Multicentre prospective study to evaluate effectiveness and safety of gel-forming and hyaluronic-acid containing chewable tablets as add-on treatment in patients with gastroesophageal reflux disease (GERD) symptoms and unsatisfying proton pump inhibitor therapy.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease which in the majority of patients is treated with proton pump inhibitors (PPI). However, up to 45% of the patients remain symptomatic on a standard dose of PPI. This study investigated the effectiveness and safety of an add-on therapy with the gel-forming chewable tablet Sobrade® in patients unsatisfied with PPI treatment. The bioadhesive gel covers the oesophagus and thereby protects the mucosa from reflux events. METHODS: 47 patients with symptomatic GERD despite PPI treatment participated in this study. The gel-forming tablets were taken up to four times daily after meals and prior to bedtime. Severity and frequency of GERD symptoms were evaluated during two onsite visits prior and following 14 days of treatment and used to calculate the GERD score of the Reflux Disease Questionnaire. Furthermore, patients recorded symptoms as well as onset and duration of symptoms relief daily in their electronic dairies. Effectiveness of treatment was analysed using non-parametric paired Wilcoxon test. In addition, anchor-based minimal important differences (MID) were assessed. RESULTS: Treatment resulted in significant reduction of GERD symptoms. Severity and frequency of 8 of the 9 assessed symptoms improved significantly during the treatment phase whereby most pronounced improvement was observed for heartburn. In agreement, all three subscales of the GERD score improved significantly. MID results suggest that patients considered a mean improvement of symptoms > 30% of initial severity as beneficial. Self-assessments by patients revealed first significant improvements of symptoms like heartburn and regurgitation from day 5 of treatment onwards. 49% of patients reported relief of symptoms within 15 min which lasted on average for 3.5 h. During the study no treatment emergent adverse events were reported and in 98% of all cases tolerability of the product was rated as very good or good. CONCLUSIONS: This study revealed a pronounced improvement of the symptoms after add-on treatment with the gel-forming medical device. The very good safety and tolerability profile indicate an advantageous risk-benefit ratio. TRIAL REGISTRATION: This non-interventional study was prospectively positively evaluated by the responsible ethic-committees.

Proton pump inhibitors in eosinophilic esophagitis (EoE) related to oral immunotherapy: is it as effective as in other EoE?

Oral immunotherapy (OIT) may induce eosinophilic esophagitis (EoE). Proton pump inhibitors (PPIs) are an effective treatment for EoE. However, the effect of PPI treatment is not well established in patients with EoE induced by OIT. Our primary aim was to compare the clinical, endoscopic, and histological response rates to PPIs in children with EoE induced by OIT (EoE+OIT) versus EoE patients without OIT (EoE-OIT). The secondary aims are to describe the clinical and histological features of EoE+OIT. Demographic, clinical, endoscopic, and histological findings of patients with EoE in the gastroenterology clinic at Shamir Medical Center between March 2015 and December 2022 were collected. Comparisons were performed between EoE+OIT and EoE-OIT patients. The study included 42 children (74% male, mean age 11.2), of whom 31 had EoE-OIT and 11 had EoE+OIT. There were no significant differences between groups regarding sex, comorbidities, symptoms, or endoscopic and histological characteristics at diagnosis. All 42 children were treated with PPIs after diagnosis with or without diet changes. The rates of any clinical response were 83.9% and 90.1% in the EoE-OIT group and EoE+OIT group, respectively (p = 1.0). The rate of any endoscopic response was 74.2% for EoE-OIT and 81.8% for EoE+OIT (p = 0.54). Histologically, PPIs were even more effective in the EoE+OIT group, where only 18.2% had no histological response at all compared to 51.6% in the EoE-OIT group (p = 0.1). CONCLUSION: PPI treatment is as effective in EoE with OIT as it is in EoE due to other etiologies. WHAT IS KNOWN: • Proton pump inhibitor (PPI) treatment is effective for achieving clinical response and histologic remission in some patients with eosinophilic esophagitis (EoE). • EoE has also been reported to be triggered by oral immunotherapy (OIT). WHAT IS NEW: • PPI treatment in EoE with OIT is as effective as treatment for EoE due to other etiologies.

