Proton Pump Inhibitor Failure Research Articles

The Effect of Proton Pump Inhibitors on Early Implant Failure A Retrospective Cohort Study

Background and Objectives: Maintenance of a firm and long-term stable osseointegration is the primary goal of implant dentistry. Time is used to define implant failure characteristics. Early implant failure (EIF) occurs up to one year after loading. Recent studies indicated an association between proton pump inhibitors (PPI) therapy and failure of osseointegration. The present study assessed whether the use of PPIs is a risk factor to EIF. Materials and methods: A retrospective cohort study including 687 patients and 2971 dental implants. The study group (PPIs users) comprised 17.3% (119) individuals and 18.7% (555) implants. The remaining cohort (82.7% (568) individuals and 81.3% (2416) implants) served as control. The information was taken from the patients' files. The following information was collected: age, gender, physical status, systemic diseases, HbA1C values before and after implant-supported prosthesis delivery in cases of diabetes mellitus, smoking, implant location, number of implants per individual, bone augmentation, implant brand, length and width, and EIF. EIF was defined as implant removal within a period of up to 12 months from loading. Results: EIF in PPIs vs. non-PPIs users was 19.3% vs. 14.3% (p = 0.16) at patient level and 5.4% vs. 3.5% at implant level (p = 0.03). Univariate analysis yielded factors significantly associated with PPIs use, including older age, physical status of the American Society of Anesthesiology (ASA) 3, hypertension, hyperlipidemia, diabetes mellitus, osteoporosis, cardiovascular accident (CVA), location (anterior mandible), shorter and narrower implants, and higher number of implants per individual. Multivariate analysis yielded statistically significant OR of 1.91; p = 0.01 for EIF following PPIs use and 2.3; p < 0.001 for location in anterior mandible. Conclusions: Patients and their healthcare providers are advised to carefully consider the potential risks of taking PPIs prior to dental implant surgery. Further research is needed to confirm these risks and elucidate systemic and local factors that may be involved in such outcomes.

Pharmacological Management of Gastro-Esophageal Reflux Disease: An Update of the State-of-the-Art.

Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic disorder, whose knowledge remains limited and the management of these patients changes continuously. This review provides a summary of the most recent advancements in the pathogenesis of this disease and the new drugs introduced into the market to overcome some of the unmet needs of traditional therapies. Nowadays, the most fruitful diagnostic examinations are 24-hour impedance-pH monitoring, which allows us to separate true NERD from esophageal functional disorders and high-resolution manometry, which helps to exclude the existence of motility disorders sharing the same symptoms of GERD. Proton pump inhibitors (PPIs) remain the first-choice therapy in the treatment of GERD, but a consistent proportion of these patients continue to experience symptoms despite their intake. These cases pertain mainly to the subpopulation with non-erosive reflux disease (NERD) and represent very challenging clinical situations, because it is mandatory to understand the reasons for PPI failure. The management of these difficult patients requires necessarily to test them and avoid the use of empiric treatments that are often unsuccessful, costly and potentially dangerous. Recently, several new drugs have been used to increase the defensive properties of this mucosa with promising results in randomized clinical trials.

Effect of Food and Dosing Regimen on Safety and Efficacy of Proton Pump Inhibitors Therapy—A Literature Review

Proton pump inhibitors (PPIs) are the first-choice drugs used to prevent and treat acid-related diseases. However, a lack of satisfactory response to the standard PPI dose (“PPI failure”) is often reported, especially in patients with gastroesophageal reflux disease. Poor compliance seems to be one of the main causes of PPI failure; hence, it is crucial to gain knowledge on how to properly administer PPIs. In this review, we aimed to evaluate the effect of food, beverages, and dosing regimen on pharmacokinetics and pharmacodynamics of PPIs and to frame recommendations for healthcare professionals to improve both patient’s counseling and compliance to treatment with PPIs. A total of 201 papers were identified following a literature search. After full-text evaluation, 64 studies were included in the review. Co-administration of PPIs with a meal may affect both their bioavailability and effectiveness; however, the influence of food depends on the type of drug and its formulation. Except for pantoprazole, PPIs can be administered in the morning or evening; however, morning intake generally provides better daytime control of gastric acidity. In most cases, the choice of the proper schedule of administration should be based on the patient’s symptoms and individual dosing preferences.

