Chronic Proton Pump Inhibitors Research Articles

How Did Consultants and Trainees Respond to a Survey About Proton Pump Inhibitors in a Tertiary Academic Center?

Introduction: Proton pump inhibitors (PPI) are ubiquitous in the field of gastroenterology. Recent publications suggest possible links between chronic PPI use and several adverse events. As a result, more patients are asking questions about risk of PPI use, and providers face challenges regarding their appropriate use and their safety. We aimed to examine providers' knowledge and attitudes toward reported adverse effects of PPI and compare consultants and trainees' prescription practices. Methods: A detailed non-incentivized online survey was sent to medical providers; trainees (residents and fellows) and consultants across seven specialties at a tertiary academic center. The survey included 21 questions exploring providers' actions in response to challenging clinical scenarios dealing with PPI use. Chi-square was used to compare responses from trainees and consultants. Results: We sent the survey to 199 providers at our center. 71 providers (27 trainees and 44 consultants) completed the survey (35.7 % response rate). Trainees were residents from internal medicine, fellows were from gastroenterology, cardiology, hematology/ oncology, pulmonary and nephrology. Consultants were providers from cardiology, pulmonary medicine, endocrinology, family medicine, general internal medicine, hematology/oncology, and nephrology. More consultants than trainees cited that these reports changed their practice (81.8% vs 59.2%, p=0.03). Table (1) shows consultants and trainees actions when facing challenging patients using PPI. When asked about using PPI in patients with coronary artery disease who require clopidogrel, more trainees than consultants (59.3% vs 41.8%) chose to continue omeprazole. Both groups (trainees and consultants) agreed to monitor renal function in patients taking PPI who are at higher risk to develop chronic kidney disease (83.7% vs 92.6%). Figure (1) shows concerning side effects of PPI reported by providers. All p-values are not statistically significant. Most providers (consultants and trainees) conformed that scholastic sessions (e.g. grand rounds), would be useful to help address these challenges (90.9% vs 88.9%). Conclusion: Provider education about the adverse events that might be linked to PPIs is critical. More trainees switched their patients from PPI to other medications. In a similar fashion, both consultants and trainees were concerned about clostridium difficile infection and kidney disease.Table 1: Providers' responses when facing challenges regarding PPI side effectsFigure 1

Do Recent Reports About the Adverse Effects of Proton Pump Inhibitors Change Providersʼ Prescription Practice?

Introduction: Proton pump inhibitors (PPI) are indicated to treat gastroesophageal reflux disease, peptic ulcer disease, dyspepsia and to prevent GI bleeding. Studies have shown increasing inappropriate PPI use. Recent reports in the press and social media have highlighted new data suggesting a possible link between chronic PPI use and several medical problems, leading to frequent patient inquiries about these associations. Providers face the challenges of balancing PPI benefits and risks. We aimed to explore providers' knowledge and attitudes toward reported adverse effects of PPI and compare gastrointestinal (GI) and Non-GI providers' prescription practices.Table 1: Concerning side effects PPI to the patients reported by providersTable 2: Concerning side effects of PPI to providersFigure 1Methods: A comprehensive non-incentivized electronic survey was sent to all providers (residents, fellows, advanced practice providers and consultants across seven specialties) at a tertiary academic center. The survey contained 21 questions covering the following provider aspects: (1) demographics (2) responses to challenging clinical scenarios dealing with PPI use. Chi-square was used to compare responses from GI providers to those from non-GI providers. Results: We sent the survey to 254 providers at our center. 88 providers (22 GI and 66 non-GI) completed the survey (34.6 % response rate). Non-GI providers included cardiology, pulmonary medicine, endocrinology, family medicine, general internal medicine, hematology/oncology, and nephrology. More GI providers reported that these potential side effects changed their practice (63.6% in GI vs 48.5 in non-GI, p-value 0.4). A larger percentage of GI providers lowered the dose of PPI (18.2 % vs 1.5% p-value 0.003). Table (1) shows what providers do when facing challenging patients on PPI therapy. When asked which side effects are more concerning to patients, GI providers were more likely to cite osteoporosis or fractures than non-GI providers (40.9% vs 15.1% p-value 0.01) and dementia (31.8% vs 25.8 p-value 0.58). Table (2) and (3) show concerning side effects per patients and providers, respectively. Most providers (GI and non-GI) agreed that educational activities (e.g. grand rounds), would be helpful to address these challenges (95.5% vs 89.4%, p-value 0.67). Conclusion: Educating patients and providers about potential side effects of PPI is imperative. More GI providers reduced the dose of PPI for their patients while more non-GI providers switched to another medication (e.g. H2 blockers) or referred to GI clinic. Educational activities might be helpful in addressing these challenges.

A Wolf in Sheepʼs Clothing: A Unique Case of Zollinger-Ellison Syndrome Masquerading as Ileal Crohnʼs Disease

Zollinger-Ellison Syndrome (ZES) often presents with peptic ulcer disease, symptoms of gastroesophageal reflux disease (GERD) and chronic diarrhea. This is the result of gastric acid hypersecretion secondary to ectopic gastrin production, typically, from a pancreatic or duodenal neuroendocrine tumour (NET). This report presents a unique case of a patient initially thought to have small bowel Crohn's disease (CD). Incidental discovery of a gastrinoma led to a diagnosis of ZES. A 57 year old male was referred to an outside gastroenterology clinic for evaluation and management of a longstanding history of dyspeptic symptoms and diarrhea. On review of his history, he had a repair of a perforated jejunal ulcer 3 years prior, presumed to have been related to intermittent use of non-steroidal anti-inflammatory drugs. He remained on chronic proton-pump inhibitor therapy, with adequate control of his dyspepsia. As part of his work-up for chronic diarrhea, he underwent upper endoscopy and colonoscopy. The upper tract was grossly normal, and biopsies showed mild chronic gastritis. Colonoscopy showed a grossly and histologically normal colon, but the terminal ileum could not be intubated. Subsequent CT enterography showed 2 fibrotic strictures of the distal ileum, leading to a diagnosis of Crohn's disease, and prompting referral to our Inflammatory Bowel Diseases Clinic. Incidental note was made of a 5cm mass at the tail of the pancreas, consistent with a probable NET, prompting immediate surgical referral. By the time of his presentation to our clinic, he was 2 months post the resection of his tumour, which was proven histologically to be a gastrin-producing NET. He reported complete resolution of his chronic diarrhea and dyspepsia. A diagnosis of ZES was entertained and a work-up for MEN-1 was initiated. Brain MRI demonstrated a 2 mm pituitary microadenoma, consistent with possible MEN-1. In the literature, 75% of gastrointestinal ulceration in ZES occur in the first portion of the duodenum with ulcers less likely in the distal duodenum and jejunum. There are no reports of ZES associated ulceration occurring in the ileum. This patient's ileal strictures are hypothesized to be secondary to ulcers due to the gastrinoma. This would offer a unifying diagnosis for this patient's findings and would explain the resolution of his symptoms with resection of his tumour.

Impact of proton pump inhibitor treatment on pancreatic beta-cell area and beta-cell proliferation in humans.

Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined. The group was subdivided into patients without diabetes (n = 27), pre-diabetic patients (n = 31) and patients with diabetes (n = 35). Fasting glucose and HbA1c levels were not different between patients with and without PPI therapy (P = 0.34 and P = 0.30 respectively). Beta-cell area was higher in patients without diabetes than in patients with pre-diabetes or diabetes (1.33 ± 0.12%, 1.05 ± 0.09% and 0.66 ± 0.07% respectively; P < 0.0001). There was no difference in beta-cell area between patients with and without PPI treatment (1.05 ± 0.08% vs 0.87 ± 0.08%, respectively; P = 0.16). Beta-cell replication was rare and not different between patients with and without PPI therapy (P = 0.20). PPI treatment was not associated with increased duct-cell replication (P = 0.18), insulin expression in ducts (P = 0.28) or beta-cell size (P = 0.63). These results suggest that in adult humans, chronic PPI treatment does not enhance beta-cell mass or beta-cell function to a relevant extent.