Australian data on the utilisation and duration on treatment of ibrutinib with a proton pump inhibitor in patients with relapsed or refractory chronic lymphocytic leukaemia.

In Australia, over half of patients with relapsed/refractory chronic lymphocytic leukaemia treated with ibrutinib use concomitant proton pump inhibitors (PPIs). High gastric pH reduces the bioavailability of some Bruton tyrosine kinase inhibitors. There was no difference in duration on ibrutinib with or without concomitant PPI (unadjusted P = 0.61; adjusted hazard ratio: 1.23, 95% confidence interval: 0.75-2.02, P = 0.411). PPI use does not affect ibrutinib treatment persistence.

[Clinical Management of Non-Variceal Upper Gastrointestinal Bleeding].

Non-variceal upper gastrointestinal bleeding (NVUGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of varices. As a common clinical problem, NVUGIB entails a heavy burden on the healthcare system. In addition to endoscopic hemostasis, evaluation and treatment before and after endoscopy are also of critical importance for the clinical management of NVUGIB patients. In recent years, based on the rapid development of endoscopic technology and clinical management of NVUGIB, the research evidence and clinical guidelines have been updated internationally, while some clinical decisions remain controversial. In this article, we mainly reviewed and discussed the current status of NVUGIB patient management before, during, and after endoscopy, aiming to deepen the understanding of the disease for clinicians, and to promote standardized management of patients with NVUGIB.

Reducing Inappropriate Proton Pump Inhibitors Use for Stress Ulcer Prophylaxis in Hospitalized Patients: Systematic Review of De-Implementation Studies.

BACKGROUND: A large proportion of proton pump inhibitor (PPI) prescriptions, including those for stress ulcer prophylaxis (SUP), are inappropriate. Our study purpose was to systematically review the effectiveness of de-implementation strategies aimed at reducing inappropriate PPI use for SUP in hospitalized, non-intensive care unit (non-ICU) patients. METHODS: We searched MEDLINE and Embase databases (from inception to January 2020). Two authors independently screened references, performed data extraction, and critical appraisal. Randomized trials and comparative observational studies were eligible for inclusion. Criteria developed by the Cochrane Effective Practice and Organisation of Care (EPOC) group were used for critical appraisal. Besides the primary outcome (inappropriate PPI prescription or use), secondary outcomes included (adverse) pharmaceutical effects and healthcare use. RESULTS: We included ten studies in this review. Most de-implementation strategies contained an educational component (meetings and/or materials), combined with either clinical guideline implementation (n = 5), audit feedback (n = 3), organizational culture (n = 4), or reminders (n = 1). One study evaluating the de-implementation strategy effectiveness showed a significant reduction (RR 0.14; 95% CI 0.03-0.55) of new inappropriate PPI prescriptions. Out of five studies evaluating the effectiveness of de-implementing inappropriate PPI use, four found a significant reduction (RR 0.21; 95% CI 0.18-0.26 to RR 0.76; 95% CI 0.68-0.86). No significant differences in the occurrence of pharmaceutical effects (n = 1) and in length of stay (n = 3) were observed. Adverse pharmaceutical effects were reported in two studies and five studies reported on PPI or total drug costs. No pooled effect estimates were calculated because of large statistical heterogeneity between studies. DISCUSSION: All identified studies reported mainly educational interventions in combination with one or multiple other intervention strategies and all interventions were targeted at providers. Most studies found a small to moderate reduction of (inappropriate) PPI prescriptions or use.

Clinical characteristics and factors related to antibiotic-associated diarrhea in elderly patients with pneumonia: a retrospective cohort study.

