Duration Of Proton Pump Inhibitors Therapy Research Articles

Long-Term Intake of Proton-Pump Inhibitors Could Be Associated with an Increased Incidence of Liver Cancer in Women.

Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06-1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09-1.55) did it reach the predefined level of significance (p < 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09-1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21-3.26). Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication.

The impact of pharmacist intervention on the intravenous-to-oral switch therapy of proton pump inhibitors in cardiovascular surgery

ABSTRACT Background The prescriptions of proton pump inhibitors (PPIs) have been widely concerned due to both huge increase in medical costs and possible long-term adverse events (AEs) caused by the improper route of drug administration. The aim of this study was to assess the effectiveness of pharmacist interventions on the clinical outcome and safety of switching from intravenous (IV) to oral PPIs therapy. Patients and methods A retrospective, single-center, pre- intervention (early -stage)- and intervention (later -stage) study was performed in a Chinese hospital. Results A total of 1736 patients were included in the study. After 12 months of interventions, significant improvements in the number of rational IV to oral switch in patients with oral switch indications were found. The median duration of oral therapy was increased, while the duration of PPIs therapy was decreased. Pharmacist interventions led to significant reductions in mean PPI costs, mean total drug costs, mean hospitalization costs, and the risk for long-term adverse events. Conclusion This study provides important evidence on the beneficial effect of pharmacist interventions on promoting an optimal IV to oral switch of PPIs and substantial cost saving by shortening the duration of IV PPIs therapy and reducing the risk for long-term AEs.

Prescribing Patterns of Proton Pump Inhibitors in Germany: A Retrospective Study Including 472 146 Patients.

The aims of this study were to analyze proton pump inhibitor (PPI) users in Germany, defining and classifying them in terms of treatment appropriateness, and to analyze the PPI prescription practices of healthcare providers. The updated DGVS (Deutsche Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten) gastroesophageal reflux disease (GERD) treatment guideline (published March 2023) for mild heartburn symptoms recommends carrying out a probatory treatment of mild symptoms via other medication such as antacids, alginates, and H2 blockers before escalating to PPI treatments, if the patient profile allows. This retrospective cross-sectional study was based on data from the IQVIA™ Disease Analyzer database (DA) and included adult patients (18 years or older) in 1006 general and 39 gastroenterological practices in Germany who received at least 1 PPI prescription or alginate between September 2019 and September 2021 (hereinafter referred to as the index period). Analyses included indications associated with PPI prescription, co-diagnoses, co-therapies of PPI patients, duration of PPI therapy, dosages of PPI prescriptions, and proportions of practices prescribing PPIs and alginates. A total of 472 146 patients taking PPIs and 9101 patients taking alginates were available for analysis. Very few patients (4.5%) of the total cohort were treated in complete adherence to treatment guidelines. Conditions such as gastritis and duodenitis (47.2%) and reflux diseases (38.4%) were more frequently associated with PPI prescriptions. The average PPI treatment period lasted 141 days, and 36.6% of patients were treated for >6 months. High doses were prescribed relatively often (ie, 42.8% of esomeprazole prescriptions were 40 mg, 59.1% of lansoprazole prescriptions 30 mg, 28.6% of omeprazole prescriptions 40 mg). With each practice prescribing PPIs to at least 10% of their patients; 72% of general practitioners (GPs) and 8% of GENTS (Gastroenterologists) prescribed alginates. This study highlights that discrepancies exist between clinical guidelines and real-life prescribing practices of PPIs in Germany. Particular attention should be given to the incidence of patients being prescribed high-dose or long-duration PPI with mild indications. These findings are particularly apt considering the publication (March 2023) of new guidelines on the "management of gastroesophageal reflux disease and eosinophilic esophagitis," by the DGVS.

Annals for Educators - June 2021.

Annals for Educators - June 2021.

Opportunities for successful de-escalation of proton pump inhibitors at a federally qualified health center

BackgroundA Proton Pump Inhibitor (PPI) de-escalation initiative was piloted at a Family Medicine Federally Qualified Health Center (FQHC) after a needs assessment showed that PPIs were prescribed inappropriately. The objective was to evaluate implementation of a PPI de-escalation program for an urban, underinsured patient population at a (FQHC).MethodsPatients receiving PPI with an upcoming appointment with their primary care provider (PCP) were evaluated by a pharmacist for the appropriateness of therapy. The pharmacist administered a questionnaire to patients to assess PPI usage patterns and then evaluated for appropriate PPI therapy which included diagnoses, risk factors for gastrointestinal bleed, symptom control, and duration of PPI therapy. For consenting patients, de-escalation was implemented per pharmacist protocol.ResultsA total of 36 patients were evaluated for appropriate PPI use, among those, 21 (58%) were eligible for de-escalation, and 19 agreed to de-escalation. Fifteen patients (15/19) had successful PPI de-escalation after 4 weeks without discomfort or symptoms which disrupted daily activities.ConclusionsThis pharmacist led initiative in collaboration with PCPs resulted in successful de-escalation of PPIs in an underserved primary care setting.

The Use and Misuse of Proton Pump Inhibitors: An Opportunity for Deprescribing

Proton pump inhibitors (PPIs) are proven medications of choice for gastroesophageal reflux disease (GERD), acid-related disorders, erosive esophagitis, Barrett esophagus, prevention of gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs, eosinophilic esophagitis, peptic ulcer disease, stress ulcer prophylaxis in critically ill patients, and other indications. Best practice guidelines from several sources on the appropriate indications and duration of PPI therapy have been summarized for easy assimilation. Individualized decision with regard to PPI use is illustrated by case vignettes; best approaches are provided.The significant increase in use of PPIs for ill-defined indications over the years, associated adverse outcomes with long-term use, and consequent increase in health care costs have drawn much attention. Adverse outcomes due to PPI therapy may be categorized as unrelated or related to gastric acid inhibition. Examples of outcomes unrelated to acid inhibition include allergic reactions, acute interstitial nephritis, chronic kidney disease, poor cardiovascular outcomes, dementia, and drug interactions; consequences of acid inhibition include gastrointestinal infections, pneumonia, nutrient deficiencies, fractures, spontaneous bacterial peritonitis, and small intestinal bacterial overgrowth.Provider awareness regarding best practice guidelines on PPI use and imparting pertinent education to patients may be the rational approach to safe and effective PPI therapy. In individuals in whom the drug is not indicated, efforts at deprescribing the PPI may be attempted following discussion with the patient. Approaches include stopping the drug, reducing the dose or using “on-demand” therapy after completing the course of treatment for the specific indication. Barriers to successful deprescribing exist. Follow-up is recommended for recurrence of manifestations; in the event of recurrence, the PPI may need to be re-instituted.PPIs are valuable, irreplaceable drugs in the prevention and treatment of certain disorders for specific durations of time. Evidence nevertheless suggests that excessive and inappropriately prolonged use of PPIs is associated with a broad range of adverse effects. Education of provider and patient, stewardship, and motivation are key to appropriate use of PPIs for the right indications. Key implications for practice are offered.

Use of Proton Pump Inhibitors in Hungary: Mixed-Method Study to Reveal Scale and Characteristics.

BackgroundDue to their efficacy and tolerability, utilization of proton pump inhibitors (PPI) has significantly increased worldwide. Parallel to the clinical benefits, potential long-term side effects have been observed, which, along with increasing medical expenses and potential drug interactions, justifies the analysis of the trends of utilization.ObjectiveThe aim of the present study was to show the level, pattern, and characteristics of PPI use.MethodsWe assessed the nationwide use of proton pump inhibitors in ambulatory care based on aggregated utilization data from the National Health Insurance database. The annual PPI utilization was expressed as the number of packages and as number of DDDs per 1,000 inhabitants and per year. For 2018, we estimated PPI exposure as the number of packages and as the number of DDDs per user per year. The annual reimbursement costs of proton pump inhibitors were also calculated. Moreover, three patient-level surveys were carried out in non-gastroenterological inpatient hospital departments to reveal characteristics of proton pump inhibitor use, namely dose, duration, and indication.ResultsThe PPI utilisation increased from 5867.8 thousand to 7124.9 thousand packages and from 41.9 to 50.4 DDD per 1,000 inhabitants and per day between 2014 and 2018. Nationwide data showed that 14% of the adult population was exposed to proton pump inhibitors in 2018, while among hospitalized patients, the prevalence of proton pump inhibitor use was between 44.5% and 54.1%. Pantoprazole was the most frequently used active ingredient, both in the nationwide data and in the patient-level surveys. In the patient-level survey in majority of patients (71.5%–80.0%) proton pump inhibitors were prescribed for prophylaxis. Many inpatients (29.4%–36.9%) used 80 mg pantoprazole per day. The average number of PPI packages per user was 6.5 in 2018 in the nationwide data. The duration of PPI therapy was typically between 1 and 5 years in the patient-level surveys and nearly 20% of the inpatients had been taking proton pump inhibitors for more than 5 years.ConclusionsOur data suggests that Hungarian patients receive proton pump inhibitors in high doses and for a long time. Use of proton pump inhibitors beyond their recommended indications was also found.

Proton pump inhibitors in patients with liver cirrhosis - a survey among hepatologists in Germany

Proton pump inhibitors (PPI) are one of the most frequently prescribed drugs worldwide. In particular, in patients with liver cirrhosis prescription rates up to 78 % have been reported. PPI may be a risk factor for nosocomial infections, spontaneous bacterial peritonitis and onset of hepatic encephalopathy. Aim of this survey was to assess the prescription practice of PPI in patients with cirrhosis in Germany. We performed a web-based survey among hepatologists and gastroenterologists. The invitations for the survey have been sent out via the newsletter of German gastroenterological societies (DGVS, BVGD and AUG). 61 persons have participated in the survey. Overall, high PPI prescription rates have been reported (58 % in inpatient and 44 % in outpatient setting). Almost half of the respondents reported that PPI are frequently prescribed without clear indication (such as abdominal discomfort). One third reported that the PPI therapy could be stopped after critical evaluation of the indication. 55 % of the respondents stated that according to their estimates PPI are associated with adverse reactions. Bleeding was only very rarely seen after termination of PPI treatment. PPI are frequently prescribed among patients with liver cirrhosis in Germany. Prescribers are aware of an unclear risk-benefit ratio. Further prospective data are urgently needed to increase evidence regarding indication and duration of PPI therapy in patients with cirrhosis.

Proton-pump inhibitors: understanding the complications and risks.

Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.

The use of proton pump inhibitors is positively associated with osteoporosis in postmenopausal women in Germany

Objectives: To analyze the association between the use of proton pump inhibitors (PPIs) and osteoporosis in German postmenopausal women.Methods: This study included 3092 women with osteoporosis and 3092 women without osteoporosis. Cases and controls were matched on the basis of age, health insurance, index year, and physician. The main outcome of the study was the risk of osteoporosis dependent on predefined risk factors. Gastrointestinal disorders potentially associated with osteoporosis were determined. The presence of PPIs including the duration of therapy was also assessed. Multivariate logistic regression models were fitted with osteoporosis as a dependent variable.Results: The mean age was 72.3 years; 5.6% of both osteoporosis patients and controls had private health insurance coverage. Gastrointestinal disorders occurred significantly more frequently in osteoporosis patients than in controls. The use of PPI drugs was also significantly more common in osteoporosis patients than in matched controls. Osteoporosis development was found to be associated with disorders of the esophagus (odds ratio (OR) 1.19, p = 0.013) and gastritis/duodenitis (OR 1.14; p = 0.045). Interestingly, the use of PPIs also led to an increase in the risk of developing osteoporosis (OR 1.62; p < 0.001). Finally, the odds of being diagnosed with osteoporosis increased with the duration of PPI therapy from 1.58 for 1 year of therapy or less to 1.72 for at least 5 years of treatment.Conclusions: The use of PPIs was a risk factor for osteoporosis and this risk increased with therapy duration in German women. Esophagus disorders and gastritis/duodenitis also increased the risk of developing this chronic condition.

Impact of a Multifaceted Intervention on Prescribing of Proton Pump Inhibitors for Stress Ulcer Prophylaxis in the Critically Ill

Background:: Lack of well-supported evidence clearly defining one agent as superior to the other for use in stress ulcer prophylaxis (SUP) has led to an array of treatment strategies. Studies comparing histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) have shown H2RAs to be non-inferior to PPIs at preventing clinically significant gastric bleeding. This, in addition to the decreased cost associated with H2RAs, has led to the adoption of H2RAs as the preferred agent for SUP at our institution. Objectives:: To evaluate the impact of developing a guideline and removing PPIs from computerized order entry PowerPlans on PPI prescribing for SUP in critically ill patients. Patients and Methods:: Members of the critical care service developed a guideline to direct SUP and removed pantoprazole from two critical care admission PowerPlans. In this interventional study with a historical control, adult patients admitted to the medical or surgical-trauma ICU and prescribed a PPI were evaluated during two time periods before and after the interventions. Patients were excluded if they were receiving a PPI for a reason other than SUP. Patients were assessed daily for an indication for SUP. These included mechanical ventilation, high dose steroids, and coagulopathy. Results:: A total of 92 and 60 patients were included in the pre- and post-intervention groups, respectively. PPI use for SUP was reduced from 38% in the pre-intervention group to 15.6% in the post-intervention group (P < 0.0001). PPI days adjusted for LOS were not different between the pre- and post-intervention groups (84% vs 86%, P = 0.5909). Of the total PPI days, 52.4% (95% CI 48.8 - 56.1) were classified as inappropriate because there was no indication, while the remaining 47.6% (95% CI 43.9 - 51.2) had an indication but should have received a H2RA. The total cost associated with guideline non-adherence was $1802. Conclusions:: Our multifaceted intervention reduced the number of days in which a PPI was prescribed for SUP in the overall ICU population; however, it did not impact the duration of PPI therapy. Patients either had no indication for SUP, or had an indication where less costly H2RAs could have been used. Additional opportunity exists to improve cost-effective prescribing of SUP for critically ill patients.

Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Current Role and Future Perspectives

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized by symptoms related to esophageal dysfunction, eosinophil-predominant inflammation, and lack of response to high-dose proton pump inhibitor (PPI) therapy. Responsiveness to PPI therapy in patients with suspected EoE has been historically assumed as evidence of gastroesophageal reflux disease (GERD), but this concept has rapidly changed over the past few years. A novel phenotype, termed PPI-responsive esophageal eosinophilia (PPI-REE), was described in 2011. PPI-REE refers to patients who appear to have EoE, but who achieve complete remission after PPI therapy. Currently, a PPI trial is mandatory before diagnosing EoE since 30–40 % of EoE patients will be eventually diagnosed with PPI-REE. Evolving evidence on PPI-REE suggests it is not simply GERD but actually a subphenotype of EoE, given the fact PPI-REE and EoE remain genetically and phenotypically indistinguishable. Instead of PPI-REE, the term PPI-responsive EoE might be more accurate to name this entity. PPI-REE might occur with either normal or pathological esophageal pH monitoring. PPI therapy can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Whether esophageal barrier impairment is the cause of the effect of esophageal eosinophilia and whether PPI therapy primarily targets barrier or inflammation healing in PPI-REE have not been yet elucidated. The natural history of the disease, long-term doses, and duration of PPI therapy, as well as factors influencing symptom and/or inflammation relapse remain yet unknown. The mechanism as to why among identical patients, some respond to PPI therapy (PPI-REE) while others do not (EoE), warrants further research.

Clinical Improvement of Severe Reflux Esophagitis in Korea: Follow-up Observation by Endoscopy

Background/Aims: The natural history of severe erosive reflux disease in Korea remains uncertain. We aimed to evaluate endoscopic follow-up results in subjects with severe reflux esophagitis under routine clinical care. Materials and Methods: A total 61,891 subjects underwent an upper endoscopic examination in the health check-up program from January 2007 to December 2013. We reviewed medical charts of patients who had been diagnosed with severe reflux esophagitis. The severity of reflux esophagitis was determined by the Los Angeles (LA) classification system. Patients underwent at least one follow up endoscopy after diagnosis of severe reflux esophagitis. We classified the patients into two groups; regressed in severity and remained unchanged, according to follow up endoscopic status. Results: Based on endoscopic findings, 5,938 subjects (9.6%) were found to have reflux esopohagitis: 121 subjects (0.2%) in LA-C; 39 subjects (0.06%) in LA-D. Among 31 patients who had endoscopic follow-up, 23 patients (74.2%) showed regression from LA C/D to LA A/B or minimal change disease or normal. The mean follow up duration was 42.2 months in regression group and 53.2 months in no change group. All patients had been treated with proton pump inhibitors (PPIs) on a regular or on-demand basis. Age, sex, smoking, alcohol, exercise, hypertension, diabetes mellitus, dyslipidemia, sliding hiatal hernia, body mass index, waist circumference and duration of PPIs therapy did not significantly influence regression of severe reflux esophagitis. Conclusions: The majority of severe reflux esophagitis patients under routine clinical care showed improvement on endoscopic follow-up. (Korean J Helicobacter Up Gastrointest Res 2015;15:231-235)

Monitoring of Vitamin D in Chronic PPI Users Is Influenced by Patient Age and Duration of Therapy

Purpose: Proton pump inhibitors (PPIs) are commonly prescribed medications. Chronic use of PPIs has been associated with bone fractures. The risk is enhanced with increased patient age and longer duration of therapy. Monitoring and supplementing vitamin D levels may reduce fracture risk. This study evaluated the rate of vitamin D measurement based upon patient age and the duration of PPI therapy. Methods: A retrospective medical record review was performed utilizing a multispecialty electronic health record. Consecutive patients on chronic PPIs during a 6-month period seen in an urban, academic gastroenterology clinic were included. There were no exclusion criteria. Patient age, gender, PPI dose and duration, and vitamin D level were obtained. A database, maintaining patient confidentiality, was created. Statistical analysis was performed using Fisher's exact test with two-tailed p-values and 95% confidence intervals (CIs) computed for continuous variables. Statistical significance set at p<0.05. This study was approved by the university's IRB. Results: Two hundred thirty-four records (88 men, 146 women; mean age 54.9 years) were reviewed. One hundred sixteen (49.6%) had vitamin D levels checked. There was no significant difference (p=0.345) in vitamin D measurement based upon gender. The mean age of patients with vitamin D measured was 60.6 years (95% CI 58.2-63.1) and 49.2 years (95% CI 48.6-51.7) in those with vitamin D not measured (p=1.16x10-9). There was a significant difference (p<0.0001) in the rate at which vitamin D was checked in patients 60 years and older (65 of 90; 68.4%) compared to patients younger than 60 years (51 of 139; 36.7%). There was a significant difference (p<0.0001) in the rate of vitamin D measurement in patients treated 24 months and longer (56 of 80; 70%) compared to those treated less than 24 months (60 of 154; 39%). Conclusion: Chronic use of PPIs has been associated with increased fracture risk. The risk is increased with longer duration of therapy and increased patient age. Supplementation of low vitamin D levels may mitigate the risk of fractures. This study revealed that there was inconsistent measurement of vitamin D, with only half of chronic PPI users having a vitamin D level documented in their medical record. Patients on PPIs 24 months or longer and patients who were 60 years and older had vitamin D measured more frequently. These results suggest that physicians recognize the factors that increase fracture risk in patients maintained on PPIs. However, increased efforts are needed to encourage monitoring of vitamin D levels in all patients on chronic PPI therapy.

Clinical usefulness of adherence to gastro-esophageal reflux disease guideline by Spanish gastroenterologists

To investigate usefulness of adherence to gastro-esophageal reflux disease (GERD) guideline established by the Spanish Association of Gastroenterology. Prospective, observational and multicentre study of 301 patients with typical symptoms of GERD who should be managed in accordance with guidelines and were attended by gastroenterologists in daily practice. Patients (aged > 18 years) were eligible for inclusion if they had typical symptoms of GERD (heartburn and/or acid regurgitation) as the major complaint in the presence or absence of accompanying atypical symptoms, such as dyspeptic symptoms and/or supraesophageal symptoms. Diagnostic and therapeutic decisions should be made based on specific recommendations of the Spanish clinical practice guideline for GERD which is a widely disseminated and well known instrument among Spanish in digestive disease specialists. Endoscopy was indicated in 123 (41%) patients: 50 with alarm symptoms, 32 with age > 50 years without alarm symptom. Seventy-two patients (58.5%) had esophagitis (grade A, 23, grade B, 28, grade C, 18, grade D, 3). In the presence of alarm symptoms, endoscopy was indicated consistently with recommendations in 98% of cases. However, in the absence of alarm symptoms, endoscopy was indicated in 33% of patients > 50 years (not recommended by the guideline). Adherence for proton pump inhibitors (PPIs) therapy was 80%, but doses prescribed were lower (half) in 5% of cases and higher (double) in 15%. Adherence regarding duration of PPI therapy was 69%; duration was shorter than recommended in 1% (4 wk in esophagitis grades C-D) or longer in 30% (8 wk in esophagitis grades A-B or in patients without endoscopy). Treatment response was higher when PPI doses were consistent with guidelines, although differences were not significant (95% vs 85%). GERD guideline compliance was quite good although endoscopy was over indicated in patients > 50 years without alarm symptoms; PPIs were prescribed at higher doses and longer duration.

M1886 Proton Pump Inhibitor Related Acute Interstitial Nephritis

INTRODUCTION: An increasing number of case reports have identified acute kidney injury (AKI) secondary to acute interstitial nephritis (AIN) provoked by Proton Pump Inhibitor (PPI) therapy. The present collaborative study identifies experience from a major UK renal unit. AIMS & METHODS: All cases of biopsy-proven AIN between Jan 1st 2007 and October 1st 2008 presenting to the regional renal centre (serving a population of 1.1 million), were identified. The notes of all patients (pts) with a diagnosis of AIN and a history of PPI were analysed. Pre-PPI treatment, diagnosis and most recent plasma creatinine and estimated glomerular filtration rate (eGFR) were obtained. Pts were deemed likely to have PPI-associated AKI if a deterioration in kidney function was identified after starting PPI therapy in the absence of a history of any other medications associated with AIN and other renal or systemic causes. RESULTS: 210 kidney biopsy reports were analysed of which 27 reported AIN due to a multitude of causes. Of these, 6 cases of AIN were found to be strongly associated with PPI therapy. PPI's were the most common drug class associated with AIN. Male : Female 1 : 5. The median age at diagnosis was 66 yrs (range 60-86). All pts presented with nonspecific malaise and tiredness. 5 cases were due to omeprazole & 1 pt esomeprazole. Mean ± SD duration of PPI therapy was 7.7 ± 5.6 months, (range 5-18). Mean ± SD pre-PPI creatinine was 73 ± 30 μmol/L (range 45-103); eGFR 69 ± 23 ml/min/1.73m2 (range 4590). At diagnosis, mean ± SD creatinine was 269 ± 217 μmol/L (range 141-697) and eGFR 24 ± 16 ml/min/1.73m2 (range 5-52), representing a mean decline in eGFR of 65%. The PPI was immediately stopped in all pts. 1 pt required temporary renal replacement therapy. 5 pts were treated with steroids. The mean ± SD most recent creatinine post diagnosis was 129.5 ± 36.5 μmol/L (range 94-196) and eGFR 41 ± 11 ml/min/1.73m2 (range=23-52). Although kidney function improved following cessation of PPI and/or treatment with steroids, there was a net decline in kidney function from pre-PPI exposure levels. CONCLUSION: PPI related AIN is an important iatrogenic cause of potentially reversible AKI and is likely to be significantly underestimated. Kidney function should be assessed in patients receiving PPI therapy presenting with non specific malaise or tiredness. AIN should be considered in patients with deteriorating kidney function when receiving PPI therapy. Prompt identification of PPI induced AIN is important as our study suggests (in line with the established literature) that cessation of therapy can at least partially reverse decline in renal function inmost patients.

M1887 The Gain in Quality-Adjusted Life Years By Switching to Esomeprazole in Those with Persistent GERD Symptoms in Primary Care: EncomPASS - a Cluster-Randomized Trial

INTRODUCTION: An increasing number of case reports have identified acute kidney injury (AKI) secondary to acute interstitial nephritis (AIN) provoked by Proton Pump Inhibitor (PPI) therapy. The present collaborative study identifies experience from a major UK renal unit. AIMS & METHODS: All cases of biopsy-proven AIN between Jan 1st 2007 and October 1st 2008 presenting to the regional renal centre (serving a population of 1.1 million), were identified. The notes of all patients (pts) with a diagnosis of AIN and a history of PPI were analysed. Pre-PPI treatment, diagnosis and most recent plasma creatinine and estimated glomerular filtration rate (eGFR) were obtained. Pts were deemed likely to have PPI-associated AKI if a deterioration in kidney function was identified after starting PPI therapy in the absence of a history of any other medications associated with AIN and other renal or systemic causes. RESULTS: 210 kidney biopsy reports were analysed of which 27 reported AIN due to a multitude of causes. Of these, 6 cases of AIN were found to be strongly associated with PPI therapy. PPI's were the most common drug class associated with AIN. Male : Female 1 : 5. The median age at diagnosis was 66 yrs (range 60-86). All pts presented with nonspecific malaise and tiredness. 5 cases were due to omeprazole & 1 pt esomeprazole. Mean ± SD duration of PPI therapy was 7.7 ± 5.6 months, (range 5-18). Mean ± SD pre-PPI creatinine was 73 ± 30 μmol/L (range 45-103); eGFR 69 ± 23 ml/min/1.73m2 (range 4590). At diagnosis, mean ± SD creatinine was 269 ± 217 μmol/L (range 141-697) and eGFR 24 ± 16 ml/min/1.73m2 (range 5-52), representing a mean decline in eGFR of 65%. The PPI was immediately stopped in all pts. 1 pt required temporary renal replacement therapy. 5 pts were treated with steroids. The mean ± SD most recent creatinine post diagnosis was 129.5 ± 36.5 μmol/L (range 94-196) and eGFR 41 ± 11 ml/min/1.73m2 (range=23-52). Although kidney function improved following cessation of PPI and/or treatment with steroids, there was a net decline in kidney function from pre-PPI exposure levels. CONCLUSION: PPI related AIN is an important iatrogenic cause of potentially reversible AKI and is likely to be significantly underestimated. Kidney function should be assessed in patients receiving PPI therapy presenting with non specific malaise or tiredness. AIN should be considered in patients with deteriorating kidney function when receiving PPI therapy. Prompt identification of PPI induced AIN is important as our study suggests (in line with the established literature) that cessation of therapy can at least partially reverse decline in renal function inmost patients.

Effect of Proton Pump Inhibitor Therapy on Inflammatory Changes in the Gastric Cardia (Carditis)

The etiology of inflammation of the gastric cardia (carditis) is controversial, and gastroesophageal reflux disease (GERD) and H. pylori infection have been proposed as etiological factors. This study aimed to investigate the effect of acid suppression on histological changes in the gastric cardia. Gastric cardia biopsies of reflux patients were evaluated at baseline and after proton pump inhibitor (PPI) therapy. The updated Sydney classification was used to score the biopsies, and carditis scores (pre- and post-PPI therapy) were compared. A total of 31 patients were included, of which 5 patients were excluded, as cardiac mucosa was not documented in either pre- or post-PPI biopsies. The mean duration of PPI therapy was 30 months (SE, 3.04 months). There was no significant change in carditis scores post-PPI therapy. The mean mononuclear and neutrophil scores were 1.23 and 0.35 pre-PPI therapy and 1.73 and 0.62 post-PPI therapy, respectively. No change in mean intestinal metaplasia and atrophy scores was identified. In conclusion, acid suppressive therapy with PPI did not lead to a significant reduction in carditis scores. These results suggest that GERD probably does not play a major role in the pathogenesis of inflammation in the gastric cardia.

Adéquation aux recommandations des prescriptions des inhibiteurs de la pompe à protons dans un service de médecine interne

Introduction Proton pump inhibitors (PPIs) are an efficient therapy, being widely used by physicians. In 2004, cost of PPIs' therapy was as high as 748 millions of euros (for The Caisse primaire d'Assurance Maladie) in France. Although validated indications of PPIs are well known, numerous un-necessary prescriptions of PPIs are common. The aim of this prospective study was to evaluate PPIs' prescriptions of patients in a department of internal medicine. Patients and methods This is a 12-week assessment of medical charts of patients, receiving PPI therapy in patients in our Department of internal medicine. Data were collected by a standardized questionnaire, with regards to: PPIs' nature and regimen, PPIs' indications as well as duration of therapy. Results The medical charts of 729 consecutive patients, with a mean age of 67 years, were collected. Two hundred (and) twenty-four patients (30.7%) received PPI therapy; 157 of these patients were given PPI before admission in our department. Omeprazole was used in 71% of patients. Duration of PPI therapy was over one year in 45% of cases. Thirty-five per cent of family physicians' PPI prescription were validated and 23.8% of those of physicians working in the department of internal medicine. The main non-conform PPI's indications, by family physicians and internists were as follows: prevention of hemorrhagic risk of anti-platelet agent (21 vs 16.4%), anticoagulant (17.8 vs 16.4%), steroids (8.3 vs 13.4%) or non-steroid anti-inflammatory therapy without risk factor (1.9 vs 9%). Finally, in patients receiving PPI therapy before admission, this therapy was maintained in 76% of cases. Conclusion This prospective study confirms the frequent prescription of PPI therapy in a department of internal medicine (31% of patients). It also underscores the importance of PPIs' use by family physicians and physicians working in a department of internal medicine; this series further highlights the difficulties to interrupt this well tolerated therapy. To date, PPI therapy should be prescribed with a cautious reweighted cost/benefit consideration.