A Study of Acute Renal Failure in the Users of Proton Pump Inhibitors

Background: Proton pump inhibitors are one of the most common classes of medications that act by inhibitinggastric H+/K+ adenosine triphosphatase via covalent binding to the cysteine residues of the proton pump,they provide the most potent acid suppression available. Lansoprazole, pantoprazole, and dexlansoprazolehave the greatest bioavailability and achieve the highest plasma levels. Rabeprazole is the most acid-labilePPI and therefore the most potent, whereas pantoprazole is the least reactive and therefore the least potentPatients and methods: Research data were collected from Al-zahraa teaching hospital/ Wasit province andMorgan teaching hospital/ Babylon province, they include patients with acute renal failure who used/ usingproton pump inhibitors compared with those do not use proton pump inhibitors to know the probable relationbetween acute renal failure and the use of proton pump inhibitors. Results and discussion: Results showedthat only 30 patients of 120 patients with acute renal failure consult the hospital were PPIs users, this mayrefer to presence of a relationship between proton pump inhibitor and acute Renal failure . Previous studiesin this field referred to a similar relationship, a case reports and a recent case series implicating these drugsin acute interstitial nephritis (AIN) and progression to acute renal failure.

Esophageal pH increments associated with post-reflux swallow-induced peristaltic waves show the occurrence and relevance of esophago-salivary reflex in clinical setting.

Following acid perfusion, esophageal pH is restored by swallowed bicarbonate-containing saliva secreted in response to a vagal esophago-salivary reflex. At impedance-pH monitoring, the post-reflux swallow-induced peristaltic wave (PSPW) index puts into relationship timely post-reflux swallows with the number of reflux events: Low values typify reflux-related heartburn (RRH) and lack of on-therapy improvement characterizes proton pump inhibitor (PPI) failure. Considerable esophageal pH increments associated with PSPWs could demonstrate the occurrence of esophago-salivary reflex in clinical setting, while its relevance could be shown by lower esophageal pH increments in PPI-refractory RRH. Prospective multicenter study in patients with PPI-refractory or PPI-responsive RRH evaluated with off-PPI impedance-pH monitoring. Increments in pH associated with PSPWs were measured and the mean calculated to obtain the PSPW-associated ∆pH. The mean PSPW-associated ∆pH in 294 RRH patients was 1.2±0.7 and was lower in 137 PPI-refractory (1.0±0.6) than in 157 PPI-responsive (1.5±0.6) cases (p<0.0001). Lower PSPW-associated ∆pH was independently related to PPI failure at multivariable logistic regression analysis (OR 0.16, 95% CI 0.09-0.26). At ROC analysis, comparing PPI-refractory to PPI-responsive cases the AUC for PSPW-associated ∆pH was 0.76 (95% CI 0.71-0.82), the best cutoff value being 1.2. Considerable PSPW-associated pH increments demonstrate the occurrence of esophago-salivary reflex in clinical setting. Lower increments in PPI-refractory RRH cases show the clinical relevance of esophago-salivary reflex, confirming that PSPW represents a defense mechanism against reflux. PSPW-associated ∆pH can efficiently predict PPI response in patients undergoing off-therapy impedance-pH monitoring.

Clinical management and outcome assessment of generalized anxiety disorder or panic disorder in refractory gastro-esophageal reflux disease: Evidence from a prospective interventional study of benzodiazepines and sertraline

ObjectiveThe aim of the study was to investigate the relationship between Gastro-esophageal reflux diseases (GERD) related symptoms and psychological symptomatology, as well as clinically diagnosed generalized anxiety disorder (GAD) or panic disorder (PD) and effectiveness of Sertraline and benzodiazepines in controlling these conditions. MethodologyA 6 months prospective study was conducted in gastroenterology outpatient department of a tertiary care referral hospital. Refractory GERD was diagnosed by assessing proton pump inhibitor failure over 4 week trial of standard doses of PPIs. Therapy with Benzodiazepines and Sertraline was initiated in patients with refractory GERD having panic and anxiety symptoms associated with refractory GERD. Effectiveness of the therapy was measured using panic and agoraphobia scale and Hamilton anxiety scale. Reduction in the severity of GERD symptoms was assessed using GERD – Health related quality of life scale. ResultsThe occurrence of PD or GAD in patients with refractory GERD in our sample was found to be 68% and 32% respectively. There was a significant decrease in the score of GERD HRQOL after the administration of sertraline and benzodiazepines when compared to the score of GERD HRQOL before administration of interventional drugs (p = 0.001). ConclusionOur study investigated the role of anxiety and panic in refractory GERD and their effect on quality of life. The results indicated that quality of life of patients were highly improved as indicated by severity scores after administration with sertraline and benzodiazepines. The novel therapy of sertraline and benzodiazepines are highly effective in controlling reflux like symptoms and coexisting anxiety and panic disorder in refractory GERD.

Functional heartburn: An underrecognized cause of PPI-refractory symptoms.

Functional heartburn--persistent symptoms of esophageal reflux with no objective evidence of gastroesophageal reflux disease (GERD)--is the most common cause of failure of proton pump inhibitor (PPI) therapy, but it is often overlooked by internists and gastroenterologists.

Role of Reflux in the Pathogenesis of Eosinophilic Esophagitis: Comprehensive Appraisal With Off- and On PPI Impedance-pH Monitoring.

Role of reflux and mechanisms of response to proton pump inhibitor (PPI) therapy in eosinophilic esophagitis (EoE) have not yet been fully elucidated. Comprehensive assessment by impedance-pH monitoring could clarify these issues. Prospective multicenter study comparing EoE patients with healthy controls and gastroesophageal reflux disease cases. Patients with EoE were evaluated off- and on PPI; responsiveness was assessed by histology. Impedance-pH appraisal included chemical clearance, assessed with the postreflux swallow-induced peristaltic wave (PSPW) index, and mucosal integrity measured with mean nocturnal baseline impedance (MNBI). Sixty consecutive patients with EoE were compared with 60 age- and sex-matched healthy controls and 60 subjects with gastroesophageal reflux disease. The number of total refluxes was higher, while the PSPW index was lower in patients with EoE than in healthy controls. Off PPI, a lower MNBI gradient between the mid and distal esophagus distinguished 20 patients with PPI-refractory EoE from 40 patients with PPI-responsive EoE and was a predictor of PPI failure. On PPI, a lower PSPW index was the sole reflux parameter distinguishing PPI-refractory from PPI-responsive EoE; all reflux parameters improved in PPI-responsive patients, whereas the PSPW index was not modified in PPI-refractory cases and was independently associated with PPI-responsiveness. MNBI in the distal and mid esophagus improved much more in PPI-responsive than in PPI-refractory EoE. Reflux plays a role in the pathogenesis of EoE, more relevant in PPI-responsive cases. Low impedance gradient between the mid and distal esophagus may be useful to predict PPI refractoriness. PPIs mainly act by improving chemical clearance, i.e., by an antireflux action supporting long-term prescription in PPI-responsive EoE.

Issue Highlights

Issue Highlights

Most Patients With Gastroesophageal Reflux Disease Who Failed Proton Pump Inhibitor Therapy Also Have Functional Esophageal Disorders

As many as 45% of patients with gastroesophageal reflux disease (GERD) still have symptoms after receiving once-daily proton pump inhibitor (PPI) therapy. We aimed to compare reflux characteristics and patterns between responders and non-responders to once-daily PPI therapy using combined impedance-pH monitoring. Patients who reported heartburn and/or regurgitation at least twice per week for 3 months while receiving standard-dose PPI therapy were assigned to the PPI failure group (n = 16). Patients who reported a complete resolution of symptoms on once-daily PPIs for at least 4weeks were assigned to the PPI success group (n = 13). We collected demographic data and subjects completed the short-form 36 and the GERD health-related quality of life questionnaires. Patients then underwent upper endoscopy and combined esophageal impedance-pH monitoring while on PPI therapy. Four patients in the PPI success group (31%) and 4 patients in the PPI failure group (25%) had abnormal results from the pH test (P = 1.00). Most of the patients in the PPI failure group (75%) were found to have either functional heartburn or reflux hypersensitivity with GERD. Impedance and pH parameters did not differ significantly between the PPI failure and success group. We found no difference in reflux characteristics between patients with GERD who had successful vs failed once-daily PPI therapy. Most patients in the PPI failure group (75%) hadfunctional esophageal disorders.

