Should we use proton pump inhibitors as an add-on treatment in hereditary hemochromatosis?
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PROVIDER: S-EPMC6284697 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Project description:Iron overload is a severe general complication of hereditary anemias. Treatment with iron chelators is hampered by important side-effects, high costs, and the lack of availability in many countries with a high prevalence of hereditary anemias. In this phase III randomized placebo-controlled trial, we assigned adults with non-transfusion-dependent hereditary anemias with mild-to-moderate iron overload to receive esomeprazole (at a dose of 40 mg twice daily) or placebo for 12 months in a cross-over design. The primary end point was change of liver iron content measured by MRI. A total of 30 participants were enrolled in the trial. Treatment with esomeprazole resulted in a statistically significant reduction in liver iron content that was 0.55 mg Fe/g dw larger than after treatment with placebo (95%CI [0.05 to 1.06]; p = 0.03). Median baseline liver iron content at the start of esomeprazole was 4.99 versus 4.49 mg Fe/g dw at start of placebo. Mean delta liver iron content after esomeprazole treatment was -0.57 (SD 1.20) versus -0.11 mg Fe/g dw (SD 0.75) after placebo treatment. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. In summary, esomeprazole resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non-transfusion-dependent hereditary anemias. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators.
| S-EPMC9325377 | biostudies-literature
Project description:Coronaviruses (CoV), discovered after 1960, caused human life-threatening outbreaks. SARS-CoV2, which appeared in Wuhan, China in December 2019, causing Severe Acute Respiratory Syndrome and has different features than other coronaviruses, has been determined and the disease caused by the virus has been called "Coronavirus Disease-2019" (COVID-19). This disease activates both the natural and acquired immune system. The cytokin storm, in which blood levels of proinflammatory cytokines are detected excessively high is developing and the uncontrolled inflammatory response causes local and systemic tissue damages. Although a spesific drug has not been found yet, the medications currently in use for other indications, whose pharmacokinetic- pharmacodynamic properties and toxic doses are already known; are included in the treatment practice of COVID-19. These drugs affect the entry of the virus into the cell and its intracellular distribution. They also have anti-inflammatory and immunomodulating effects too. Therefore, we think that Proton Pump Inhibitors (PPI's) with similar mechanisms of action may also be involved in COVID-19 treatment and prophylaxis.
| S-EPMC7834647 | biostudies-literature
Project description:To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Drug Agency.Thirty general practitioners (GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs (PPI users) and non-users (PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules.Six thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs (NSAIDS), acetylsalicylic acid (ASA), oral anticoagulant therapy (OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease (8.5%) and for the protection of gastric damage caused by NSAIDS (6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT.A substantial number of patients who apparently do not meet prescription suitability conditions can be identified, but among non PPI users on the contrary, it is possible to identify an equal number of patients for whom prescription would be suitable. Poor suitability can be identified in the population receiving OAT. Thus, there is scope for decreasing inappropriate use of PPI drugs by adhering to certain criteria and by involving all interested parties.
| S-EPMC5547376 | biostudies-other
Project description:Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials that performed pH testing in patients receiving solid-dose PPI formulations (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) for a minimum of 5 days. We used omeprazole equivalency and the surrogate biomarker, percentage time pH > 4 over a 24-hour period (pH4time), to compare PPI effectiveness for different PPIs given once, twice, or 3 times daily. We found that increasing strength of once-daily PPIs (9-64 mg omeprazole equivalents) increased pH4time linearly from approximately 10.0 to 15.6 hours; higher doses produced no further increase in pH4time. Increasing the frequency to twice-daily PPI increased pH4time linearly, from approximately 15.8 to 21.0 hours. Three-times daily PPIs performed similarly to twice-daily PPIs. The costs of PPIs varied greatly, but the cost variation was not directly related to potency. We conclude that PPIs can be used interchangeably based on potency. Using twice-daily PPIs is more effective in increasing efficacy increasing once-daily PPI dosage. Omeprazole and lansoprazole (30 mg) and 20 mg of esomeprazole rabeprazole are functionally equivalent.
| S-EPMC6913203 | biostudies-literature
Project description:AimsProton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis.MethodsA systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification.ResultsA total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having 'no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered.ConclusionsWe suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients.
| S-EPMC6046475 | biostudies-literature
Project description:BackgroundProton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients.ObjectiveWe aimed to determine the net impact of PPIs on hospital mortality among medical inpatients.DesignA microsimulation model, using literature-derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality.ParticipantsSimulated general medical inpatients outside the intensive care unit (ICU).Main measureChange in overall mortality during hospitalization.Key resultsNew initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios.ConclusionsFor the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged.
| S-EPMC4803704 | biostudies-literature
Project description:BackgroundThe use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures.MethodsWe used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years.ResultsWe matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16-3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02-2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68-12.29, p = 0.002).InterpretationUse of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.
| S-EPMC2492962 | biostudies-literature
Project description:Evidence from preclinical studies suggests a preventive effect of proton pump inhibitors (PPIs) in preeclampsia. Recently, several epidemiological studies have described a conflicting association between the use of PPIs during pregnancy and preeclampsia risk. This study aimed to evaluate the association between PPI use and the risk of preeclampsia. We searched databases, including MEDLINE, Embase, Scopus, Web of Science Core Collection, Emcare, CINAHL, and the relevant grey literature from inception until 13 September 2021. Studies reporting the preeclampsia risk with the use of PPIs were eligible for inclusion. Literature screening, data extraction, and the risk of bias assessment were performed independently by two investigators. Random-effect meta-analysis was performed to generate relative risks (RR) and 95% confidence intervals (CI). The risk of preeclampsia and preterm preeclampsia among women receiving PPIs during pregnancy were the primary outcomes of interest. This meta-analysis comprised three studies involving 4,877,565 pregnant women, of whom 119,017 were PPI users. The included studies were judged to have a low risk of bias. The risk of preeclampsia among pregnant women who received PPIs anytime during pregnancy was significantly increased (RR 1.27 (95% CI: 1.23-1.31)), although the increase was trivial in absolute terms (2 per 1000). The subgroup analysis revealed that the risk was increased in each of the three trimesters. The risk of preterm preeclampsia among pregnant women receiving PPIs anytime during pregnancy was not significantly increased (RR 1.04 (95% CI: 0.70-1.55)). The certainty evaluated by GRADE in these estimates was low. PPI use may be associated with a trivial increase in the risk of preeclampsia in pregnant women. There is no evidence supporting that PPI use decreases the risk of preeclampsia or preterm preeclampsia.
| S-EPMC9410414 | biostudies-literature
Project description:Background: This study aimed to systematically analyze the association between long-term use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). Methods: We performed a systematic search of articles on the relationship between long-term use of PPIs and the risk of GC from PubMed and EMBASE. We calculated the pooled odds ratio of GC in PPI users compared to non-PPI users using random-effects models. Results: This meta-analysis included 18 studies from 20 different databases with 4348,905 patients enrolled. In the random effects model, we found that an increased risk of GC among PPI users (OR = 1.94; 95% CI [1.43, 2.64]). The long-term use of PPIs compared with histamine-2 receptor antagonist users did not increase the risk of GC (OR = 1.65; 95% CI [0.92, 2.97]). Stratified analysis showed that PPI users had a significantly increased risk of noncardia GC (OR = 2.53; 95% CI [2.03, 3.15]), but had a relatively small relationship with the risk of gastric cardia cancer. (OR = 1.79; 95% CI [1.06, 3.03]). With the extension of PPI use time, the estimated risk value decreases (<1 year: OR = 6.33, 95% CI [3.76, 10.65]; 1–3 years: OR = 1.82, 95% CI [1.30, 2.55]; >3 years: OR = 1.25, 95% CI [1.00, 1.56]). Despite Helicobacter pylori eradication, the long-term use of PPIs did not alter the increased risk of GC (OR = 2.29; 95% CI [1.57, 3.33]). Conclusion: Our meta-analysis found that PPI use may be associated with an increased risk of GC. Further research on the causal relationship between these factors is necessary.
| S-EPMC9750528 | biostudies-literature
Project description:Background and aimsProton pump inhibitors (PPIs) are widely prescribed and have effects on gut ion absorption and urinary ion concentrations. PPIs might therefore protect against or contribute to development of kidney stones. We investigated the association between PPI use and kidney stones.MethodsWe performed a retrospective study using data from the Women's Veteran's Cohort Study, which comprised men and women, from October 1, 1999 through September 30, 2017. We collected data from 465,891 patients on PPI usage over time, demographics, laboratory results, comorbidities, and medication usage. Time-varying Cox proportional hazards and propensity matching analyses determined risk of PPI use and incident development of kidney stones. Use of histamine-2 receptor antagonists (H2RAs) was measured and levothyroxine use was a negative control exposure.ResultsPPI use was associated with kidney stones in the unadjusted analysis, with PPI use as a time-varying variable (hazard ratio [HR], 1.74; 95% CI, 1.67-1.82), and persisted in the adjusted analysis (HR, 1.46; CI, 1.38-1.55). The association was maintained in a propensity score-matched subset of PPI users and nonusers (adjusted HR, 1.25; CI 1.19-1.33). Increased dosage of PPI was associated with increased risk of kidney stones (HR, 1.11; CI, 1.09-1.14 for each increase in 30 defined daily doses over a 3-month period). H2RAs were also associated with increased risk (adjusted HR, 1.47; CI 1.31-1.64). We found no association, in adjusted analysis, of levothyroxine use with kidney stones (adjusted HR, 1.06; CI 0.94-1.21).ConclusionsIn a large cohort study of veterans, we found PPI use to be associated with a dose-dependent increase in risk of kidney stones. H2RA use also has an association with risk of kidney stones, so acid suppression might be an involved mechanism. The effect is small and should not change prescribing for most patients.
| S-EPMC7483196 | biostudies-literature