Potential adverse effects of long term use of Proton Pump Inhibitors

Proton-Pump Inhibitors (PPIs) have changed the therapy of numerous upper gastrointestinal tract disorders; but their use is not without risk of adverse effects. Recent studies suggest more serious adverse events with chronic use of PPIs. Because of these risks, clinicians should reassess individual patient’s needs for chronic PPI therapy.

Effect of the Prophylactic Use of Proton-Pump Inhibitors on the Pattern of Gastrointestinal Symptoms in Patients Late After Kidney Transplant.

Although immunosuppressive drugs have been recognized as leading causes of gastrointestinal symptoms after kidney transplant, other widely used medications such as proton-pump inhibitors recently have been implicated. Our aim was to study the effects of chronic proton-pump inhibitor therapy on gastrointestinal symptoms in clinically stable patients late after kidney transplant. The study comprised 100 kidney transplant recipients (66 men and 34 women, mean age of 49 ± 12 y, mean time after transplant of 56 ± 46 mo). All patients completed the Gastrointestinal Symptoms Rating Scale and the Quality of Life Questionnaire SF-8 surveys. The most commonly reported symptoms included borborygmus (27%), flatulence (23%), abdominal distension (18%), urgent need of defecation (17%), and heartburn, acid reflux, and eructation (13%). Proton-pump inhibitors were chronically used by 50% of patients and sporadically by 33%. Gastrointestinal Symptoms Rating Scale scores were higher in patients who used proton-pump inhibitors (mean score of 7.8 ± 5.5 vs 4.6 ± 3.0; P = .013). Total score of items representing diarrhea in the Gastrointestinal Symptoms Rating Scale (increased passage of stools, loose stools, urgent need of defecation, incomplete evacuation) was higher in patients treated with proton-pump inhibitors than in those not treated (2.3 ± 2.2 vs 1.3 ± 1.9; P = .04). Chronic use of proton-pump inhibitors may increase the prevalence of gastrointestinal symptoms, particularly diarrhea, in patients late after kidney transplant.

Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia.

A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.

BackgroundChronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats.ObjectivesProlonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats.AnimalsSix healthy adult DSH cats.MethodsIn a within subjects, before and after design, cats received placebo followed by omeprazole (0.83–1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two‐way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole.ResultsNo significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole.Conclusions and Clinical ImportanceAlthough further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats.

Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study.

BackgroundMiddle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs.MethodsIn this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use.ResultsIn patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545).ConclusionsOne-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs, thienopyridines, anticoagulants, and PPIs increased the risk of acute small intestinal bleeding. However, there were no significant interactions found between antithrombotic drugs and PPI use for bleeding risk.

Deprescribing in a family health team: a study of chronic proton pump inhibitor use.

BACKGROUND Proton pump inhibitors (PPIs) are often used inappropriately, without an indication, or for longer durations than recommended. Few tools exist to guide reassessment of their continued use and deprescribing if required. We aimed to reduce inappropriate drug use by developing and implementing a PPI deprescribing tool and process in a family medicine unit. ASSESSMENT OF PROBLEM Primary care providers of adults taking a PPI for 8 weeks with an upcoming periodic health examination were reminded to reassess therapy via electronic medical record (EMR) messaging. A PPI Deprescribing Tool was uploaded into the EMR as a second reminder and to guide reassessment and deprescribing where indicated. Ten weeks after the examination a chart review assessed changes to PPI use. A follow up survey of providers assessed the utility and barriers to implementing the Deprescribing Tool. RESULTS Forty-three of 46 patients on PPIs (93%) had their PPI reassessed, resulting in 11 patients (26%) having their PPI deprescribed. Strategies for Improvement Routine reassessment of long-term medications is often overlooked because of extensive demands on primary care providers' time. Deprescribing likely improved because potentially eligible patients were identified to the provider and a tool was provided at the time of the encounter to guide the deprescribing process. LESSONS Reassessment and deprescribing of PPIs can be supported by implementing a standardised process and use of guidance tools for clinicians. Providers found the timely and selective reminder message to deprescribe the most useful component of the intervention. KEYWORDS proton pump inhibitor; deprescribing; reassessment; primary care; medication therapy management; gastroesophageal reflux disease.

Magnesium Deficiency and Proton-Pump Inhibitor Use: A Clinical Review.

The association of proton-pump inhibitor (PPI) use and hypomagnesemia has garnered much attention over the last 5 years. A large body of observational data has linked chronic PPI use with hypomagnesemia, presumably due to decreased intestinal absorption and consequent magnesium deficiency. However, despite the increasing prevalence of this highly popular class of medicine, and despite potential significant risks associated with magnesium depletion, including cardiac arrhythmias and seizures, there are no well-designed studies to delineate the nature of this observed association. Consequently, providers must use best judgment to inform clinical decision making. This review summarizes the current body of evidence linking PPI use with hypomagnesemia, acknowledges the possibility of significant residual confounding in the observational data, explains potential physiologic mechanisms, and offers clinical recommendations.

Low Prevalence of Hypomagnesemia in Long-term Recipients of Proton Pump Inhibitors in a Managed Care Cohort.

Chronic intake of proton pump inhibitors (PPI) has been associated with hypomagnesemia, but prevalence of PPI-associated hypomagnesemia is not known. We examined the prevalence of hypomagnesemia among long-term PPI recipients by using a large health maintenance organization database. We collected data on 10,167 participants eligible for chronic drug prescriptions from 2008 through 2013. Adult subjects receiving continuous PPI therapy for ≥ 6 months between 2008 and 2013 and ≥ 1 serum magnesium determination(s) were identified. Patients with any magnesium levels less than 1.6 mg/dL were selected for analysis; those with recognizable causes of altered magnesium homeostasis were excluded. Five hundred ninety participants received long-term PPIs, and 414 (70.2%) met the inclusion criteria for a total exposure of 2293 PPI-years (average, 5.7 years/subject). Of these patients, 57 (13.8%) had ≥ 1 low serum magnesium; 5 were no longer on PPIs, and 44 had other recognizable causes for hypomagnesemia (25 receiving diuretics, 8 with chronic diarrhea, 8 with chronic kidney disease, and 3 with malignancies). Of the 8 remaining patients (7 female; mean age, 71.2 ± 13.4 years; mean daily medications, 5.4 ± 1.1), mild hypomagnesemia (range, 1.2-1.5 mg/dL) was noted in 13.9% of 289 measurements. All 8 patients had normal serum levels of magnesium at their final measurement. In the absence of known precipitating factors, chronic PPI use does not appear to be associated with hypomagnesemia.

Effect of Chronic Proton Pump Inhibitor Use on Serum Magnesium Levels in Pediatric Patients

Effect of Chronic Proton Pump Inhibitor Use on Serum Magnesium Levels in Pediatric Patients

Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD.