Modulations in extracellular calcium lead to H+-ATPase-dependent acid secretion: a clarification of PPI failure.

The H+,K+-ATPase was identified as the primary proton secretory pathway in the gastric parietal cell and is the pharmacological target of agents suppressing acid secretion. Recently, we identified a second acid secretory protein expressed in the parietal cell, the vacuolar H+-ATPase (V-type ATPase). The aim of the present study was to further characterize H+-ATPase activation by modulations in extracellular calcium via the calcium sensing receptor (CaSR). Isolated gastric glands were loaded with the pH indicator dye BCECF-AM [2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester] to measure intracellular pH. Experiments were conducted in the absence of sodium and potassium to monitor H+-ATPase-specific transport activity. CaSR was activated with the calcimimetic R568 (400 nM) and/or by modulations in extracellular Ca2+. Elevation in calcium concentrations increased proton extrusion from the gastric parietal cell. Allosteric modification of the CaSR via R568 and calcium increased vacuolar H+-ATPase activity significantly (ΔpH/minlowCa2+(0.1mM) = 0.001 ± 0.001, ΔpH/minnormalCa2+(1.0mM) = 0.033 ± 0.004, ΔpH/minhighCa2+(5.0mM) = 0.051 ± 0.005). Carbachol significantly suppressed calcium-induced gastric acid secretion via the H+-ATPase under sodium- and potassium-free conditions. We conclude that the V-type H+-ATPase is tightly linked to CaSR activation. We observed that proton pump inhibitor (PPI) exposure does not modulate H+-ATPase activity. This elevated blood calcium activation of the H+-ATPase could provide an explanation for recurrent reflux symptoms while taking a PPI therapy. NEW & NOTEWORTHY This study emphasizes the role of the H+-ATPase in acid secretion. We further demonstrate the modification of this proton excretion pathway by extracellular calcium and the activation of the calcium sensing receptor CaSR. The novelty of this paper is based on the modulation of the H+-ATPase via both extracellular Ca (activation) and the classical secretagogues histamine and carbachol (inactivation). Both activation and inactivation of this proton pump are independent of PPI modulation.

Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions.

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist.

Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment.

Background/AimsEsophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment.MethodsNinety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2–4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients.ResultsThe intercellular spaces were dilated in both EE and NERD patients (P < 0.05). The value 0.73 μm could be used as the cut-off DIS value to distinguish patients from controls (area under the curve [AUC] = 0.849, P < 0.01). One thousand seven hundred sixty-four ohms could be used as the cut-off impedance values to distinguish patients from controls (AUC = 0.794, P < 0.01). The baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time (r = −0.527, P < 0.05). There was a weak correlation between DIS and baseline impedance (r = −0.230, P < 0.05). “Baseline impedance > 1764 Ω” was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4–58.9; P < 0.01).ConclusionsThe DIS and decreased baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment.

Weaning of proton pump inhibitors in patients with suspected laryngopharyngeal reflux disease.

