Duration Of Proton Pump Inhibitors Use Research Articles

Proton pump inhibitors are not associated with fundic gland polyps - a systematic review that takes into consideration all known confounders.

Sporadic fundic gland polyps (FGPs) progress, albeit rarely, to dysplasia and cancer. Two meta-analyses, including 8 and 11 studies, concluded that proton pump inhibitors (PPIs) were associated with FGPs. Intervention is considered unnecessary when FGPs have a background of PPIs use. Both meta-analyses, however, disregarded known confounders: age, sex, endoscopy indications, study design (prospective or retrospective), duration of PPI use, and H. pylori infection. Confounders are known to invalidate meta-analyses. We followed PRIXMA guidelines and searched the literature for studies on FGPs in PPI-users and PPI-nonusers. In the 22 studies searched, we compared FGPs in PPI-users (n = 6534) and PPI-nonusers (n = 41 115). Heterogeneity was significant (Cochran Q = 277.8, P < 0.0001; I2 = 92.8%), annulling meta-analysis performed by blanket tallying. To offset the above confounders, we matched PPI-users and PPI-nonusers by (a) age and sex (n = 4300 and 29 307, respectively) and (b) their propensity scores derived from the confounders (n = 2950 and 4729, respectively). After both matching, FGPs were not significantly different between PPI-users and PPI-nonusers [odds ratio (OR) = 1.1, P = 0.3078; OR = 0.9, P = 0.3258, respectively]. Furthermore, FGP frequency did not correlate with increasing duration of PPI use (Pearson and Spearman correlation coefficients = 0.1162, 0.0386, P < 0.6064, 0.8646, respectively); it was not significantly different between any of the duration periods of observation, namely, <10, 10-20, 20-40, >40 months, nor was it significantly different between PPI-users and PPI-nonusers within each duration period (P > 0.05). We conclude that PPIs are not associated with FGPs, implying that a background history of PPI use is not a justification for nonintervention in the management of FGPs.

Associations between Proton-Pump Inhibitor Usage, Allergy, and Asthma: An Analysis of NHANES 2005–2006

Introduction: Acid suppression medications, such as proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists, are commonly prescribed for the treatment of gastroesophageal reflux disease and other gastrointestinal disorders. However, concerns regarding potential long-term side effects are brought up by the overuse of PPIs. This study aimed to investigate the relationship between PPI usage, allergy, and asthma in the general US population. Methods: Data of individuals aged ≥20 years who had information on PPI use and questionnaires on allergy and asthma in the US National Health and Nutrition Examination Survey (NHANES) 2005–2006 were analyzed. Univariate and multivariable logistic regression analyses were performed to determine the associations between PPI use, prevalent allergy, and asthma. Results: A total of 4,481 participants (representing 198,543,007 US individuals after weighting) were included in the analyses. PPI use was not significantly associated with the presence of allergy or asthma in the general study population after adjustment. However, in females without steroid exposure, PPI use was significantly associated with increased odds of allergy (adjusted odds ratio [aOR] = 1.69, 95% confidence interval [CI]: 1.002–2.86), among which esomeprazole use was significantly associated with increased odds of allergy (aOR = 2.68, 95% CI: 1.30–5.54) and lansoprazole with increased odds of asthma (aOR = 3.44, 95% CI: 1.50–7.87) as compared to no PPI use. Duration of PPI use was not significantly associated with allergy or asthma. Conclusions: In US women without steroid exposure, PPI use is associated with increased likelihood of prevalent allergy and asthma.

Association between the Use of Proton Pump Inhibitors and Cardiovascular Diseases: A Nested Case-Control Study Using a National Health Screening Cohort.

We investigated the association of proton pump inhibitor (PPI) use with the risk of stroke and ischemic heart disease (IHD). The Korean National Health Insurance Service-Health Screening cohort from 2002 to 2003, the participants of which were followed up until 2019, was used. In study I, 45,905 participants who were diagnosed with stroke were matched with 91,810 control I participants. The history of PPI medication was examined. In study II, 40,928 participants who were diagnosed with IHD were matched with 81,856 control II participants. In both study I and study II, the previous history of PPI medication was examined. A propensity score overlap-weighted multivariable logistic regression analysis was conducted to estimate the overlap-weighted odds ratios (ORs) of PPI use for stroke (study I) and IHD (study II). Current PPI use was linked with higher odds for stroke in study I. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 0.96 [95% CI = 0.92-1.00] < 1.55 [1.50-1.61] < 1.62 [1.57-1.68] for < 30 days, 30 to 180 days, and ≥180 days of PPI use). Previous PPI use was linked with higher odds for IHD in study II. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 1.13 [95% CI = 1.08-1.18] < 2.12 [2.04-2.21] < 2.60 [2.51-2.69] for <30 days, 30 to 180 days, and ≥180 days of PPI use). Current PPI medication is associated with a high risk of stroke and IHD. A longer duration of PPI medication was related to a higher risk of stroke and IHD. However, a prior history of PPI medication was not linked with a high risk of stroke or IHD.

Proton Pump Inhibitors: Adversaries In Our Fight Against Antibiotic Resistance?

Madam, The proton-pump inhibitors (PPIs) belong to a class of medications that reduce stomach acid production by irreversibly inhibiting the stomach's H+/K+ ATPase pump. These medications are used in the treatment of many conditions, such aspeptic ulcer, gastroesophageal reflux, as part of H. Pylori eradication, gastrinomas, Barrett’s oesophagus and many other conditions. They are considered to be the most potent inhibitors of acid secretion, and have largely supplanted the H2 receptor antagonists and antacids. They are also among the most widely sold medications worldwide. The class of proton pump inhibitors is listed on WHO’s list of essential medicines.1Proton pump inhibitors are generally well tolerated. However, headache, nausea, diarrhoea, abdominal pain, fatigue, and dizziness are identified as some of the common side effects. Due to their efficacies and low risk profile, PPIs are often prescribed for extend than required period. Several recent studies have shown that long-term PPI use is associated with various adverse outcomes. A 2023 study published in JAMA Network Open demonstrated that long-term use of PPIs may lead to an increased risk of acquiring extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing enterobacterales.2Another study3 published in 2022 showed that PPI use was the only modifiable factor associated with the carriage of ESBL producers in residents of long-term care facilities. These studies add to the expanding list of adverse outcomes associated with PPIs. Other adverse events of long-term PPI use, include the risk of fractures, pneumonia, Clostridium difficile diarrhoea, hypomagnesaemia, vitamin B12deficiency, chronic kidney disease, and dementia.4 Proton pump inhibitors are still used widely in Pakistan. These new findings are concerning as ESBL-producing Enterobacteriaceae are highly prevalent in Pakistan. A meta-analysis showed that the overall pooled proportion of ESBLs in Pakistan is 40%5 whereas the German population showed an estimated ESBL proportion in the range of 10 to 15% and a US census reported 4 to 12% resistance due to ESBLs.5 This calls for a strict prescription control of PPIs by Pakistani physicians, and the duration of PPI use should not extend for longer than needed. In addition, the practice of PPI’s over the counter sale by the pharmacists in Pakistan should be stopped. Additional precautions should be taken in hospitalized patients who are using PPIs to prevent them from getting multi-drug resistant infections.

Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease.

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients.

The association between duration of and indications for proton pump inhibitor use and risk of gastric polyps.

The development of fundic gland polyps (FGPs) is the most common side effect of long-term proton pump inhibitor (PPI) use; however, the effect of drug use characteristics and their impact on the risk of other gastric polyp development remain unclear. We aimed to identify the influence of PPI administration, as well as its duration and dose, in the development of gastric polyps. A prospective cohort study was conducted on consecutive patients who underwent gastroscopy between September 2017 and August 2019. Detailed characteristics of gastric polyps, Helicobacter pylori infection, and PPI use were analyzed. Among the 2723 patients included, gastric polyps (75% FGPs, 22% hyperplastic) were detected in 16.4%, and 60% were prescribed PPI. The risk of FGPs and hyperplastic polyps according to the duration of PPI use were as follows: 2-5 years [odds ratio (95% confidence interval); 2.86 (2.00-4.11) and 2.82 (1.69-4.78)]; 6-9 years [7.42 (5.03-11.01) and 2.32 (1.05-4.78)]; ≥10 years [14.94 (10.36-21.80) and 3.52 (1.67-7.03)]. Multivariate analysis confirmed that the risk of FGPs was 17.16 (11.35-26.23) for ≥10 years of PPI use. Portal hypertension-related conditions were associated with hyperplastic polyps [4.99 (2.71-9.20)]. Duration of and indications for PPI use are the most predictive factors for the development of gastric polyps. Prolonged PPI use increases the risk of polyp development and the number of patients with polyps, which may burden endoscopic practice. Highly selected patients may require particular care despite minimal risk of dysplasia and bleeding generally.

