treatment. We hypothesized that changes in serum gastrin levels caused by acid suppression therapy might have been associated with the development and regression of the duodenal polypoid lesion.

Gastroprotective Therapy.

A range of gastroprotective drugs are available for the treatment of esophagitis and gastroduodenal mucosal injury including acid suppressants (ie, histamine-2 receptor antagonists, proton pump inhibitors), coating agents, prostaglandin analogs, and antacids. Of these, the proton pump inhibitors are the most effective drugs for the medical treatment of upper gastrointestinal injury. However, proton pump inhibitors are not effective for all causes of upper gastrointestinal injury. The choice of gastroprotective drug should be guided by the cause and location of gastrointestinal injury and the potential for adverse effects.

The Risk of Epilepsy after Long-term Proton Pump Inhibitor Therapy.

BACKGROUND: Prescription-event monitoring studies have reported incident epilepsy or seizures in proton pump inhibitor (PPI) recipients. We examined the risk of epilepsy after prolonged PPI exposure and determine what age group was at higher risk of epilepsy. METHODS: We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000). PPI users with subsequent epilepsy were selected as the case cohort. Controls were PPI users without subsequent epilepsy, matched for age, sex, PPI use indication, enrollment time, end point time, follow-up period, overall systemic health, and comorbidities. The total dose of PPI was defined as the cumulative defined daily dose (cDDD). Prolonged PPI use was defined as a cDDD > 365. A logistic regression analysis was performed. Population attributable risk was calculated. RESULTS: Epilepsy occurred 4.13 years after the initiation of PPI use. PPI users with the highest risk of incident epilepsy received a cDDD > 365 [odds ratio = 1.63, 95% confidence interval = 1.37-1.95], followed by 121-365 cDDD (1.33, 1.18-1.51) and 31-120 cDDD (1.15, 1.02-1.29), compared to those receiving a cDDD ≤ 30, after adjusting for potential confounders. Prolonged PPI use increased the risk of epilepsy in all age groups, and the risk was highest for those older than 80 years (3.11, 1.67-5.79). The population attributable risk was 12.2% (> 365 cDDD vs ≤ 30 cDDD). DISCUSSION: Prolonged PPI therapy was associated with an increased risk of epilepsy, particularly in the elderly population.