BACKGROUND: Antibiotic-associated diarrhea (AAD) is a common problem among elderly inpatients because many elderly patients are admitted for pneumonia or other conditions that necessitate antibiotic treatment. In the super aging population, more patients are suffering from pneumonia than before, but the incidence or risk factors for AAD among many elderly patients have not been well scrutinized. METHODS: We conducted a retrospective cohort study of elderly patients diagnosed with pneumonia from April 2014 to March 2019 who were admitted to the Department of General Medicine of a Tertiary Care Hospital in Japan. Patients (≥ 65 years of age) who were diagnosed with bacterial pneumonia or aspiration pneumonia and treated with antibiotics were included. We defined AAD by diarrhea with more than three loose or watery stools per day and included patients who had these symptoms for either one day or two or more consecutive days. We also assessed the length of hospital stay and in-hospital mortality. The potential risk factors for AAD included age, sex, body weight, body mass index, smoking, alcohol, activities of daily living (ADL),　comorbidities, vital signs, laboratories, the severity of pneumonia, antibiotic and other medication use. RESULTS: There were 1,067 patients, the mean age was 83 years, and men accounted for 59 %. ß-Lactamase inhibitors were frequently prescribed antibiotics in 703 patients (66 %), and proton pump inhibitors (PPIs) were also commonly administered (48 %). AAD developed in 322 patients (30 %). The multivariate logistic regression model showed that ß-lactamase inhibitors (OR 1.43, 95 % CI 1.05-1.95) and PPIs (OR 1.37, 95 % CI 1.03-1.83) were associated with AAD as well as age (OR 1.03 per year, 95 % CI 1.01-1.05). CONCLUSIONS: AAD was common among elderly inpatients with pneumonia, and ß-lactamase inhibitors and PPIs were associated with AAD. Strict use of such medication should be considered to decrease the risk of AAD.

Emerging drugs for eosinophilic esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is rare but incidence and prevalence is increasing. EoE is characterized by eosinophilic inflammation of the esophagus causing gastrointestinal symptoms such as abdominal pain, vomiting, reflux, dysphagia, and food impactions. If untreated, remodeling and fibrosis of the esophagus can occur and stricture formation may result. Current treatment options are limited to food-restriction diets or medications including proton pump inhibitors (PPIs) or swallowed corticosteroids. Significant progress has been made in understanding the underlying mechanisms of EoE allowing for development of drugs that target specific points in EoE pathways. Investigation of these drugs is early with few controlled studies, but many show promise as future treatments. Areas covered: This review will provide an up to date discussion of current therapies and investigational drugs for EoE. Articles used in this review were retrieved from PubMed. Ongoing or completed clinical trials were obtained through clinicaltrials.gov and review of the PharmaProjects database. Expert Opinion: Multiple therapeutic targets have been identified and several have shown efficacy. Work is needed to define appropriate trial outcome measures. Collaboration between government agencies, patient advocacy groups, and investigator-led consortia is critical for completing new clinical trials which should pave the way for new therapies in clinical practice.

New Approaches to Diagnosis and Treatment of Functional Dyspepsia.

PURPOSE OF REVIEW: The purpose of this article is to review the recent literature and discuss the new approaches to the diagnosis and treatment of functional dyspepsia (FD). RECENT FINDINGS: According to the recent American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guideline for dyspepsia, Helicobacter pylori (H. pylori) eradication is recommended as a first treatment option, and proton pump inhibitors (PPIs), tricyclic antidepressants, and prokinetics are listed as second-line therapy. On the other hand, in the Japanese guideline for FD, PPIs and prokinetics are recommended as the first-line treatment. In Japan, acotiamide, a recently launched prokinetic, showed significant efficacy in several clinical trials performed either in Japan or Europe. Regarding non-pharmacological treatment, recent topics include acupuncture, electrical stimulation, gastric peroral endoscopic myotomy, and meal and lifestyle modification. These treatments have provided significant efficacy, which provides some insights into the main pathophysiology of this disease. Although FD is common among functional gastrointestinal disorders, it is not easy to relieve the dyspeptic symptoms of FD patients. Combinations of pharmacological and non-pharmacological treatment options are expected.

Impedance-pH monitoring on medications does not reliably confirm the presence of gastroesophageal reflux disease in patients referred for antireflux surgery.