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients: Results From the TransplantLines Biobank and Cohort Study

Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Cross-sectional study. Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. PPI use, PPI type, PPI dosage, and duration of PPI use. Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Logistic and linear regression. We included 937 kidney transplant recipients (mean age 56±13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P<0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P<0.001), lower physical HRQoL (regression coefficient-8.54, 95% CI,-11.54 to-5.54, P<0.001), and lower mental HRQoL (regression coefficient-4.66, 95% CI,-7.15 to-2.17, P<0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Residual confounding and inability to assess causal relationships. PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted.

Proton Pompası İnhibitörleri ile Potansiyel İlaç Etkileşimlerinin Değerlendirilmesi: Retrospektif Bir Çalışma

Objective: Proton pump inhibitors (PPIs) are the most prescribed gastrointestinal system medications and are often prescribed together with other medications. This may lead to drug interactions. In our study, it was aimed to determine the possible interactions of PPIs. Material and Methods: This retrospective study was conducted between January 1, 2021 and March 31, 2021. A prescription review was conducted in a community pharmacy in İstanbul and potential drug interactions were evaluated using the Medscape and Lexicomp databases. Results: A total of 114 prescriptions were reviewed. The mean age of the patients was 55.1±14.8 years, and the mean duration of PPIs use was 5 months. It was determined that the one who prescribed PPIs the most was the family physician and it was prescribed most frequently with the indication of gastroesophageal reflux disease. The total number of interactions in the prescriptions was determined as 248 in the Medscape database and 295 in the Lexicomp database (p<0.05). Pantoprazole was found to be the most interacting PPIs in both databases. Levothyroxine was found to be the drug that interacted most with PPIs in both databases. Age and duration of PPIs use were found to be positively significantly correlated (p<0.05). Conclusion: In our study, the number of potential drug interactions in prescriptions containing PPIs was found to be high. We think that the possible interactions and duration of use of drugs used due to comorbid diseases should be considered in prescriptions containing PPIs.

Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review and meta-analysis.

Proton pump inhibitors (PPIs) may be associated with gastric cancer, but studies in recent years have proven still inconsistent results. We conducted a systematic review and meta-analysis to investigate the association between PPI use and gastric cancer. Pubmed, EMBASE, and Cochrane library were searched for studies published up to 15th February 2022. Studies on the association between PPI and the risk of gastric cancer, pooled the odds ratios (ORs) using a random-effects model. The subgroup analysis for study design, site of gastric cancer, and the duration of PPI use was performed. Heterogeneity was assessed using the I2 and Cochran's Q statistics. Sixteen cohorts and case-control studies were included. PPI use was significantly associated with gastric cancer (OR: 1.75, 95% CI: 1.28-2.40). The subgroup analysis found a significant risk increase in non-cardia gastric cancer (OR: 2.14, 95%CI: 1.50-3.07). There was no duration-dependent effect of PPI use and gastric cancer risk (< 1year: OR: 2.56, 95% CI: 1.41-4.64, I2 = 98%; 1-3years: OR: 1.47, 95% CI: 1.26-1.71, I2 = 41%; > 3years: OR: 1.58, 95% CI: 1.16-2.14, I2 = 74%). PPIs were significantly associated with an increased risk of gastric cancer. However, this association does not confirm causation. Several well-design studies are needed to confirm the findings in the future.

Association between Urolithiasis and History Proton Pump Inhibitor Medication: A Nested Case-Control Study.

