Long-term Proton Pump Inhibitors Research Articles

Long-Term Proton Pump Inhibitor Therapy and its Effect on Endocrine Hormones in Selected Patient Population.

To evaluate the impacts of long-term utilization of proton pump inhibitors on male reproductive hormones and its clinical outcomes. A cross-sectional study was performed in two out-patients gastroenterology clinics in Khyber Pakhtunkhwa province. Male patients who were using proton pump inhibitors regularly for ≥3 months were enrolled in this study. Among 65 enrolled participants, patients with sexual complaints have significant variations in mean serum levels of prolactin (p<0.001), sex hormone binding globulins (p=0.043), total testosterone (p<0.001) and progesterone (p=0.001) as compared to patients without sexual complaints. Significantly high values of prolactin mean ranks were observed in patient with sexual complaints (p<0.001). There were statistically significant correlations of serum levels of sex hormone binding globulins (p=0.003), total testosterone (p=0.008) and progesterone (p<0.001) with serum prolactin levels. Similarly, statistically significant variation was observed for decreased libido(p=0.001), erectile dysfunction (p=0.001) and decreased semen mass ((p<0.001) between normal and hyperprolactinemic PPI users. Highly significant differences were observed in serum sex hormone binding globulins (p<0.001), total testosterone (p<0.001) and progesterone (p<0.001) values in normal and hyperprolactinemic groups. Long-term utilization of PPI may induce endocrine hormone disruption with subsequent sexual complications.

Updates on Surgical Treatment for Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common condition that is on the rise. Obesity is one risk factor that has increased in parallel with the rise of GERD. Typical symptoms include heartburn, regurgitation, dysphagia, cough, and chest pain. Patients with typical symptoms are empirically treated with proton pump inhibitors (PPIs). If the diagnosis is not clear, further evaluation is performed with endoscopy, pH monitoring, and esophageal manometry. Untreated GERD increases the risk of esophagitis, esophageal stricture, Barrett's esophagus, and esophageal adenocarcinoma. Treatment begins with lifestyle modification and medical therapy. If these fail, surgical and endoscopic surgical techniques are available, to provide treatment, symptom relief, and reduce long-term PPI use.

Proton-pump inhibitor use amongst patients with severe hypomagnesemia.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.

Investigation of Enterogermina's Protective and Restorative Mechanisms on the Gut Microbiota with PPI, Using SHIME Technology.

Proton pump inhibitors (PPIs) are commonly prescribed medications associated with changes in the gut microbiome and dysbiosis when used long-term. Probiotics, such as Enterogermina® (containing four strains of Bacillus clausii) reduce side effects from triple therapy with PPI+antibiotics. We aim to assess the ability of this probiotic in preventing and/or treating the dysbiosis induced by PPI use. Faecal samples from six healthy donors were used to colonise a Triple-Mucosal-Simulator of the Human Intestinal Microbial Ecosystem® model with added ileal compartment. Changes in the microbial community composition and metabolite production were measured for PPI alone (control), PPI+Enterogermina (preventative), and Enterogermina treatment after PPI (curative). Differences were assessed by one-way ANOVA with Tukey's multiple comparisons test. The model was shown to replicate some of the effects of long-term PPI use. There were significant changes in microbial diversity and an increase in butyrate levels in the preventative and curative arms, indicative of a beneficial effect to gut health. Probiotic use countered some of the effects of PPI use: Streptococcus bovis levels increased in the control arm but reduced following probiotic treatment. These results show that probiotic treatment with B. clausii may have beneficial effects on the gut microbiota following PPI treatment.

Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers.

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.

Proton Pump Inhibitor Use and Risk of Dementia in Older Adults: A Systematic Review

Proton pump inhibitors (PPIs) are commonly used for gastroesophageal reflux disease. Previous studies have raised concerns about the impact of PPIs on cognition in older adults, but the evidence supporting this concern is lacking. This article aims to analyse the available data regarding the impact of long-term PPI use on cognition in older adults. We searched PubMed for relevant studies conducted between 2015 and 2022. Seventeen such studies were identified. Limitations to available research data include the fact that studies are mainly observational, use heterogeneous study methods and do not account for confounding variables such as B12 deficiency, Helicobacter pylori infection, and thyroid dysfunction. Overall, this search did not find a compelling association between PPI use and cognitive decline.

Current management of gastro-oesophageal reflux disease-treatment costs, safety profile, and effectiveness: a narrative review.

The purpose of this study was to review the current management of gastro-oesophageal reflux disease (GORD), including treatment costs, safety profile and effectiveness. A literature review was performed of randomized-controlled trials, systematic reviews, Cochrane reports and National/Societal guidelines of the medical, endoscopic and surgical management of GORD. Proton pump inhibitor (PPI) prescribing patterns and expenditure were reviewed in different countries, including Australia, Canada, New Zealand, UK and USA. Proton pump inhibitors (PPIs) are primarily indicated for control of GORD, Helicobacter pylori eradication (combined with antibiotics), preventing NSAID-induced gastrointestinal bleeding and treating peptic ulcer disease. There is widespread overprescribing of PPIs in Western and Eastern nations in terms of indication and duration, with substantial expense for national health providers. Despite a favourable short-term safety profile, there are observational associations of adverse effects with long-term PPIs. These include nutrient malabsorption, enteric infections and cardiovascular events. The prevalence of PPI use makes their long-term safety profile clinically relevant. Cost-benefit, symptom control and quality-of-life outcomes favour laparoscopic fundoplication rather than chronic PPI treatment. Laparoscopic fundoplication in long-term management of PPI-responsive GORD is supported by SAGES, NICE and ACG, and PPI-refractory GORD by AGA and SAGES guidelines. The importance of establishing a definitive diagnosis prior to invasive management is emphasized, especially in PPI-refractory heartburn. We examined evidence-based guidelines for PPI prescribing and deprescribing in primary care and hospital settings and the need for PPI stewardship and education of health professionals. This narrative review presents the advantages and disadvantages of surgical, endoscopic and medical management of GORD, which may assist in shared decision making and treatment choice in individual patients.This paper was presented (GS020) at the 88th RACS Annual Scientific Conference, 6-10 May, 2019.

Use of proton pump inhibitor may be associated with progression of cerebral small vessel disease.

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. However, recent studies have shown that chronic PPI use is associated with the progression of endothelial senescence and cerebrovascular diseases. We hypothesized that PPI users might be vulnerable to fast progression of cerebral small vessel disease (SVD) with cumulative effects. Four hundred and eleven patients, who underwent brain magnetic resonance imaging, more than twice between January 2010 and December 2016 were screened. Patients aged < 50 years, and those who had concomitant diseases that might affect the progression of cerebral SVD were excluded. Baseline characteristics were collected. We evaluated the severity of SVD using the Fazekas score, the number of cerebral microbleeds (CMBs), and assessed the progression of SVD or CMBs based on the cumulative dose of PPIs. Among the included patients (N = 137), 39 were PPI ever-users. Univariate Cox regression analysis showed that PPI use was independently associated with the progression of Fazekas score only in the deep white matter hyperintensities (WMH) (hazard ratio [HR] 2.891, 95% confidence interval [CI] 1.210-6.906, P = 0.017). In multivariate Cox regression analysis, long-term PPI use was associated with a progression of Fazekas score in the deep WMH (HR 3.453, 95% CI 1.027-9.475, P = 0.045). However, PPI use was not associated with the progression of CMB. The present study results suggest that long-term use of PPIs is associated with the progression of deep cerebral WMH. Further research is needed using a large number of patients to validate this relationship.

Effect of proton pump inhibitors in infants with esophageal atresia on the gut microbiome: a pilot cohort

BackgroundThe effects of proton-pump inhibitors (PPIs) on the infant microbiome remain unclear. Swedish pilot cohort study to assess the longitudinal effect of long-term PPI on the infant gut microbiome, including ten newborn infants operated for esophageal atresia exposed to PPIs (mean 57 weeks), compared to healthy one-year-old controls. All children were born vaginally and were otherwise healthy. Within- and between sample diversity of the fecal microbiome was assessed using untargeted whole genome Shotgun metagenomics which sequences all the DNA in the sample and can capture genes rather than a taxonomic fingerprint.ResultsA longer duration of PPI-use was associated with considerable changes in evenness and high variation on diversity within samples compared to a shorter duration of use. The limited difference between baseline samples and controls suggests that this shift was most likely due to the drug exposure and not the underlying alterations on the microbiome. We found no associations with the number of antibiotic treatment episodes among the PPI-users.ConclusionProlonged PPI-use may alter the early infant gut microbiome composition, especially those with the most prolonged duration of use.

Monitoring of serum magnesium levels during long-term use of proton pump inhibitors in elderly japanese patients: is it really necessary or not?

BackgroundLong-term use of proton pump inhibitors (PPIs) has been found to significantly lower serum magnesium levels in patients in the USA and Europe. The package inserts of PPIs in these countries clearly state that healthcare professionals should consider monitoring magnesium levels prior to initiation of PPI treatment and periodically thereafter. However, the package inserts of PPIs in Japan do not clearly mention the monitoring of magnesium levels. In this study, we evaluated the relationship between long-term use of PPIs and the lower serum magnesium concentrations in elderly Japanese patients.MethodsUsing a retrospective observational approach, a total of 264 Japanese outpatients were included in the study. Patients over the age of 75 years were considered elderly. Serum magnesium levels of the patients were measured in units of 0.1 mg/dL between January 2016 and June 2022 at the Higo Internal Medicine Clinic and Ai Pharmacy in Kyoto, Japan.ResultsFour of the 264 eligible patients were diagnosed with hypomagnesemia. Three were PPI non-users, and one was a PPI user. Serum magnesium concentrations were significantly lower in PPI users (n = 47) than in non-users (n = 85; 2.1 ± 0.2 vs. 2.2 ± 0.3 mg/dL, p < 0.05) in the 132 elderly patients. Comorbidity included diabetes mellitus in both PPI users (23.4%) and non-users (57.6%) and hyperlipidemia in both PPI users (61.7%) and non-users (41.2%).ConclusionPPIs are commonly used oral drugs for elderly patients. There was an association between the long-term use of PPIs and lower serum magnesium concentrations in elderly patients. Although the difference in the decrease in serum magnesium concentrations was within the normal range of serum magnesium levels, health care professionals should consider monitoring serum magnesium levels periodically in elderly patients receiving long-term PPIs.

Association between Proton Pump Inhibitor Use and the Risk of Female Cancers: A Nested Case-Control Study of 23 Million Individuals.

Firm conclusions about whether long-term proton pump inhibitor (PPI) drug use impacts female cancer risk remain controversial. We aimed to investigate the associations between PPI use and female cancer risks. A nationwide population-based, nested case-control study was conducted within Taiwan's Health and Welfare Data Science Center's databases (2000-2016) and linked to pathologically confirmed cancer data from the Taiwan Cancer Registry (1979-2016). Individuals without any cancer diagnosis during the 17 years of the study served as controls. Case and control patients were matched 1:4 based on age, gender, and visit date. Conditional logistic regression with 95% confidence intervals (CIs) was applied to investigate the association between PPI exposure and female cancer risks by adjusting for potential confounders such as the Charlson comorbidity index and medication usage (metformin, aspirin, and statins). A total of 233,173 female cancer cases were identified, consisting of 135,437 diagnosed with breast cancer, 64,382 with cervical cancer, 19,580 with endometrial cancer, and 13,774 with ovarian cancer. After matching each case with four controls, we included 932,692 control female patients. The number of controls for patients with breast cancer, cervical cancer, endometrial cancer, and ovarian cancer was 541,748, 257,528, 78,320, and 55,096, respectively. The use of PPIs was significantly associated with reduced risk of breast cancer and ovarian cancer in groups aged 20-39 years (adjusted odds ratio (aOR): 0.69, 95%CI: 0.56-0.84; p &lt; 0.001 and aOR: 0.58, 95%CI: 0.34-0.99; p &lt; 0.05, respectively) and 40-64 years (aOR: 0.89, 95%CI: 0.86-0.94; p &lt; 0.0001 and aOR: 0.87, 95%CI: 0.75-0.99; p &lt; 0.05, respectively). PPI exposure was associated with a significant decrease in cervical and endometrial cancer risks in the group aged 40-64 years (with aOR: 0.79, 95%CI: 0.73-0.86; p &lt; 0.0001 and aOR: 0.72, 95%CI: 0.65-0.81; p &lt; 0.0001, respectively). In contrast, in elderly women, PPI use was found to be insignificantly associated with female cancers among users. Our findings, based on real-world big data, can depict a comprehensive overview of PPI usage and female cancer risk. Further clinical studies are needed to elucidate the effects of PPIs on female cancers.

Evaluation and management of gastroesophageal reflux disease: A brief look at the updated guidelines.

Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disorder seen in primary care offices and is usually managed with proton pump inhibitors (PPIs). The authors present an overview of the updated guidelines from the American College of Gastroenterology, which address the evaluation and management of GERD, including the consequences of long-term PPI therapy and emerging therapies.

Proton Pump Inhibitor Use and Cognitive Function in the Boston Puerto Rican Health Study.

There is a lack of consensus among studies on the association between proton pump inhibitor (PPI) use and cognitive impairment. This association is not well studied among minority populations, including among Puerto Ricans. Therefore, we sought to examine this association among Boston-area Puerto Ricans. The Boston Puerto Rican Health Study is an ongoing longitudinal cohort that enrolled 1499 Boston-area Puerto Rican adults, aged 45-75 years at baseline. Complete outcome and exposure data was available for 1290 baseline participants. Covariate-adjusted linear regression and linear mixed effects models were used to examine the association between PPI use, and global cognition, executive function, and memory cross-sectionally and longitudinally over ~12.7 years of follow-up. Furthermore, we examined the cross-sectional association between long-term PPI use (continuous use of ~6.2 years) and global cognition, executive function, and memory. Among 1 290 participants at baseline, 313 (24.3%) self-reported PPI use. Baseline PPI use was not associated with baseline global cognition, executive function, or memory. Baseline PPI use also did not alter the trajectory of global cognition, executive function, or memory over ~12.7 years of follow-up. Long-term PPI use was not associated with global cognition, executive function, or memory over ~12.7 years of follow-up. In this study of Boston-area Puerto Ricans, we did not observe an association between PPI use and global cognition, executive function, or memory either cross-sectionally or over 12.7 years of follow-up.

The Effects of Proton Pump Inhibitors in Acid Hypersecretion-Induced Vitamin B12 Deficiency: A Systematic Review (2022).

Gastroesophageal reflux disease (GERD) is the most common disease, for which proton pump inhibitors (PPIs) are a widely used class of drugs. Due to their efficacy and relative safety profile, PPIs are used chronically by GERD patients. Although it is a safe drug, particular attention focuses on the long-term adverse effects of PPI. The association with vitamin deficiencies has received additional focus since chronic PPI treatment increases the incidence of vitamin B12 deficiency, especially in the elderly. However, numerous studies regarding the establishment of an association between PPI and vitamin B12 status revealed conflicting results. In this systematic review, we systematically examined observational studies that focused on the impact of chronic PPI effects on vitamin B12 absorption and diagnostic biomarkers of vitamin B12 deficiency. Our review showed significant changes in diagnostic biomarkers of vitamin B12 status in long-term PPI users, including elevated homocysteine and methylmalonic acid (MMA) concentration levels defining cellular vitamin B12 deficiency. Although there is uncertainty regarding the exact mechanism, it supports the concept that long-term intake of PPI can have clinical implications for vitamins.

Incorporation of Student Pharmacists into a Proton Pump Inhibitor Deprescribing Telehealth Program for Rural Veterans.

Background: Proton pump inhibitors (PPIs) are among the most widely prescribed class of medications in the United States. Although effective in the treatment of acid related disease, inappropriate PPI use is prevalent, and long-term PPI use has been associated with adverse effects. Objectives: This evaluation explores the novelty of a student-pharmacist directed PPI deprescribing telehealth program with the goals of (1) determining whether PPIs are appropriately prescribed in Veterans via remote student-led chart reviews, (2) identifying if a gap exists between urban and rural Veterans prescribed a PPI, and (3) assessing the feasibility of integrating student pharmacists into the PPI deprescribing process utilizing telehealth visits through a pilot study. Methods: Student pharmacists evaluated PPI appropriateness in Veterans at the William S. Middleton Veterans Hospital. Students collected data via remote chart reviews, compared appropriateness of PPI therapy in rural versus urban Veterans, and conducted a deprescribing pilot call study in rural Veterans with inappropriate PPI indications. Clinical decision-making was agreed upon in collaboration with pharmacist preceptors, however all means of communication with Veterans was performed by student pharmacists. Results: 51% of Veterans were found to have an inappropriate indication for their PPI, though comparison of inappropriate PPI use in rural versus urban Veterans was not statistically significant (n=170, p-value 0.34). 83% of Veterans agreed to proceed with PPI deprescribing and 71% of Veterans ended the pilot study with at least some degree of PPI dose reduction (n=33). Conclusion: Inappropriate PPI use among rural and urban Veterans is prevalent, however a significant difference was not observed between the two cohorts. Student pharmacists are capable of successful telehealth deprescribing interventions in collaboration with pharmacists.

Metastatic multiple gastric neuroendocrine tumors with a long history of proton pump inhibitor use: A case report

It is widely accepted that gastric neuroendocrine tumors (NETs) develop due to enterochromaffin-like (ECL) cell proliferation following exposure to hypergastrinemia, which causes hyperplastic-dysplastic-neoplastic changes. Here we describe the case of a 46-year-old female patient diagnosed with metastatic NETs by liver biopsy and evaluated at an external center. At our hospital, nodular structures extending from the cardia to the antrum were observed by gastroscopy, considered the primary tumor focus. Histopathological examination revealed a trabecular-insular pattern, with microNETs consisting of monotone cells with round-oval nuclei and surrounding neuroendocrine cell hyperplasia foci and fundic gland polyps. The patient had a history of regular proton pump inhibitor (PPI) use for 10 years and a serum gastrin of 9240 pg/mL. A 3-cm metastatic lesion in the left lobe of the liver was observed in whole-body imaging with octreotide. By gastrectomy, we observed a large number of nodular lesions in the corpus-antrum and a 3-cm diameter lesion in the hepatectomy material. Histopathological examination revealed NETs in multiple foci with submucosal invasion in the stomach. The Ki-67 proliferative index was 3%. Metastatic tumors of similar morphology were found in the liver and three of the greater curvature lymph nodes. We made a diagnosis of multiple gastric NETs (Grade 2). In Type I gastric NETs, the neuroendocrine cell proliferation spectrum up to NET is observed as a result of hypergastrinemia due to atrophic gastritis. Also, in experimental studies, prolonged hypergastrinemia has been reported to cause ECL cell neoplasms in animals treated with PPIs. Although our case could be accepted as Type 1 NET, the possibility of developing NET secondary to long-term PPI use should also be considered.

Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy

BackgroundThere is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC.MethodsThis population-based cohort study included all long-term users of PPI therapy in Sweden in 2005–2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression.ResultsAmong 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67–0.98) and OAC (IRR 0.80, 95% CI 0.68–0.96), but not OSCC (IRR 1.10, 95% CI 0.82–1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy.ConclusionDiscontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use.

S442 Utilization of Diagnostic Testing and Indications for Long-Term Twice-Daily Proton Pump Inhibitor (PPI) Therapy for Gastroesophageal Reflux Disease (GERD) in a Large Healthcare System

Introduction: For symptoms potentially associated with GERD, guidance recommends de-prescribing long-term PPI therapy based on symptoms if possible, particularly in the absence of objective diagnostic findings. We assessed the utilization and yield of diagnostic evaluation (upper endoscopy (EGD) and/or reflux monitoring) among patients with GERD diagnoses receiving long-term twice-daily PPI therapy. Methods: From a healthcare system database, adults with GERD diagnoses (per ICD coding) who received prescriptions for twice-daily PPI for at least 90 days from 2018-2021 were identified. CPT analyses were performed to identify the proportions who underwent EGD and reflux monitoring. Characteristics of patients who underwent diagnostic testing were compared to those who did not. Further, those with objective EGD findings potentially warranting long-term PPI (such as erosive or eosinophilic esophagitis, peptic stricture, Barrett’s esophagus, ulcer) were compared to those without such findings on EGD. Factors significant on univariate analysis were included in multivariate models to identify predictors of A) undergoing diagnostic evaluation, and B) having positive EGD findings. Results: 5565 patients (57.7±0.2 yrs; 67.4% female; BMI 31.3±0.1) met inclusion criteria. 2696 (47.7%) had upper endoscopy, 491 (8.7%) had reflux monitoring, and 2735 (48.4%) had either upper endoscopy or reflux monitoring performed. Factors associated with diagnostic testing included younger age, female gender, and non-white race (Table, Figure A). Among those who underwent EGD, 42.2% had endoscopic findings potentially warranting long-term PPI (37.7% for females vs 52.2% for males; 34.7% for non-white patients vs 47.3% for white patients). Factors associated with the presence of EGD findings included older age, male gender, and white race (Figure B). Conclusion: Among patients receiving prescriptions for long-term, twice-daily PPI for GERD diagnoses, over half did not have procedural diagnostic evaluation documented per CPT analysis, suggesting providers may rely on patient symptom reporting to guide long-term PPI prescriptions. Of those with documented EGD, less than half had objective findings to potentially corroborate the need for long-term, twice-daily PPI. These findings warrant further investigation into potential disparities in care around long-term PPI prescribing patterns based on symptoms and symptom response versus diagnostic evidence.Figure 1.: Forest Plots for Multivariate Analysis of Factors Associated with A) Diagnostic Evaluation (Upper Endoscopy and/or Ambulatory Reflux Monitoring) among Patients with GERD Diagnoses Prescribed Twice-Daily Long-Term PPI Therapy; and B) Objective Endoscopic Findings Potentially Warranting Twice-Daily Long-Term PPI Therapy. Odds Ratios are Depicted with Bars Representing Associated 95% Confidence Intervals; Values Not Crossing the Dashed Line at 1 are Significant. Odds ratios for smoking status variables are in reference to no smoking history. Table 1. - Comparisons Between Patients who Underwent Diagnostic Evaluation (with Upper Endoscopy and/or Ambulatory Reflux Monitoring) and Those Patients Who did Not Undergo Diagnostic Evaluation Evaluated (n=2735) Not Evaluated (n=2920) p Values Age (years) 57.1±0.3 58.3±0.3 0.005* Body Mass Index 31.0±0.1 31.6±0.2 0.006* Gender (female) 1898 (69.4%) 1916 (65.6%) 0.002* Race (data missing = 97) White 1681 (62.4%) 1998 (69.8%) < 0.001* Black 838 (31.1%) 672 (23.5%) Asian 62 (2.3%) 77 (2.7%) Other 115 (4.3%) 115 (4.0%) Ethnicity (data missing =109) Non-Hispanic 2505 (93.1%) 2663 (93.3%) 0.71 Hispanic or Latino 187 (7.0%) 191 (6.7%) Married (data missing =58) Married 1526 (56.2%) 1658 (57.5%) 0.32 Not Married 1189 (43.8%) 1224 (42.5%) Smoking Status (data missing = 5) Current 279 (10.2%) 390 (13.4%) < 0.001* Former 974 (35.6%) 945 (32.4%) Never 1481 (54.2%) 1581 (54.2%)

Potential Risks and Drawbacks of Long-Term Proton Pump Inhibitors Use

In today's world, proton pump inhibitors (PPIs) are one of the most commonly prescribed pharmacological types. Many gastrointestinal diseases such as gastroesophageal reflux or Barrett's esophagus, as well as laryngopharyngeal reflux, may benefit from these. However, numerous studies have been published that link PPIs to a variety of dangers and problems, including bone fractures, infection, myocardial infarction, renal illness, and dementia. By examining key articles and addressing the debates around those findings, this review exposes several of these potential negative side effects. To provide proper counseling of their patients, the diligent otolaryngologist should be aware of the current status of the literature and the hazards associated with prescribing PPIs. PPIs must be prescribed correctly in order to optimize outcomes and reduce risks and costs to the healthcare system. Overuse and misuse of PPIs, on the other hand, raises the risk of side effects. Because most gastric-acid-related illnesses necessitate long-term treatment, patients taking additional drugs in addition to a PPI are likely to experience clinically significant adverse drug interactions. Clinicians must only administer PPIs when they are proved to be required.

Proton Pump Inhibitors and Bone Health: An Update Narrative Review.

Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.