PMID: 

Dose Response. 2019 Apr-Jun;17(2):1559325819843383. Epub 2019 May 2. PMID: 31080379

Abstract Title: 

Association of Increased Risk of Pneumonia and Using Proton Pump Inhibitors in Patients With Type II Diabetes Mellitus.

Abstract: 

Background: This study explored the possible association between the use of proton pump inhibitors (PPIs) and the increased incidence of pneumonia in patients with type 2 diabetes mellitus (T2DM).Methods: We selected 4940 patients with T2DM of whom 988 and 3952 were enrolled in PPI and propensity score-matched control cohorts, respectively. All patients were followed from the index date until admission with pneumonia, withdrawal from the National Health Insurance program or the end of 2013. The PPIs associated with risk of incident pneumonia were examined. Furthermore, we assessed the risk of pneumonia according to annual defined daily doses in the PPI cohort.Results: After a 14-year follow-up, the cumulative incidence of pneumonia in the PPI users was 11.4% higher than that in the controls (30.3% vs 18.9%). Compared to the controls, the PPI users had a 1.70-fold higher risk of pneumonia in the Cox proportional hazards model after adjustment for matched pairs. The risk of pneumonia increased with the annual PPI defined daily dose.Conclusion: The results of this population-based retrospective cohort study suggest that PPI use increased the risk of pneumonia in patients with T2DM. The effects were more prominent in patients administered higher doses of PPIs.

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PMID: 

J Gastroenterol. 2019 Jun 11. Epub 2019 Jun 11. PMID: 31187275

Abstract Title: 

Effects of proton pump inhibitor use on risk of Clostridium difficile infection: a hospital cohort study.

Abstract: 

BACKGROUND: Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed studies analyzing the effects of PPI use on CDI risk are lacking. The present study investigated the association of the dose, duration, and types of PPIs with CDI risk.METHODS: A single-center, cohort study was conducted on patients admitted to a hospital. The exposed cohort comprised patients who were prescribed PPIs at least once during the study period, and a control cohort was prepared by randomly assigning an index date to patients who did not use PPIs ensuring the same distribution of index dates as in the exposed cohort and matching sex, age, hospitalization period, and date of admission.RESULTS: PPI use increased the risk of CDI by 1.8-fold [95% confidence interval (CI) 1.5-2.2]. CDI risk increased by 1.8-fold with esomeprazole (95% CI 1.4-2.2) and 2.0-fold with pantoprazole (95% CI 1.5-2.8). Patients who used a high dose had a higher risk than those who used a medium dose [adjusted hazard ratio (HR) 2.0 vs 1.3]. The risk of CDI increased 4.2-fold when the PPI exposure period was 6 days or shorter than 6 days.CONCLUSIONS: Our study showed that PPI use was associated with an increased risk of developing CDI and the risk of CDI was dose dependent. Therefore, PPIs should only be used at proper doses and only for the necessary indications to avoid CDI risk.

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PMID: 

World J Gastroenterol. 2019 Jun 14 ;25(22):2706-2719. PMID: 31235994

Abstract Title: 

Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified.

Abstract: 

Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.

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PMID: 

QJM. 2019 Jun 28. Epub 2019 Jun 28. PMID: 31251364

Abstract Title: 

Proton Pump Inhibitor Use and Progression to Major Adverse Renal Events: A Competing Risk Analysis.

Abstract: 

BACKGROUND: Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD).AIM: To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD.DESIGN: Observational cohort study comprising patients with CKD attending secondary care renal clinics from 01/01/2006 until 31/12/2016.METHODS: We collated baseline clinical, socio-demographic and biochemical data at start of PPI (PPI group) or study inception (control group). MARE was considered a composite of doubling of creatinine or end stage renal disease. Association between PPI exposure and progression to MARE was assessed by cause-specific hazards competing risk survival analysis.RESULTS: There were 3,824 patients with CKD included in the analyses of whom 1,195 were prescribed a PPI. The PPI group was younger (64.8 vs 67.0 years, p 

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PMID: 

World J Hepatol. 2019 Jun 27 ;11(6):522-530. PMID: 31293720

Abstract Title: 

Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients.

Abstract: 

BACKGROUND: Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE.AIM: To investigate the relationship between the use of proton pump inhibitors (PPIs) and HE in patients with cirrhosis.METHODS: This is a single center, retrospective analysis. Patients were included in the study with an admitting diagnosis of HE. The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria. The primary outcome of the study was to evaluate the grade of HE in PPI usersnon-users at admission to the hospital and throughout their hospital course. Secondary outcomes included rate of infection, gastrointestinal bleeding within the last 12 mo, mean ammonia level, and model for end-stage liver disease scores at admission.RESULTS: The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group (0.001). The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers (0.046). Twenty-seven (31.8%) patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group (16.7%) (0.138). Finally, 10 (11.8%) patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group (2.8%) (0.220).CONCLUSION: Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.

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PMID: 

Fed Pract. 2019 Jun ;36(Suppl 4):S27-S31. PMID: 31296980

Abstract Title: 

Proton Pump Inhibitor Use and Risk of Dementia in the Veteran Population.

Abstract: 

There was a statistically significant association between use of proton pump inhibitors and dementia diagnosis in a 11-year retrospective study of patients at the Sioux Falls Veteran Affairs Health Care System.