A few retrospective studies have suggested the risk of urolithiasis associated with the use of proton pump inhibitors (PPIs). The current research intended to estimate the risk of urolithiasis according to previous PPI use. A nested case-control study was conducted using the National Health Insurance Service-National Health Screening Cohort in Korea. A total of 28,962 patients with urolithiasis and 115,848 control participants were selected. The previous prescription history of PPI with days of PPI prescription was collected. To calculate the odds ratios (OR) of past, current, and days of PPI use for urolithiasis, logistic regression models were used. Subgroup analyses were conducted. The urolithiasis group demonstrated a higher rate of current PPI users than the control group (60.9% vs. 43.7%). The current PPI users indicated 2.49 times higher odds for urolithiasis than no PPI users (95% confidence intervals [CI] = 2.33–2.66). A longer duration of PPI use was associated with greater odds for urolithiasis (adjusted OR = 1.65 (95% CI = 1.54–1.77) < 1.97 (95% CI = 1.84–2.11) < 2.32 (95% CI = 2.14–2.49) for 1–19 days, 30–364 days, and 365 or more days of PPI prescription). All subgroup analyses described a consistently positive association of previous PPI use with urolithiasis. Prior PPI use was related to a higher risk of urolithiasis. The relationship between previous PPI use and urolithiasis demonstrated a dose-response association.

Adverse event profiles of hypomagnesemia caused by proton pump inhibitors using the Japanese Adverse Drug Event Report (JADER) Database.

Proton pump inhibitors (PPIs) are commonly used for the prevention or treatment of gastric ulcers, but they can induce hypomagnesemia. Little is known about the onset duration and risk factors related to patient characteristics of this adverse event in Japanese patients. Therefore, we analyzed the time-to-onset of PPI-induced hypomagnesemia and evaluated the association between hypomagnesemia and PPIs using the Japanese Adverse Drug Event Report (JADER) database. We analyzed hypomagnesemia cases between 2004 and 2021. The time-to-onset analysis was performed using the Weibull distribution, and the adjusted reporting odds ratio (aROR) or 95% confidence interval (95% CI) was calculated using a multiple logistic regression analysis. The analysis database comprised 236,525 cases, with 188 cases associated with hypomagnesemia. The median onset duration (interquartile range) of PPI-induced hypomagnesemia was 99.0 (51.8-285.5 ) days, which is considered the random failure type. The multiple logistic regression analysis revealed that hypomagnesemia is significantly associated with male sex (aROR, 95% CI: 1.66, 1.23-2.25) , age < 60 (1.59, 1.14-2.21) , estimated body-mass index (eBMI) (0.94, 0.91-0.98) , PPIs (1.66, 1.18-2.30) , and the interaction of age (<60)*PPIs (1.58, 1.13-2.19) . However, diuretics were not significantly associated with hypomagnesemia. Our results suggest that serum magnesium levels should be measured regularly regardless of the duration of PPI use, especially in patients with male sex, age < 60, or low BMI. These findings will assist health professionals in the adequate use of PPIs. These findings need to be evaluated by cohort studies and long-term clinical investigations.

Association between Benign Paroxysmal Positional Vertigo and Previous Proton Pump Inhibitor Use: A Nested Case-Control Study Using a National Health Screening Cohort.

The present nested case–control study evaluated the impact of previous proton pump inhibitor (PPI) prescription on the risk of benign paroxysmal positional vertigo (BPPV). A ≥40-year-old Korean population was included. A total of 34,441 patients with BPPV was matched with 137,764 comparison participants for demographic and socioeconomic factors. Previous histories of PPI use and PPI prescription dates were compared between the BPPV and comparison groups. The odds ratios (ORs) with 95% confidence intervals (CIs) of PPI use for BPPV were calculated using a logistic regression. The demographic and socioeconomic factors and comorbidities were adjusted in the adjusted model. Both current and past PPI users were associated with higher odds for BPPV than non-PPI users (adjusted OR (aOR) = 3.57, 95% CI = 3.33–3.83, and p < 0.001 for current PPI users and aOR = 1.76, 95% CI = 1.64–1.89, and p < 0.001 for past PPI users). In addition, longer dates of PPI use were related to higher odds for BPPV (aOR (95% CI) = 1.95 [1.81–2.10] for ≥1 day and <30 days of PPI prescription, <2.88 [2.68–3.10] for ≥30 days and <365 days of PPI prescription, and <3.45 [3.19–3.73] for ≥365 days of PPI prescription). PPI use was linked with an elevated risk of BPPV in the adult population. The odds for BPPV were higher in patients with a longer duration of PPI use.

Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality

The use of proton pump inhibitors (PPIs) has increased rapidly in the past 2 decades. Concerns about the regular use of PPIs contributing to mortality have been raised. We conducted a prospective cohort study using data collected from the Nurses' Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018). Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for mortality according to PPI use. We used a modified lag-time approach to minimize reverse causation (ie, protopathic bias). Among 50,156 women and 21,731 men followed for 831,407 person-years and a median of 13.8 years, we documented 22,125 deaths, including 4592 deaths from cancer, 5404 from cardiovascular diseases, and 12,129 deaths from other causes. Compared with nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality (HR, 1.19; 95% CI, 1.13-1.24) and mortality due to cancer (HR, 1.30; 95% CI, 1.17-1.44), cardiovascular diseases (HR, 1.13; 95% CI, 1.02-1.26), respiratory diseases (HR, 1.32; 95% CI, 1.12-1.56), and digestive diseases (HR, 1.50; 95% CI, 1.10-2.05). Upon applying lag times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97-1.11; cancer: HR, 1.07; 95% CI, 0.89-1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81-1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95-1.50; digestive diseases: HR, 1.38; 95% CI, 0.88-2.18). Longer duration of PPI use did not confer higher risks for all-cause and cause-specific mortality. After accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes.

Proton pump inhibitor use and risk of depression and anxiety in children: nationwide cohort study.

Although some data have linked proton pump inhibitor (PPI) use to risk of depression and anxiety, there are no studies investigating this safety issue in children. This study investigated the association between PPI use and risk of depression and anxiety in children. We conducted a nationwide register‐based cohort study in Sweden, July 1, 2007, to December 31, 2016. Following matching on age and propensity score, we included 29,320 pairs of PPI initiators and noninitiators among children aged 7–17 years old. The primary analysis examined the risk of incident depression and anxiety, a composite outcome defined as a diagnosis of depression, anxiety, or a prescription for an antidepressant. Children who initiated PPI use had higher hazards for risk of depression and anxiety compared with noninitiators (hazard ratios [HRs], 2.61; 95% confidence interval [CI], 2.32–2.94). In analyses of the timing of depression and anxiety onset after PPI initiation, the HRs were 3.71 (95% CI, 2.17–6.34) for 1–30 days, 3.47 (95% CI, 2.33–5.18) for 31–90 days, 2.71 (2.04–3.60) for 91–180 days, 2.52 (2.00–3.16) for 181–365 days, and 2.34 (1.94–2.82) for 366–730 days. Significant associations were observed across all age groups. The magnitude of the association increased with longer duration of PPI use (p for trend < 0.0001). The association was consistent through all sensitivity analyses, including high‐dimensional propensity score matching (HR, 2.31, 95% CI, 2.05–2.61). PPI use was associated with increased risk of depression and anxiety in children. Further investigation is warranted to confirm or refute this potential association.

Diabetic Nephropathy and Proton Pump Inhibitors - Pilot Case-Control Study.

Introduction:Proton pump inhibitors (PPIs) are liberally used over the counter medication and is largely considered safe. Off late, there are many reports that suggest increased incidence of chronic kidney disease with long-term PPI use. PPIs are often prescribed in patients with diabetes mellitus (DM) and one of the well-known complications of DM is diabetic nephropathy (DN). Thus, the aim of our study was to evaluate association between PPI use and DN.Methods:It was a case-control study conducted over a 2-year period (April 2017–March 2019). Cases were outpatients with type II DM and associated DN. Controls were age and sex-matched type II DM without DN.Results:A total of 200 participants, 100 each in the case and control group, were recruited. The proportion of participants using PPI was 62% in the cases and 42% in the controls (P = 0.005). The most common PPI used was pantoprazole. Increased duration of PPI use was significantly associated with DN [adjusted odds ratio: 1.171; 95% confidence interval: 1.022, 1.341; P = 0.023].Conclusion:There is a significant association between the use of PPIs and DN in patients with type II DM. Since PPIs have other beneficial effects in patients with DM such as glycaemic control and relief from gastro-oesophageal symptoms, need for risk benefit assessment for long-term use of PPIs in DM is warranted.

No association between acid suppressant use and risk of dementia: an updated meta-analysis.

Findings from large observational studies on whether the use of acid suppressants increases the risk of dementia have been inconsistent. Since proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are the most commonly used acid suppressants in clinical practice, we performed a meta-analysis to examine the influence of PPI and H2RA on the risk of dementia. A systematic search was performed on the PubMed, EMBASE, and Cochrane Library databases to identify studies published up to April, 2021. Studies that reported adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the associations of interest were included. Data in the included studies were pooled using the random-effects model for meta-analysis. Statistical analysis was performed using Stata version 12.0 software. Seventeen studies involving 1,251,562 participants were included. It was found that PPI users were not likely to develop dementia compared with those not taking PPI (HR = 0.98, 95% CI: 0.85-1.13). Subgroup analysis based on publication year, location, mean age, duration of PPI use, and female proportion also revealed no association between PPI use and dementia risk. Similarly, H2RA use was not associated with the risk of dementia, as indicated by the pooled HR of 1.20 (95% CI: 0.98-1.47). Results of this meta-analysis suggest that PPI and H2RA do not increase the risk of dementia. These results may be used to inform the clinical application of acid suppressants. However, further randomized controlled trials are needed to confirm the present conclusions.

Prolonged Use of Proton Pump Inhibitors, but Not Histamine-2 Receptor Antagonists, Is Associated With Lower Bone Mineral Density in Males Aged Over 70.

Aims: The association of acid suppressants use with bone mineral density (BMD) is still unclear, especially in older adult with prolonged use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). In this study, our aim was to investigate the association between PPI or H2RA use and BMD in general US older adults.Methods: We conducted a cross-sectional study on a sample from National Health and Nutrition Examination Survey. Association between long-term use of PPIs or H2RAs and lumber spine BMD in elderly was evaluated using weighted multivariate linear regression models. Sensitive and subgroup analysis were also performed in this study.Results: Long-term PPI use is correlated with lower lumber spine BMD in our multivariable regression model after adjusting for known confounding factors. Further analysis showed PPI use with a duration over 1 year was negatively associated with lumber spine BMD in male, elderly aged over 70 years, and white elderly. There is no significant association between long-term H2RA use and lumber spine BMD.Conclusions: Our results indicated that the association between long-term use of PPI and lumber spine BMD differed by gender. Long term use of PPIs would reduce lumber spine BMD in older men, while H2RA use is not significantly linked with lumber spine BMD. Patients that are at high risk of bone loss should shortened the duration of PPI use (<1 year) or use H2RAs as alternative if possible.

Proton pump inhibitors and risk of colorectal cancer

ObjectiveTo determine whether proton pump inhibitors (PPIs) are associated with an increased risk of colorectal cancer, compared with histamine-2 receptor antagonists (H2RAs).DesignThe United Kingdom Clinical Practice Research Datalink was used...

Association between Proton Pump Inhibitors and Hearing Impairment: A Nested Case-Control Study.

This study investigated the association of previous use of proton pump inhibitors (PPIs) with the rate of hearing impairment. The ≥40-year-old population in the Korean National Health Insurance Service-Health Screening Cohort was enrolled. The 6626 registered hearing-impaired patients were matched with 508,240 control participants for age, sex, income, region of residence, and index date (date of hearing impairment diagnosis). The prescription histories of PPIs were collected for 2 years before the index date. The odds ratios of the duration of PPI use for hearing impairment were analyzed using conditional logistic regression. Subgroups of age/sex and severity of hearing impairments were additionally analyzed for the relation of PPI use with hearing impairment. PPI use for 30–365 days was associated with a 1.65-times higher odds of hearing impairment (95% confidence interval (CI) = 1.47–1.86 for 30–365 days of PPI medication). PPI use for ≥365 days was also related to 1.52-times higher odds of hearing impairment (95% CI = 1.35–1.72, p < 0.001). All age and sex subgroups demonstrated a positive association between PPI use and hearing impairment. Severe hearing impairment showed consistently higher odds of a relation with PPI use. PPI use was associated with an increased rate of hearing impairment.

Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea

ObjectiveThe association between proton pump inhibitor (PPI) use and gastric cancer related to Helicobacter pylori eradication has not been fully investigated in geographical regions with high risk of gastric cancer....