Until recently only two therapeutic options have been available to control symptoms and the esophagitis in chronic gastro-oesophageal reflux disease (GERD), i.e. lifelong proton pump inhibitor (PPI) therapy or anti-reflux surgery. Lately, transoral incisionless fundoplication (TIF) has been developed and found to offer a therapeutic alternative for these patients. To perform a double-blind sham-controlled study in GERD patients who were chronic PPI users. We studied patients with objectively confirmed GERD and persistent moderate to severe GERD symptoms without PPI therapy. Of 121 patients screened, we finally randomised 44 patients with 22 patients in each group. Those allocated to TIF had the TIF2 procedure completed during general anaesthesia by the EsophyX device with SerosaFuse fasteners. The sham procedure consisted of upper GI endoscopy under general anaesthesia. Neither the patient nor the assessor was aware of the patients' group affiliation. The primary effectiveness endpoint was the proportion of patients in clinical remission after 6-month follow-up. Secondary outcomes were: PPI consumption, oesophageal acid exposure, reduction in Quality of Life in Reflux and Dyspepsia and Gastrointestinal Symptom Rating Scale scores and healing of reflux esophagitis. The time (average days) in remission offered by the TIF2 procedure (197) was significantly longer compared to those submitted to the sham intervention (107), P<0.001. After 6months 13/22 (59%) of the chronic GERD patients remained in clinical remission after the active intervention. Likewise, the secondary outcome measures were all in favour of the TIF2 procedure. No safety issues were raised. Transoral incisionless fundoplication (TIF2) is effective in chronic PPI-dependent GERD patients when followed up for 6 months. Clinicaltrials.gov: CT01110811.

Factors Influencing Risk for Developing Pneumonia Amongst Proton Pump Inhibitor (PPI) Users

Introduction: Proton Pump inhibitors (PPIs) are widely used medication for variety of indications and generally well tolerated. Several studies have revealed the increased risk of pneumonia in patients taking PPIs. The goal of our study is to evaluate risk factors in PPI users, which can contribute to the acquisition of pneumonia. Methods: Our case-control study included 408 patients who were admitted to SUNY Upstate University hospital between Jan 2011 and Dec 2012. The cases had a primary diagnosis of community acquired pneumonia (CAP) or healthcare associated pneumonia (HCAP) with chest x-ray evidence of pneumonia and the controls had a primary diagnosis of chest pain without clinical or radiological evidence of pneumonia. The cases and the controls included subgroups of patients who used PPI vs. those who did not. Patients aged 18 years and above were enrolled. Data collection was performed using electronic medical records. Statistical analysis was performed using MS Excel and SPSS V.17 including descriptive statistics. Results: A total of 408 patients (cases 166 and 242 controls) were enrolled in the study. Out of all patients on PPI, 45% patients were started on PPI for stress ulcer prophylaxis. There was no difference between M: F ratio or average age between 2 groups. We found that PPI users have higher risk of acquiring pneumonia (OD - 1.5, P - 0.03). Smokers have higher risk of pneumonia while on PPI as oppose to those not on PPI (OR - 2.62, P - 0.009). Patients with GERD have higher risk of pneumonia while on PPI (OR - 1.80, P - 0.03). Patients with cancer who are on chemotherapy have higher risk of pneumonia while on PPI as compared to those who are not on PPI (OR - 4.2, OR - 0.0001). Use of statin reduces risk of pneumonia among PPI users (OR - 0.46, P - 0.01). History of Diabetes, heart failure, stroke, cirrhosis, Use of ACE inhibitors or systemic steroids did not influence risk of acquiring pneumonia while on PPI. Conclusion: We conclude that use of PPI does increase the risk of acquiring pneumonia. The factors leading to this enhanced risk are smoking, diagnosis of GERD, cancer patients on chemotherapy. Use of statin decreases risk of pneumonia. Re-evaluating need for chronic PPI especially in high risk group patients can help to avoid overuse and possibly decreasing risk of pneumonia in this patient population.

Consequences and Complications of Long Term Use of proton Pump Inhibitors

Proton Pump Inhibitors (PPIs) have become one of the most commonly prescribed category of drugs in both primary as well as tertiary care, commonly for gastric acid-related disorders. It is advised that no more than three 14-day treatment courses with PPIs should be used in one year. The two main indications for the long-term use of PPIs are gastro esophageal reflux disease and concomitant use with the maintenance dose of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). PPIs block the gastric H + ,K + -ATPase, inhibiting gastric acid secretion. If the drug is discontinued, there is a potential risk for rebound hypersecretion, creating a sort of dependency on the drug because the body is acclimated to having acid suppressed. The potential adverse effects relating to PPIs are Hypochlorhydria (11%- 24%) leading to pernicious anaemia and bone fractures(elevated risk after 7 years of continuous PPI therapy) and Hypergastrinemia (20%- 25%). Review of various literatures have shown that long-term PPI use is associated with upto fourfold increase in the risk of fundic gland polyps(upto 36%). Other potential consequences of chronic PPI use are malabsorption of key minerals (calcium and magnesium) in the body, increased risk of infections, cancer (5%-12%), severe drug interactions and birth defects. The most commonly seen infections with chronic PPI use are Enteric Infections and Community Acquired Pneumonia(CAP).A case-controlled study discovered an associated 2.5-fold risk of infection with concomitant PPI therapy. A population-based case-controlled study of7642 CAP cases identified, 11% were chronic PPI users. Another study found that 50% of chronic PPI users are more likely to develop CAP.Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from longterm therapy. In conclusion, based on the above evidences, pharmacists are poised to educate patients about the benefits and risks associated with chronic PPI use.

Long-Term Trends in Esophageal Candidiasis Prevalence and Associated Risk Factors with or without HIV Infection: Lessons from an Endoscopic Study of 80,219 Patients.

BackgroundThe prevalence of candida esophagitis (CE) might be changing in an era of highly active antiretroviral therapy (HAART) among HIV-infected patients or today’s rapidly aging society among non-HIV-infected patients. However, few studies have investigated long-term CE trends, and CE risk factors have not been studied in a large sample, case-control study. This study aimed to determine long-term trends in CE prevalence and associated risk factors for patients with or without HIV infection.MethodsTrends in CE prevalence were explored in a cohort of 80,219 patients who underwent endoscopy between 2002 and 2014. Risks for CE were examined among a subcohort of 6,011 patients. In risk analysis, we assessed lifestyles, infections, co-morbidities, immunosuppressants, and proton-pump inhibitors (PPIs). All patients were tested for HIV, hepatitis B or C virus, and syphilis infection. For HIV-infected patients, sexual behavior, CD4 cell count, history of HAART were also assessed.ResultsCE prevalence was 1.7% (1,375/80,219) in all patients, 9.8% (156/1,595) in HIV-infected patients, and 1.6% (1,219/78,624) in non-HIV-infected patients. CE prevalence from 2002-2003 to 2012-2014 tended to increase in non-HIV-infected patients (0.6% to 2.5%; P<0.01) and decrease in HIV-infected patients (13.6% to 9.0%; P=0.097). Multivariate analysis revealed increasing age (odds ratio [OR], 1.02; p=0.007), HIV infection (OR, 4.92; p<0.001), and corticosteroid use (OR, 5.90; p<0.001) were significantly associated with CE, and smoking (OR, 1.32; p=0.085) and acetaminophen use (OR, 1.70; p=0.097) were marginally associated. No significant association was found with alcohol consumption, hepatitis B or C virus, syphilis, diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic kidney disease, liver cirrhosis, anticancer, or PPIs use. In HIV-infected patients, CD4 cell count <100/μL (OR, 4.83; p<0.001) and prior HAART (OR, 0.35; p=0.006) were independently associated with CE, but sexual behavior was not. Among corticosteroid users, CE was significantly associated with higher prednisone-equivalent dose (p=0.043 for trend test).ConclusionsThis large, endoscopy-based study demonstrated that CE prevalence increased in non-HIV-infected patients but decreased in HIV-infected patients over 13 years. Risk analysis revealed that increasing age, HIV infection, and corticosteroids use, particularly at higher doses, were independently associated with CE, but alcohol, other infections, diabetes, anticancer drugs, and PPIs use were not.

Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes.

To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.

Mo1153 Gender Differences in Proton Pump Inhibitors (PPI) Dose Requirements for GERD: A Double-Blind Randomized Trial

Purpose: Current literature on the risk of fractures in patients on proton pump inhibitors (PPI) has yielded mixed results. This study evaluated the association between PPI use and incidence of osteoporotic fractures in male patients. Methods: Retrospective chart review was conducted at the Phoenix Veterans Affairs Health Care System from January 1, 1995 to July 23, 2012 for this case control study. Inclusion criteria included all male patients who were diagnosed as having a hip, wrist or spine fracture. A 3:1 sample of controls (patients without fractures) was drawn from the same period. Demographic information including age, body mass index (BMI), ethnicity, tobacco, and alcohol use were collected for all patients. Thiazides, bisphosphonates and steroid use data were also collected for patients with a fracture and PPI use. Results: A total of 246 male patients, mean age 65.3 years, suffered a hip (20%), wrist (30%) or spine (50%) fracture during the study period. Of these, 33 (13.4%) used chronic PPI's prior to the fracture. Among patients without fractures, 107 (14.1%) were using PPI's. Increasing BMI and PPI use are protective against hip fracture, (p<0.001). PPI's are protective against spine fracture and more so with increasing age, (p<0.05). For males not on PPI, incidence of spine fracture significantly increases with age. For those not taking bisphosphonate, taking PPIs reduces the risk of wrist fracture (p<0.001). Alcohol use was higher in the fracture group (74% vs 59%), and smoking rates were similar in both groups: 70% and 66% with and without fractures, respectively. Average BMI was 26 in both groups. Multivariable logistic regression modeling revealed a significant association of fracture with age and BMI, which depend on the fracture location. Conclusion: This study found no significant evidence of an association between chronic PPI use and hip, wrist or spine fracture in men over 55 years old. PPI use appears to be protective.

Therapy with proton pump inhibitors in patients with type 2 diabetes is independently associated with improved glycometabolic control.

Experimental data demonstrated that gastrin has incretin-like stimulating actions on β-cells, resulting in a promotion of glucose-induced insulin secretion. As proton pump inhibitors (PPIs) consistently increase plasma gastrin levels, a possible effect of this treatment on glucose-insulin homeostasis may be hypothesized. Therefore, the aim of this study was to evaluate the effect of chronic PPIs treatment on glycemic control in patients affected by type 2 diabetes. This is an observational, retrospective study. A total of 548 consecutive patients with type 2 diabetes (mean age ± SD: 67.1 ± 10.9 years, M/F: 309/239, diabetes duration: 12.4 ± 9.8 years) referring to our diabetes outpatient clinics were enrolled; among them, 45 %were treated with PPIs longer than 2 years for preventive/therapeutic purposes. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), serum lipids and transaminases were measured by standard laboratory methods. Major cardiovascular events and concomitant medications were recorded in all participants, and daily insulin requirement was calculated in insulin-treated subjects. PPIs-treated patients had significantly lower HbA1c (7.1 ± 1.07 %-54.1 ± 12 vs 7.4 ± 1.4 %-57.4 ± 8 mmol/mol, p = 0.011) and FPG (127 ± 36.9 vs 147.6 ± 49.4 mg/dl, p < 0.001) levels than those untreated. These differences increased in patients under insulin therapy and in those with concomitant PPIs + GLP-1-based therapy. The multivariate regression analysis demonstrated that the association between chronic PPIs treatment and HbA1c was independent from possible confounders (p = 0.01). PPIs treatment is associated with greater glycemic control in patients with type 2 diabetes, particularly in those on insulin- or GLP-1-based therapy. Our results suggest a role for PPIs in glucose-insulin homeostasis and may open a new scenario for diabetes therapy.