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PMID: 

Scand J Gastroenterol. 2019 Jul 30:1-9. Epub 2019 Jul 30. PMID: 31361979

Abstract Title: 

The impact of proton pump inhibitors on the intestinal microbiota in chronic hepatitis C patients.

Abstract: 

Proton pump inhibitors (PPI), a class of drugs commonly used, are known to be associated with changes in the intestinal microbiota. Published studies were done in heterogeneous cohorts which could hamper conclusions drawn as effects of diseases were not taken into consideration. We aimed to elucidate differences in the intestinal microbiota being associated to the use of PPI in a cohort study of patients with chronic hepatitis C.The 16S rDNA gene was analyzed in stool samples of patients with and without PPI use. Patients with concomitant medication influencing the microbiota were excluded. Results were compared with the clinical course of hepatitis C patients with decompensated liver cirrhosis.No differences in alpha diversity could be observed, while the microbial community structure differed significantly, especially in patients with liver cirrhosis. The relative abundance of.,. and. was significantly increased in patients with PPI use irrespectively of the stage of liver disease. Finally, in patients with decompensated liver cirrhosis due to chronic HCV infection only in these using PPI bacterial phylotypes were isolated.PPI use was associated with significant alterations in the microbial community in patients with chronic hepatitis C, which were even pronounced in patients with liver cirrhosis. In patients with decompensated liver cirrhosis due to chronic HCV infection, the use of PPI may promote infections either directly or indirectly through changes in the microbial community structure. Future studies should further investigate long-term impact on the microbiota and the clinical outcome.

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PMID: 

Cancer Epidemiol. 2019 Aug 21 ;62:101585. Epub 2019 Aug 21. PMID: 31445426

Abstract Title: 

Duration of use of proton pump inhibitors and the risk of gastric and oesophageal cancer.

Abstract: 

BACKGROUND: There is increasing interest in the potential association between proton pump inhibitors (PPIs) and the risk of gastric and oesophageal cancer, yet the effect of duration of treatment needs clarification.METHODS: This Swedish population-based cohort study assessed the influence of time since initiation of PPI treatment on the risk of gastric and oesophageal cancer, presented as standardised incidence ratios and 95% confidence intervals.RESULTS: The risk of gastric and oesophageal cancer during the first year was 7-10 times higher than the background population, and remained 24-202% increased without any decrease over time after the first year.CONCLUSION: PPI use was associated with an increased risk of gastric and oesophageal cancer and the risk remained increased over follow-up. These results support our original hypothesis that use of PPIs may be a risk factor for gastric and oesophageal cancer in the general population of maintenance users, independent of underlying indications.

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PMID: 

Aliment Pharmacol Ther. 2019 Aug 25. Epub 2019 Aug 25. PMID: 31448440

Abstract Title: 

Use of proton pump inhibitors and risk of cholangitis: a nationwide cohort study.

Abstract: 

BACKGROUND: Proton pump inhibitor (PPI) use may alter the gut microbiome and increase the risk of cholangitis. However, the association of PPI use with the risk of incident cholangitis has not been evaluated.AIM: To evaluate whether PPI use was associated with a higher risk of cholangitis.METHODS: This cohort study included a nationwide representative sample of the Korean general population followed up for 10 years (1 January 2003 to 31 December 2013). PPI use was identified from treatment claims and considered as a time-varying variable. Incident cholangitis was identified from hospitalisation and out-patient visit claims.RESULTS: During 4 212 003 person-years of follow-up, 58,863 participants had at least one PPI prescription and 1 834 participants developed cholangitis. The age-, sex-, residential area- and income-adjusted hazard ratio (HR) for incident cholangitis comparing PPI use with non-use was 6.06 (95% CI, 4.64-7.91). Theassociation was essentially unchanged in fully adjusted models (HR 5.75; 95% CI, 4.39-7.54). The risk was highest during PPI treatment and decreased gradually after PPI discontinuation (P 

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PMID: 

Eur J Gastroenterol Hepatol. 2019 Aug 27. Epub 2019 Aug 27. PMID: 31464790

Abstract Title: 

Deleterious effect of proton pump inhibitors on the disease course of cirrhosis.

Abstract: 

OBJECTIVES: Proton pump inhibitors(PPIs) are widely prescribed to patients with liver cirrhosis. We hypothesized that long-standing PPI use is associated with spontaneous bacterial peritonitis(SBP) and accelerated development of disease-specific complications and liver-related death.METHODS: A 5-year follow-up observational cohort study assessed the impact of long-standing PPI use on the clinical course of cirrhosis in a large referral patient cohort. Three hundred fifty patients with cirrhosis (alcohol:69.1%, Child-Pugh stage A/B/C:206/108/36) were assigned to two groups: regular PPI users (n=196) and nonusers (n=154). Occurrence of SBP, decompensation events (ascites, hepatic encephalopathy and variceal bleeding), and liver-related death were assessed.RESULTS: Regular PPI use was associated with an increased cumulative probability of SBP compared to nonusers [55% vs. 24.8%, hazard ratio(HR):4.25; P=0.05], in patients without previous SBP episode (n=84). A similar association was found between regular PPI use and decompensation events. The risk of the development of a first decompensation was higher in regular PPI users compared with nonusers, in patients with compensated clinical stage at enrollment (HR: 2.81, P= 0.008, n=146). The risk of liver-related death was also significantly increased among regular PPI users (P

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