To evaluate the feasibility of a proton pump inhibitor (PPI) weaning protocol in a cohort of patients following successful empiric treatment for suspected laryngopharyngeal reflux disease (LPRD). Retrospective chart review. LPRD patients were weaned from PPIs using a standardized weaning protocol. Symptom recurrence rate following PPI wean and present PPI use were determined. All numeric data were analyzed. The setting was a tertiary laryngology practice. The subjects were patients who had a positive response to empiric treatment for LPRD and subsequently were weaned from PPI therapy. Thirty-five patients with suspected LPRD were instructed to wean from PPI after successful empiric treatment of their LPRD symptoms from July 2013 to September 2015. Twenty-three patients (66%) remained symptom-free post-wean. Twelve patients (34%) had symptom recurrence post-wean; of those, 11 of them (92%) needed to go back on a PPI. Median durations of follow-up for the unsuccessful wean group and the successful wean group were 13 (range 6-29) months and 18 (range 6-38) months, respectively. Pre-wean and post-wean reflux symptom index (RSI) scores in the unsuccessful wean group were 7.7 ± 5.6 and 12.9 ± 6 (P = .11). Pre-wean and post-wean RSI scores in the successful wean group were 8.1 ± 6.5 and 8.1 ± 9.0 (P < .99). Body mass index (BMI) was found to be a significant predictor of failure to wean (odds ratio = 0.72, 95% confidence interval = 0.55-0.95) after controlling for age, sex, PPI treatment duration, and PPI regime. None of the other covariates were found to be significant predictors of failure of PPI wean. Approximately 66% of patients who were on PPIs for LPRD were successfully weaned. High BMI was significantly predictive of failure to wean. 4. Laryngoscope, 128:133-137, 2018.

Proton pump inhibitor failure in gastro-oesophageal reflux disease: a perspective aided by the Gartner hype cycle

Some patients with gastro-oesophageal reflux disease (GORD) experience symptoms despite proton pump inhibitor (PPI) treatment. In the early years of their availability, these drugs were thought to be a highly effective treatment for GORD and realisation that symptom relief was often incomplete came as a disappointment. This review considers the evolution of thinking with the aid of the Gartner hype cycle - a graphical depiction of the process of innovation, evolution and adoption of new technologies. Acknowledging that over-simplistic concepts of GORD have been largely responsible for inflated expectations of PPI therapy is an important step forward in establishing how patients with persistent symptoms, despite PPIs, should be assessed and treated.

Clinical Characteristics of Elderly Patients with Refractory Gastroesophageal Reflux Disease

Summary Background Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease, and almost 30% of GERD patients do not respond well to proton pump inhibitor (PPI) therapy. The aim of this study is to evaluate the clinical characteristics of elderly GERD patients who either respond to or resist PPI therapy. Methods A total of 198 patients (75.9 ± 6.4 years, 73.7% males) with GERD receiving PPI treatment were enrolled in this study. Enrolled patients were requested to complete a questionnaire and a personal interview concerning their demographics, comorbidities, symptoms, and endoscopic findings. Results Among the 198 enrolled patients, 135 responded to PPI once or twice daily (Group R), while 63 failed to respond to PPI twice daily (Group F). Cross-group differences were detected for body mass index ( p = 0.042), family status ( p = 0.028), depression (0.7% vs. 7.9%, p = 0.03), compliance (77% vs. 60%, p = 0.015), and hiatal hernia (6.7% vs. 17.5%, p = 0.019). Conclusion PPI failure appears to be significantly influenced by body mass index, family status, depression, compliance, and hiatal hernia of GERD patients.

Tailored therapy for the refractory GERD patients by combined multichannel intraluminal impedance-pH monitoring.

About 30% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI). The reason for the PPI failure in Asian GERD patients has rarely been studied, and the therapy remained unclear. The aims were to explore the possible reasons for PPI failure and to treat these patients with the guidance of 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring. Thirty-nine consecutive patients with refractory GERD were enrolled; 24-h MII-pH monitoring was performed on PPI. The refractory GERD patients were grouped into acid overexposure, non-acid reflux, and functional heartburn after the MII-pH monitoring. Double dose of either PPI or paroxetine was administered to refractory GERD patients within different groups. The number of patients in groups of acid overexposure, non-acid reflux, and functional heartburn was 6, 12, and 21, respectively. The acid overexposure group had the most acid reflux events. Among the acid overexposure group, five (5/6) patients accomplish symptom relief with double dose of esomeprazole. For the patients in non-acid reflux group, double dose of esomeprazole made half (6/12) of the patients obtain symptom relief. For the patients in functional heartburn group, the paroxetine had relieved the symptoms in 14 patients among all the 21 patients. In total, with the guidance of MII-pH monitoring, 64.1% (25/39) of refractory GERD patients accomplished symptom relief. Acid overexposure, non-acid reflux, and functional heartburn were the common reasons for persistent reflux symptoms despite PPI. With the guidance of MII-pH, a tailored therapy could resolve the persistent reflux symptoms among two-third of patients.