INTRODUCTION: The gold standard for the objective diagnosis of gastroesophageal reflux disease (GERD) is ambulatory-pH monitoring off medications. Increasingly, impedance-pH (MII-pH) monitoring on medications is being used to evaluate refractory symptoms. The aim of this study was to determine whether an MII-pH test on medications can reliably detect the presence of GERD. METHODS: Patients referred for persistent reflux symptoms despite pH confirmed adequate acid suppression (DeMeester score ≤14.7) were reviewed retrospectively. All patients who originally had MII-pH testing on medications were re-evaluated with an off medication Bravo-pH study. Acid exposure results (defined by off medication Bravo) were compared to the original on medication MII-pH. RESULTS: There were 49 patients who met study criteria (median age 51). Patients had normal acid exposure during their MII-pH test on medications (average DMS 4.35). Impedance was abnormal (normal ≤47) in 25 of the 49 patients (51%). On subsequent Bravo-pH off medications, 37 patients (75.7%) showed increased esophageal acid exposure (average DMS 36.4). Bravo-pH testing was abnormal in 84% of patients with abnormal MII testing and in 67% with normal MII testing. The sensitivity and specificity of an abnormal MII-pH on medications for increased esophageal acid exposure off medications was 56.8 and 66.7%, respectively. The positive predictive value of confirming GERD from an abnormal MII-pH on medications is 84%, while the negative predictive value is 33.3%. A receiver operating characteristic (ROC) curve was generated and the area under the curve was 0.71, indicating that MII-pH on medications is a fair test (0.7-0.8) in diagnosing pathologic GERD. CONCLUSION: Compared to the gold standard, MII-pH on medications does not reliably confirm the presence of GERD. Excellent outcomes with antireflux surgery are dependent on the presence of GERD; thus, patients should not be offered antireflux surgery until GERD is confirmed with pH testing off medications.

The TEMPO Trial at 5 Years: Transoral Fundoplication (TIF 2.0) Is Safe, Durable, and Cost-effective.

BACKGROUND: Questions remain about the therapeutic durability of transoral incisionless fundoplication (TIF). In this study, clinical outcomes were evaluated at 5 years post-TIF 2.0. METHODS: A total of 63 chronic gastroesophageal reflux disease (GERD) sufferers with troublesome symptoms refractory to proton pump inhibitor (PPI) therapy, absent or ≤2 cm hiatal hernia, and abnormal esophageal acid exposure were randomized to the TIF group or PPI group. Following the 6-month evaluation, all patients in the PPI group elected for crossover to TIF; therefore, all 63 patients underwent TIF 2.0 with EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation and atypical symptoms at the 5-year follow-up. Secondary outcomes were improvement in symptom scores, PPI use, reoperations, and patient health satisfaction. The cost-effectiveness of TIF 2.0 was also estimated. RESULTS: Of 63 patients, 60 were available at 1 year, 52 at 3 years, and 44 at 5 years for evaluation. Troublesome regurgitation was eliminated in 88% of patients at 1 year, 90% at 3 years, and 86% at 5 years. Resolution of troublesome atypical symptoms was achieved in 82% of patients at 1 year, 88% at 3 years, and 80% at 5 years. No serious adverse events occurred. There were 3 reoperations by the end of the 5-year follow-up. At the 5-year follow-up, 34% of patients were on daily PPI therapy as compared with 100% of patients at screening. The total GERD Health-related quality-of-life score improved by decreasing from 22.2 to 6.8 at 5 years ( P < .001). CONCLUSION: In this patient population, the TIF 2.0 procedure provided safe and sustained long-term elimination of troublesome GERD symptoms.

Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients.

BACKGROUND: Posttransplantation bone disease is a significant problem, with few well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated with hip fracture in the general population and are widely prescribed for kidney transplant recipients. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: From the US Renal Data System, we identified from diagnoses and procedures 231 kidney transplant recipients with a first hip fracture. Cases were matched at the hip fracture index date with 15,575 controls on age, sex, race, and transplantation year. PREDICTOR: PPI use. OUTCOMES: First hip fracture. RESULTS: In the year prior to the index date, a PPI was prescribed to 65.4% of cases and 57.4% of controls. Additionally, in 34.6% of cases and 28.9% of controls, a PPI was prescribed for >80% of the year preceding the index date (higher PPI users). Unadjusted ORs of hip fracture associated with any and higher PPI use were 1.55 (95% CI, 1.18-2.05) and 1.65 (95% CI, 1.2-2.27), respectively. When adjusted for baseline demographic, clinical, and pharmacologic covariables, any and higher PPI use remained associated with hip fracture, with ORs of 1.39 (95% CI, 1.04-1.84) and 1.41 (95% CI, 1.02-1.95), respectively. LIMITATIONS: Potential residual confounding through either incorrectly ascertained or unavailable confounders; cohort limited to Medicare beneficiaries receiving low-income subsidy. CONCLUSIONS: In summary, PPI use was associated with hip fracture risk in the US kidney transplant population.

Gastroesophageal reflux disease with proton pump inhibitor use is associated with an increased risk of osteoporosis: a nationwide population-based analysis.

UNLABELLED: Gastroesophageal reflux disease (GERD) with proton pump inhibitor (PPI) use is associated with an increased risk of osteoporosis. The risk of hip fracture is not increased in GERD patients with PPI use. INTRODUCTION: The relationship between GERD with PPI treatment and the risk of osteoporosis is unclear. We aimed to determine the risk of developing osteoporosis in patients diagnosed with GERD. METHODS: Patients diagnosed with GERD and received PPI treatment between 2000 and 2010 were identified from the Longitudinal Health Insurance Database as the study cohort (n = 10,620), which was frequency matched with the comparison cohort (n = 20,738) sampled from the general population according to age, sex, index year, and comorbidities. Both cohorts were followed until the end of 2011. The risk of osteoporosis was evaluated in both groups by using Cox proportional hazards regression models. RESULTS: The GERD patients with PPI treatment had a greater incidence (31.4 vs 20.7 per 1000 person-year; crude hazard ratio [cHR] 1.51; 95 % confidence interval [CI] 1.40-1.63) and a higher risk (adjusted HR [aHR] 1.50; 95 % CI 1.39-1.62) of osteoporosis than that of the comparison cohort. However, the overall incidence of hip fracture was not different between the GERD with PPI use and the control cohorts (aHR 0.79; 95 % CI 0.53-1.18). CONCLUSION: GERD with PPI use is associated with an increased risk of osteoporosis. The findings of our study do not support an increased risk of hip fracture in GERD patients treated with a PPI.

Development of quality measures for the care of patients with gastroesophageal reflux disease.

BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) is a common and costly disorder. Symptoms attributed to GERD have a wide spectrum of presentations and complications that have led to complex diagnostic and management algorithms. As such, there is considerable variation in clinical approaches to GERD. In contrast to multiple published guidelines for the management of GERD, there are few validated GERD quality measures. The objective of this study was to use a well-described, formal methodology to develop valid, physician-led quality measures for all aspects of care for patients with GERD. METHODS: Quality measures were identified from the literature, consensus guidelines, and GERD experts. Eight clinical experts ranked potential measures for validity on the basis of the RAND/University of California, Los Angeles Appropriateness Methodology. RESULTS: Of the 52 proposed quality measures, 24 were rated as valid, and 1 new measure was developed. These valid measures were related to initial diagnosis and management (9), monitoring (3), further diagnostic testing (4), proton pump inhibitor refractory symptoms (2), symptoms of chest pain (1), erosive esophagitis (3), esophageal stricture or ring (1), and surgical therapy (2). Fifteen of these measures were ranked with the highest validity. Twenty-seven measures were determined to be equivocal; 89% of these were extracted from guidelines that were based on low or moderate level evidence. CONCLUSIONS: We used RAND/University of California, Los Angeles Appropriateness Methodology to develop quality measures for GERD care. By examining performance on these valid, formally developed quality measures, clinical practices and individual providers can assess their adherence with them and direct quality improvement efforts accordingly.

Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study.

BACKGROUND: Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 9,818 individuals from the general population (Rotterdam Study). PREDICTOR: PPI use and H2RA use compared to no use. OUTCOMES & MEASUREMENTS: Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use. RESULTS: Serum magnesium level was 0.022 mEq/L lower in PPI users (n=724; 95% CI, -0.032 to -0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n=36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n=270), PPI use was associated with a further increased risk of hypomagnesemia (n=5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n=250) also had a lower serum magnesium level (-0.016 [95% CI, -0.032 to -0.002] mEq/L) and increased risk of hypomagnesemia (n=12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics. LIMITATIONS: Cross-sectional analysis with single serum magnesium measurement. CONCLUSIONS: PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics.

Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: the TEMPO Randomized Clinical Trial.

BACKGROUND: Incomplete control of troublesome regurgitation and extraesophageal manifestations of chronic gastroesophageal reflux disease (GERD) is a known limitation of proton pump inhibitor (PPI) therapy. This multicenter randomized study compared the efficacy of transoral incisionless fundoplication (TIF) against PPIs in controlling these symptoms in patients with small hiatal hernias. METHODS: Between June and August 2012, 63 patients were randomized at 7 US community hospitals. Patients in the PPI group were placed on maximum standard dose (MSD). Patients in the TIF group underwent esophagogastric fundoplication using the EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation or extraesophageal symptoms. Secondary outcomes were normalization of esophageal acid exposure (EAE), PPI usage and healing of esophagitis. RESULTS: Of 63 randomized patients (40 TIF and 23 PPI), 3 were lost to follow-up leaving 39 TIF and 21 PPI patients for analysis. At 6-month follow-up, troublesome regurgitation was eliminated in 97% of TIF patients versus 50% of PPI patients, relative risk (RR) = 1.9, 95% confidence interval (CI) = 1.2-3.11 (P = .006). Globally, 62% of TIF patients experienced elimination of regurgitation and extraesophageal symptoms versus 5% of PPI patients, RR = 12.9, 95% CI = 1.9-88.9 (P = .009). EAE was normalized in 54% of TIF patients (off PPIs) versus 52% of PPI patients (on MSD), RR = 1.0, 95% CI = 0.6-1.7 (P = .914). Ninety percent of TIF patients were off PPIs. CONCLUSION: At 6-month follow-up, TIF was more effective than MSD PPI therapy in eliminating troublesome regurgitation and extraesophageal symptoms of GERD.

Biopsy-proven acute interstitial nephritis, 1993-2011: a case series.

BACKGROUND: Acute interstitial nephritis (AIN) is an important cause of acute kidney injury, especially in hospitalized patients. The cause and outcome of AIN, particularly that due to drugs, is changing with prevalent medication use. The effectiveness of steroids for treatment of AIN is debated. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 133 patients with biopsy-proven AIN from 1993 through 2011 at a single center. OUTCOMES: Recovery of kidney function by 6 months, either complete, partial, or none. Complete recovery was defined as improvement in serum creatinine level to within 25% of baseline (or < 1.4 mg/dL), and partial recovery, as a ≥ 50% decrease in serum creatinine level from its peak value but not reaching within 25% of its baseline value. RESULTS: Causes of AIN included drugs (70%), autoimmune diseases (20%), and infections (4%). Drug-induced AIN was due to antibiotics in 49%, proton pump inhibitors (PPIs) in 14%, and nonsteroidal anti-inflammatory drugs (NSAIDs) in 11%. Overall, the top 3 drug causes were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%). Patients with drug-induced compared to non-drug-induced AIN were older and had higher baseline kidney function, but more severe acute kidney injury. Patients with PPI-induced AIN were older, were less symptomatic, and had longer durations of drug exposure and longer delays in getting kidney biopsy and steroids than for antibiotic-induced or NSAID-induced AIN. At 6 months postbiopsy, 49% of patients with drug-induced AIN treated with steroids achieved complete recovery; 39%, partial recovery; and 12%, no recovery. Correlates of poor recovery included a longer duration of drug exposure (15 vs 30 vs 130 days for complete, partial, and no recovery, respectively; P = 0.04) and longer delay in starting steroid therapy (8 vs 11 vs 35 days, respectively; P = 0.05). LIMITATIONS: Retrospective study, selection bias in patients who had kidney biopsy, single-center experience. CONCLUSIONS: The cause of AIN may be shifting; PPIs are emerging as an important contributor to this disease. Delays in discontinuation of the culprit drug and in initiating steroid treatment adversely affect recovery of kidney function.

Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends.

Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.

Proton Pump Inhibitor Prescription in Nursing Home Residents: Prevalence, Appropriateness, and Associated Factors-A Secondary Data Analysis from Three German Regions and the Impact of Guideline Recommendations.

Despite reliable evidence of adverse drug effects, the substantially increased prescription rates of proton pump inhibitors (PPIs) remain at a high level. This study analyzed the appropriateness of PPI prescriptions among residents of nursing homes in three regions of Germany. Baseline data of a cluster-randomized controlled trial were used to determine the prevalence of PPI prescriptions, the validity of indications, and the adequacy of the prescribed dosages according to 1. their drug approvals and 2. valid recommendation guidelines. Regression analyses were conducted to assess associated factors. A total of 437 residents in 37 nursing homes were included (mean age 83 ± 9.2 years, 72% women). The PPI prescription prevalence was 44% (n = 193). In 52/193 (27%) there was no adequate indication, and in 54 (39%) of 138 indicated PPI prescriptions it was overdosed. Yet, in only less than one-third (28%) of "adequate" prescriptions, the indication was according to the PPI approvals, whereas the majority (72%) were off-label indications in line with valid guideline recommendations. Non-indicated PPI prescription was associated with the total number of prescribed drugs (OR 1.32; 95% CI 1.18-1.62; p = 0.013). There were no associations with age, level of care dependency, cognitive impairment, prescription of psychotropic drugs, number of chronic diseases, number of physicians' consultations, or study region. To conclude, in 55%, the high prescription prevalence among residents was either not indicated or overdosed. In total, only 20% (39/193) of cases of PPI use complied with the approved indications. There is a need for quality control of 1. PPI administration in German nursing homes, and 2. of guideline recommendations expanding the off-label PPI use by 72% within the indication scale, predominantly from wide prescription for low-dose ASA.

Factors predicting the presence of small bowel lesions in patients with obscure gastrointestinal bleeding.

AIM: To identify the predictive factors for the presence of small bowel lesions in patients with obscure gastrointestinal bleeding (OGIB). METHODS: A total of 242 patients with OGIB (overt 149: occult 93) were retrospectively included in the present study. Capsule endoscopy (CE) was carried out to investigate the small bowel, and detected lesions were classified according to the P0-P2 system. Only P2 lesions were defined as significant lesions. Univariate and multivariate logistic regression analyses were carried out to define the predictive factors for the presence of small bowel lesions. RESULTS: In patients with overt OGIB, chronic kidney disease (CKD) ≥stage 4 (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.45-11.1, P = 0.007) was identified as an independent predictor of the presence of vascular lesions, and a history of non-steroidalanti-inflammatory drug (NSAID) use as that of erosive/ulcerated lesions (OR 4.73; 95% CI 1.47-15.2, P = 0.009). However, in patients with occult OGIB, no significant predictors of the presence of vascular lesions were identified, whereas a history of low-dose aspirin (LDA) (OR 3.57; 95% CI 1.21-10.5, P = 0.02) and proton pump inhibitor (PPI) use (OR 3.18; 95% CI 1.02-9.92, P = 0.05) were identified as independent predictors of the presence of erosive/ulcerated lesions. CONCLUSIONS: Our results indicated that bleeding pattern and clinical characteristics could contribute to predicting the origin of OGIB.

The Association between Proton Pump Inhibitors and the Effectiveness of CDK Inhibitors in HR+/HER- Advanced Breast Cancer Patients: A Systematic Review and Meta-Analysis.

There have been many clinical questions regarding whether the use of proton pump inhibitors (PPIs) could deteriorate the effects of cyclin-dependent kinase inhibitors (CDKIs) in HR+/HER2- advanced breast cancer patients. We performed a systematic review and meta-analysis of this clinical question, including studies enrolling HR+/HER2- metastatic breast cancer patients treated with CDKIs (Palbociclib or Ribociclib) and reporting at least one comparative survival outcome, either overall survival (OS) or progression-free survival (PFS), between concomitant PPI users and non-users. Eight studies met the eligibility criteria, with a total of 2584 patients included (PPI users: 830, PPI non-users: 1754), demonstrating that concomitant PPI use was associated with significantly higher risks of all-cause mortality (HR = 2.03; 95% CI, 1.49 to 2.77; I2 = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I2 = 59%) in breast cancer patients taking Palbociclib. In contrast, there were no significant survival impacts of PPIs on Ribociclib (HR = 1.46; 95% CI, 0.91 to 2.34; I2 = 36%). Additionally, there was no significant difference in the risk associated with CDKI dose reduction due to drug toxicity (RR = 1.12; 95% CI, 0.97 to 1.29). Therefore, when HR+/HER2- advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib.