Use Of Pump Inhibitors Research Articles

578. DUPILUMAB EFFICACY IN EOSINOPHILIC OESOPHAGITIS PATIENTS TREATED WITH PRIOR THERAPY AND INADEQUATE RESPONSE, INTOLERANCE, OR CONTRAINDICATION TO SWALLOWED TOPICAL CORTICOSTEROIDS

Abstract Background Improvements in histologic, symptomatic, and endoscopic aspects of eosinophilic oesophagitis (EoE) were observed in patients treated with dupilumab weekly (qw) enrolled in the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), regardless of prior inadequate response, intolerance, and/or contraindication to swallowed topical corticosteroids (STC). Here we assess the efficacy of dupilumab qw versus placebo in this STC non-responsive/intolerant subgroup, stratifying further by those with/without history of food elimination diets, proton pump inhibitor (PPI) use at randomisation, or history of oesophageal dilation. Methods This analysis includes patients who received dupilumab 300 mg qw or placebo for 24 weeks in Part B and an additional 28 weeks dupilumab in Part C. Co-primary endpoints (Weeks 24 and 52) include: proportions of patients achieving peak eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Secondary endpoints assessed included proportions of patients achieving PEC ≤1 eos/hpf, <15 eos/hpf, % change in PEC, and absolute change in Endoscopic Reference Score, and EoE-Histologic Scoring System grade/stage scores. Results Dupilumab 300 mg qw improved proportions of patients achieving co-primary endpoints, ≤6 eos/hpf and absolute change in DSQ score, and secondary endpoints, ≤1 eos/hpf and <15 eos/hpf at Week 24 versus placebo, regardless of history of food elimination diets, PPI use at randomisation, or history of dilation (Table). Improvements were maintained or continued to improve at Week 52. A similar trend was observed for other secondary endpoints assessed. Placebo-treated patients who switched to dupilumab in Part C demonstrated similar efficacy to patients treated with dupilumab in Part B. Dupilumab safety was consistent with the known dupilumab safety profile. Conclusion Dupilumab qw demonstrated sustained improvements in histologic and symptomatic aspects of EoE up to 52 weeks in adults and adolescents with an inadequate response, intolerance, and/or contraindication to STC, regardless of history of food elimination diets, PPI use, or history of oesophageal dilation. Improvements in endoscopic aspects of EoE up to 52 weeks were also observed.

A review of proton pump inhibitor use in cystic fibrosis and considerations for deprescribing.

Use of proton-pump inhibitors (PPIs) is common among people with cystic fibrosis (pwCF) both for the management of suspected GERD, as well as pancreatic enzyme replacement therapy augmentation. Despite their use, limited data exist to demonstrate a clinically significant impact of PPIs on key endpoints in pwCF. Furthermore, the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy may modify the need for use. These notions, coupled with the potential for adverse outcomes associated with long-term PPI use in pwCF, should facilitate re-evaluation of long-term PPI use in pwCF and promote potential deprescribing. Despite limited data on PPI deprescribing in pwCF, it intuitively mirrors the existing guidance in adults in the general population, but with added consideration given to tapering strategy, and monitoring for CF-specific outcomes such as nutritional and respiratory status. The development of a monitoring and re-initiation plan is key to reducing deprescribing inertia. This review aims to summarize the evidence that details the concern for long-term use of PPIs and provide CF clinicians with rationale and guidance on how to approach deprescribing in their practice.

Sex-specific association of chronic proton pump inhibitor use with reduced bone density and quality.

Chronic use of proton pump inhibitors (PPIs) has been associated with an increase in bone fragility. However, evidence on the effect of chronic PPI use on bone density is conflicting, and data on bone microarchitectural quality are scarce. The primary aim of this study was to evaluate whether trabecular bone microarchitecture, assessed by trabecular bone score (TBS), is altered in chronic PPI users. The association between PPI use and bone density was also evaluated as a secondary endpoint. We extracted individual patient data from the 2005-2008 cycles of the population-based National Health and Nutrition Examination Survey (NHANES), in which lumbar spine dual-energy X-ray absorptiometry (DXA) scans were acquired. TBS values were calculated from DXA images using a dedicated software. Multivariable linear regression analyses stratified by sex were performed to evaluate the association of chronic PPI use with TBS and bone mineral density (BMD), adjusting for relevant confounders. A total of 7478 subjects were included (3961 men, 3517 women). After adjustment for relevant confounders, chronic PPI use was associated with a worse bone health profile in men, with lower TBS (-0.039, 95%CI:[-0.058, -0.020], p<0.001), lumbar spine T-score (-0.27, 95%CI:[-0.49, -0.05], p=0.018), total hip T-score (-0.20, 95%CI:[-0.39, -0.01], p=0.038), and femoral neck T-score (-0.21, 95%CI:[-0.42, -0.01], p=0.045). Notably, the association between chronic PPI use and degraded TBS remained statistically significant even after further adjustment for BMD at lumbar spine and femoral neck (-0.026, 95%CI:[-0.039, -0.012], p=0.001). In contrast, no significant association was observed between chronic PPI use and either TBS or BMD in women. Chronic PPI use is associated with degraded trabecular bone quality in men, even after adjustment for BMD. No association was observed in women.

Looking back on a gold standard: a systematic literature review of laparoscopic Nissen fundoplication as an anti-reflux treatment option

Summary Background Laparoscopic Nissen fundoplication is considered the gold standard in surgical management of gastroesophageal reflux disease. Therefore, exhaustive scrutiny of the procedure is necessary. The aim of this study was to perform a complete and systematic literature review of laparoscopic Nissen fundoplication to summarize the evidence for safety and efficacy over time. Methods MEDLINE, Embase, CINAHL, the Cochrane Library, and Web of Science were searched for randomized controlled trials investigating intra- and postoperative outcomes at follow-ups between 4–6 weeks and 17 years. Results Among 1675 screened articles, 63 articles were identified comprising 40 trials with a total of 2619 participants. Intraoperative events included bleeding (2.9%), gastroesophageal injury/perforation (0.9%), and spleen injury/splenectomy (0.9%). One-year clinical follow-up presented the following: dysphagia (22.4%), heartburn or epigastric/sternal pain (15.1%), gas bloating (30.1%), and inability to vomit/belch (16.4%). These outcomes displayed a U-shaped curve with a minimum of symptoms at 1 year. At 10 years postoperatively, clinical outcomes deteriorated, demonstrating dysphagia (45.3%), heartburn or epigastric/sternal pain (30.9%), inability to vomit/belch (48.8%), and gas bloating (44.4%). Furthermore, the surgical benefit seems to dissipate at 17 years. At 1 and 10 years after surgery, reoperation rates were 6.7% and 16.3%, whereas proton pump inhibitor (PPI) use was at 12.3% and 23.3%, respectively. Conclusion The performance of Nissen fundoplication declines over time, as demonstrated by increased PPI medication usage for recurrent symptoms and an increased reoperation rate reaching a combined 39.6%, representing failures after 10 years. The complication rates are dominated by dysphagia, gas bloating, inability to belch/vomit, and/or recurrent reflux symptoms with heartburn.

Does the Use of Gastric-Acid Suppressants Increase the Risk of Peritonitis in Patients Undergoing Peritoneal Dialysis? A Meta-Analysis.

Gastric-acid suppressants (GASs) are commonly prescribed to patients undergoing peritoneal dialysis for various gastrointestinal disorders. However, long-term GAS use has been linked with the risk of enteric peritonitis in this patient population. To assess the association between the enteric peritonitis risk and GAS use in patients undergoing peritoneal dialysis for end-stage renal disease, we conducted a systematic search for relevant articles published until December 2023 in PubMed, Embase, and the Cochrane Library databases. We included 11 articles on the association between GAS use and enteric peritonitis risk in patients undergoing peritoneal dialysis. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) using fixed and random-effects models to obtain overall effect estimates. We also explored potential sources of heterogeneity through subgroup analyses. We qualitatively analyzed data from 11 studies (n = 1993 participants), out of which, nine studies were included in meta-analysis. The overall results revealed a significant association between the enteric peritonitis risk and the use of GASs (OR, 1.61; 95% CI, 1.26-2.05; p < 0.00001). The analysis of study design subgroups showed a significant association in retrospective cohort studies (OR, 1.70; 95% CI, 1.42-2.03; p < 0.00001) but not in case-control studies. Histamine-2 receptor antagonist (H2RA) use was significantly associated with enteric peritonitis (OR, 1.49; 95% CI, 1.05-2.11, p = 0.03), whereas proton pump inhibitor use was not (OR, 1.13; 95% CI, 0.72-1.77, p = 0.28). Our findings suggest a significant association between the development of enteric peritonitis and GAS use in patients undergoing peritoneal dialysis. However, the observed heterogeneity in study characteristics warrants caution in interpreting the results.

Shifts in Serum Bile Acid Profiles Associated With Barrett's Esophagus and Stages of Progression to Esophageal Adenocarcinoma.

Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression. Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression. A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11-3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04-3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes. Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.

Effect of metabolic dysfunction-associated steatotic liver disease on BNT162b2 immunogenicity against the severe acute respiratory syndrome coronavirus 2 omicron variant.

We aimed to investigate the effect of metabolic dysfunction-associated steatotic liver disease (MASLD) on three-dose BNT162b2 immunogenicity to the omicron variant. Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer≥10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter≥248dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID-19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use. One hundred forty-eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0years [interquartile range, IQR: 44.5-57.3]) were recruited. The median time from the first dose to the third dose was 8.5months (IQR: 7.9-8.9). MASLD subjects had a lower seroconversion rate than non-MASLD ones (89.6% vs 99.0%; P=0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002-0.440). Subgroup analysis of immunogenicity at 4months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69-22.20] vs 33.49 [IQR: 24.05-46.53]; P=0.004) and seroconversion rate (76.9% vs 97.4%; P=0.016) in MASLD than non-MASLD subjects, but not within 4months from the third dose (vMN titer: 46.87 [IQR: 33.12-66.02] vs 41.86 [IQR: 34.47-50.91], P=0.240; seroconversion rate: 94.3% vs 100%, P=0.131). Metabolic dysfunction-associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three-dose BNT162b2 recipients.

Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation

BackgroundConcomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results.MethodsFrom a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3–5) and gastrointestinal (GI) bleeding (BARC types 3–5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis.ResultsOf 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18–8.78). The incidence of major bleeding and GI bleeding (BARC types 3–5) was comparable between PPI users and non-users in the PS-matched cohort.ConclusionsIn post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Association Between Proton Pump Inhibitors and the Risk of Intestinal Behçet Disease.

This study aimed to investigate the association between proton pump inhibitor (PPI) use and the incidence of intestinal Behçet disease (BD) in patients with BD. A retrospective cohort study was conducted at The University of Tokyo Hospital, including patients with BD diagnosed between April 2005 and November 2023. Cox models and Kaplan-Meier analyses were used to evaluate hazard ratios (HRs) and cumulative incidence of intestinal BD, respectively. Secondary analyses were performed to assess the duration and dose-response relationship of PPI use. Among 194 patients with BD, 25.3% developed intestinal BD during a mean follow-up of 12 years. PPI users had a significantly higher incidence of intestinal BD compared to nonusers (adjusted HR 2.48, 95% CI 1.38-4.47, P = 0.002), with a confirmed duration/dose-dependent relationship. The cumulative incidence of intestinal BD was markedly elevated in PPI users (log-rank P < 0.001). The result was similar to that in the propensity score-matched cohort. This study demonstrates a significant association between PPI use and increased incidence of intestinal BD in patients with BD. Caution in prescribing PPIs for patients with BD is warranted due to the potential risk of severe complications associated with intestinal BD.

Association between proton pump inhibitors use and the severity of periodontal disease and peri-implantitis: a systematic review.

This systematic review investigates the probable effect of proton pump inhibitor (PPI) use on the severity of periodontal disease and peri-implantitis and implant survival. We conducted a literature search in PubMed, Scopus, and Cochrane Central Library up to April 2024. Two review authors independently screened the title and abstracts and then the full texts of retrieved studies. Observational and clinical trial studies that assessed the association between PPIs use and periodontal disease severity and peri-implantitis or implant survival were included. Data extraction from the included studies was done by two reviews independently. Of 940 studies initially retrieved from online searching, 7 research met the inclusion criteria. Three studies examined periodontitis, while four focused on peri-implantitis and implant longevity. On the contrary, evidence regarding the impact of PPIs use on peri-implantits and implant survival is conflicting. Therefore, more well-designed RCTs are warranted to come to a definite conclusion. Since proton pump inhibitors alter the gut microbiome, and affect bone, plus the pathogenesis and etiology of periodontal disease are affected by bacteria within the periodontal pocket, it is hypothesized that they may affect periodontal pathogenesis.

Association between preoperative proton pump inhibitor use and postoperative acute kidney injury in patients undergoing major surgery

Background Acute kidney injury (AKI) is a severe postoperative complication in patients undergoing major surgery. Proton pump inhibitors (PPIs) are used preoperatively as prophylaxis for postoperative gastrointestinal bleeding. Whether preoperative PPI use is associated with an increased risk of postoperative AKI remains uncertain. Methods This retrospective cohort study used electronic medical records from the clinical data warehouse of Peking University First Hospital to screen all adult hospitalizations undergoing major surgery between 1 January 2018 and 31 December 2020. Exposure was preoperative PPI use, defined as PPI use within 7 days before major surgery. The primary outcome was postoperative AKI, defined as AKI occurring within 7 days after major surgery; secondary outcomes included in-hospital AKI and in-hospital mortality. Results A total of 21,533 patients were included in the study (mean [SD] age, 57.8 [15.0] years; 51.2% male), of which 944 (4.4%) were prescribed PPI within 7 days before major surgery (PPI users). Overall, 72 PPI users (7.6%) and 356 non-users (1.7%) developed postoperative AKI. After adjustment, preoperative PPI use was associated with an increased risk of postoperative AKI (adjusted OR, 1.47; 95% CI, 1.04–2.07) and in-hospital AKI (adjusted OR, 1.41; 95% CI, 1.03–1.94). Moreover, subgroup analyses showed that the risk of PPI on postoperative AKI was amplified by the concomitant use of non-steroidal anti-inflammatory drugs or diuretics. No significant difference was observed between preoperative PPI use and in-hospital mortality in the fully adjusted model (adjusted OR 1.63; 95% CI, 0.55–4.85). Conclusions Preoperative PPI use was associated with an increased risk of AKI in patients undergoing major surgery. This risk may be enhanced by the concomitant use of other nephrotoxic drugs. Clinicians should weigh the pros and cons before initiating PPI prophylaxis.

Effect of concomitant use of esomeprazole on levodopa pharmacokinetics and clinical symptoms in patients with Parkinson's disease

BackgroundProton pump inhibitors (PPIs), which inhibit gastric acid secretion, are frequently prescribed to patients with Parkinson's disease (PD). Levodopa, the gold-standard treatment for PD, demonstrates enhanced solubility in acidic environments. Although PPIs increase gastric pH and may affect levodopa absorption, the effect of concomitant PPI use on levodopa pharmacokinetics in patients with PD remains unknown. This study aimed to investigate the effect of the concomitant use of esomeprazole, a PPI, on the pharmacokinetics of levodopa and carbidopa and clinical symptoms in patients with PD. MethodsWe prospectively enrolled 40 patients with PD and compared the pharmacokinetics of levodopa and carbidopa and clinical symptoms before and two weeks after the concomitant use of esomeprazole. ResultsThe plasma concentrations of levodopa 30 min after concomitant oral administration of levodopa and esomeprazole were significantly lower (4.92 ± 4.10 μmol/L) than those without concomitant esomeprazole use (6.26 ± 3.75 μmol/L; p = 0.027). The plasma concentrations of carbidopa showed no significant differences with respect to concomitant esomeprazole use. Significant elevation was recorded in all subscores of the Movement Disorder Society-sponsored revision of the Unified Parkinson's disease Rating Scale scores after concomitant use of esomeprazole. No significant differences were observed between Helicobacter pylori-negative and Helicobacter pylori-positive patients. Non-elderly patients (age ≤ 70 years) tended to be more susceptible to the effect of esomeprazole on levodopa pharmacokinetics and clinical symptoms. ConclusionsThe unnecessary use of PPIs should be avoided in patients with PD, especially in non-elderly patients, to improve absorption of levodopa.

Proton pump inhibitor use and bone fractures in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at high risk for bone fractures, which are associated with high morbidity and mortality. Proton pump inhibitors (PPI) have been linked to an increased risk for fractures in the general population as well as in patients with need for hemodialysis, but studies in patients with CKD are currently missing. We performed a population-based observational case-control study exploring a sample of patients with CKD derived from the IQVIATM Disease Analyzer database. Patients with and without fractures were matched using the 1:1 nearest neighbor propensity score matching method. To investigate the association between PPI use and fractures, multivariable logistic regression analyses were performed adjusting for confounding factors. In total, 6076 patients with and 6076 patients without fractures were matched and subsequently available for analyses. In the total cohort, PPI use was associated with an increased risk for fractures (OR 1.68; 95% CI 1.55-1.83). This association was noted for nearly all types of fractures. The strongest association between PPI use and fractures was found in patients below the age of 60 with a PPI prescription for longer than two years (OR 6.85, 95% CI 1.85-25.38). The same was true, when analyzing cumulative PPI doses. Here, patients below the age of 60 with a cumulative PPI dose above 16000mg (highest quartile) had the highest risk for fractures (OR 4.62, 95% CI 1.87-11.44). There was no difference between men or women regarding the association between PPI use and fractures. This study provides evidence that PPI use is associated with fractures in patients with CKD. Deprescription of PPI in patients without an indication for treatment could be a modifiable risk factor to reduce fracture risk in this high-risk group.

O-200 Association between proton pump inhibitors use and the risk of maternal infections during pregnancy and postpartum: a Swedish population-based cohort study

Abstract Study question Is there an association between use of proton pump inhibitors (PPIs) and maternal infection during or after pregnancy and subsequent pregnancy complications? Summary answer Use of PPIs in the 3 months before pregnancy or during the first trimester was associated with an elevated risk of maternal infection. What is known already PPIs alter gastric acidity and the gut microbiome, which may increase infection risks in the general population, but their impact on pregnant women is unknown. Study design, size, duration We conducted a Nationwide population-based cohort study using data from Swedish healthcare registers. PPIs use was defined as ≥ 1 prescription fill of a PPI in the 90 days before the first day of the last menstrual period (LMP) to the end of the 1st trimester (LMP+97 days). Maternal infections were identified from the start of the 2nd trimester to 90 days postpartum and classified as mild, moderate/ severe infections, and infection-related pregnancy complications. Participants/materials, setting, methods All pregnancies resulting in live or stillbirths between 2006 to 2019 in Sweden, identified using the Medical Birth Register. Log-binomial regression was used to estimate associations (relative risk (RR) and 95% confidence intervals (CI)) between PPIs and maternal infection, adjusting for potential confounders including birth year, maternal age at delivery, early pregnancy BMI, comorbidities, smoking in early pregnancy, maternal country of birth, maternal education, and parity. Main results and the role of chance Among 1,510,560 pregnant women, 42,599 (2.8%) used PPIs, and use increased over the study period time from 1.5% in 2006 to 3.44% in 2019. Compared to pregnant women without PPI use, those with PPI use had higher rates and risks of any infection (49.7% vs 36.8%; adjusted RR 1.30, 95%CI 1.29-1.32), mild infection (20.9% vs 16.1%; adjusted RR 1.30, 95%CI 1.28-1.33), moderate to severe infection (23.4% vs 15%; adjusted RR 1.47, 95%CI 1.45-1.50), and infection-related pregnancy complications (11.2% vs 9.2; adjusted RR 1.12, 95%CI 1.09-1.15). Conclusion Our results show an association between PPI use and an elevated risk of infection in pregnant women. Next steps include the further investigation into the infection types. PPI therapy has benefits and drawbacks that should be carefully weighed, especially in patients who are prone to infections. While our study highlights potential concerns, it does not imply that all pregnant women are at increased risk. More research is needed to understand the underlying mechanisms and assess potential preventive measures. Prescribing PPIs during pregnancy should be determined on a case-by-case basis, considering the patient’s individual health state. We acknowledge the necessity for caution, particularly in vulnerable populations, and more research is needed to demonstrate clinical correlations. Limitations, reasons for caution Potential confounding by indication due to underlying morbidities cannot be fully accounted for. Further research is required to establish clinical connections. Wider implications of the findings Clinicians should carefully weigh the benefits of PPI therapy during pregnancy, particularly in patients prone to infections. Trial registration number not applicable

Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study

ObjectivesWe aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.DesignRetrospective cohort study.SettingThis research was conducted at...

Proton Pump Inhibitors and Risk of COVID-19 Infection in Children

To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children. This retrospective, case-control study included all children ≤21years undergoing COVID-19 polymerase chain reaction testing at a tertiary children's hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes. 116 209 patients age 8.5±6.2years underwent 234 867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI nonuse [RR 0.85 (95% CI 0.76, 0.94), P=.002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P=.77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P=.26]. We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children.

Association between Proton Pump Inhibitor Use and Risk of Incident Chronic Kidney Disease: Systematic Review and Meta-Analysis.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis. We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs). Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16-1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13-1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes. Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.

Effect of proton pump inhibitors versus histamine-2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers.

To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.

Natural language processing assisted detection of inappropriate proton pump inhibitor use in adult hospitalised patients

ObjectivesTo establish a clinical application monitoring system for proton pump inhibitors (PPI-MS) and to enhance the detection and intervention of inappropriate PPI use in adult hospitalised patients.MethodsNatural language processing technology...

Impact of pharmacist-evaluated clinical decision support system alerts on potentially missing or inappropriately prescribed proton pump inhibitors at hospital discharge: a retrospective cross-sectional study

BackgroundProton pump inhibitors (PPIs) are among the most prescribed drugs. A clinical decision support system (CDSS) could improve their rational use.AimThe impact of an electronic algorithm (e-algorithm) implemented in a CDSS on potentially missing or inappropriately prescribed PPIs at hospital discharge, its specificity and sensitivity, and the outcome of the alerts issued were analysed.MethodAn e-algorithm continuously monitored patients of a tertiary care hospital for missing or inappropriate PPIs. Following relevance assessment by a pharmacist, the alerts raised were either displayed in the patients’ electronic record or dismissed. After a three-month period, all adult patients’ records were retrospectively reviewed for missing or inappropriate PPIs at discharge. The results were compared with a corresponding period before CDSS introduction. Sensitivity, specificity and outcome of alerts were quantified.ResultsIn a 3-month period with 5018 patients, the CDSS created 158 alerts for missing PPIs and 464 alerts for inappropriate PPIs. PPI prescribing was proposed 81 times and PPI termination 122 times, with acceptance rates of 73% and 34%, respectively. A specificity of 99.4% and sensitivity of 92.0% for missing PPIs and a specificity of 97.1% and a sensitivity of 69.7% for inappropriate PPIs were calculated. The algorithm reduced incidents of missing PPIs by 63.4% (p < 0.001) and of inappropriate PPIs by 16.2% (p = 0.022).ConclusionThe algorithm identified patients without necessary gastroprotection or inappropriate PPIs with high specificity and acceptable sensitivity. It positively impacted the rational use of PPIs by reducing incidents of missing and inappropriate PPIs.