Predictors of proton pump inhibitor failure in non-erosive reflux disease: A study with impedance-pH monitoring and high-resolution manometry.

Approximately one-third of gastroesophageal reflux disease (GERD) patients have symptoms resistant to proton pump inhibitor (PPI). We used the high-resolution manometry (HRM) and multichannel intraluminal impedance-pH (MII-pH) monitoring to investigate potential predictors of PPI failure in non-erosive reflux disease (NERD) patients. One hundred and seventeen NERD patients were included, within which there were 44 PPI failure patients. The symptomatic questionnaire GerdQ, HRM and 24-hour MII-pH monitoring were performed before PPI therapy. PPI failure was defined as persistent reflux symptoms for more than 1 day during the last week on esomeprazole (20 mg twice daily) for continuous 4 weeks. The predictors for PPI failure were investigated by multivariable logistic regression analysis. Proton pump inhibitor failure patients had lower body mass index (BMI) and more concomitant functional dyspepsia (FD) symptoms. PPI failure patients had a higher percentage of type I esophagogastric junction (EGJ) morphology (p = 0.005), increased EGJ augmentation (p = 0.000), higher prevalence of esophageal motility disorders (p = 0.005) and a higher ratio of negative symptom index (SI, p = 0.000). Multivariable regression analysis showed that concomitance of FD symptoms, EGJ augmentation and negative SI were independent risk factors for PPI failure in NERD. Approximately half of PPI failure patients were found to have esophageal motility disorders in HRM. The independent risk factors for PPI failure in NERD were concomitant FD symptoms, increased EGJ augmentation and negative SI.

The Relationship Between Type 2 Diabetes Mellitus and Proton Pump Inhibitor Failure in Patients With Gastroesophageal Reflux Disease

Introduction: There have been a limited number of studies that evaluated risk factors for proton pump inhibitor (PPI) failure in patients with type 2diabetes mellitus (DM) and concomitant gastroesophageal reflux disease (GERD). The aim of the study was to determine the predictive risk factors for PPI failure among patients diagnosed with type 2 DM and GERD. Methods: Using a population-based study, 398 patients diagnosed with GERD who were treated with a PPI between 2004 and 2014 were included in the study. Patients were divided based on the presence of type 2 DM (diagnosed >1 year prior to enrollment into the study) and were further classified depending on their response to PPI therapy into PPI-responders and PPI-failure. PPI failure was defined as the need to treat with more than once daily PPI or the addition of other anti-reflux agents to ncontrol GERD-related symptoms. Results: A total of 398 patients with GERD were included in the study and of those 65 patients (16.3%) also had the diagnosis of type 2 DM. A total of 30 patients had failed PPI once daily. Between the DM and non DM group, 93 patients (23.4%) had failed PPI therapy and 305 (76.6%) had good response to PPI therapy. Most of the patients were females (61.5%) and mean age of the patients was 53.9 years (range 22-83). Poor diabetic control was measured by HgA1c, and shown to increase the risk of PPI failure by almost 50% (OR 1.47 95% CI 1.03-2.08, p=0.03). Also, in all GERD patients, PPI failure depended on female gender and depression. Males were half as likely to fail PPI therapy (OR 0.56 95% CI 0.34-0.93, p=0.03) and depression carried an odds ratio which was twice that of the normal population (OR 2.00 95% CI 1.19-3.36 p=0.01). Type II diabetes, duration of diabetes, and type of anti-diabetic medication prescribed were not statistically significantly associated with PPI failure.Table 1: Risk factors with P <0.05Conclusion: In GERD patients, female gender and depression were predictive factors of PPI failure. In GERD patients with type 2 DM, poor control of DM as measured by HgA1c was predictive of PPI failure.

The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum.

Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy.