Patients Receiving Proton Pump Inhibitors Research Articles

Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations.

The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients received Clostridium butyricum therapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on the efficacy of chemoimmunotherapy combinations varied based on tumor-programmed cell death ligand 1 (PD-L1) expression. The survival benefit of CBM588 in the PD-L1 <1% cohort was higher than that in the PD-L1 1-49% and PD-L1 ≥ 50% cohorts. Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy.

Dynamic assessment of serum chromogranin A and treatment response with abiraterone acetate in metastatic castration-resistant prostate cancer.

Elevated serum chromogranin A (CGA) is associated with intrinsic or treatment-related neuroendocrine differentiation (NED) in men with metastatic castration-resistant prostate cancer (mCRPC). Fluctuations in serum CGA during treatment of mCRPC have had conflicting results. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with abiraterone acetate (AA) therapy. Between June 2013 and August 2015, 92 men with mCRPC were enrolled in a prospective trial with uniform serum CGA processing performed before initiating abiraterone acetate/prednisone (AA/P) and serially after 12 weeks of AA/P treatments. Serum CGA was measured using a homogenous automated immunofluorescent assay. Patients receiving proton pump inhibitors or with abnormal renal function were excluded due to possible false elevations of serum CGA (n = 21 excluded), therefore 71 patients were analyzed. All patients underwent a composite response assessment at 12-weeks. Kaplan-Meier estimates and Cox Regression models were used to calculate the association with time-to-treatment failure analyses and overall survival. An increase in chromogranin was associated with a lower risk of treatment failure (hazard ratio [HR]: 0.52, p = 0.0181). The median CGA/PSA ratio was 7.8 (2.6-16.0) and an elevated pretreatment CGA/PSA ratio above the median was associated with a lower risk of treatment failure (HR: 0.54 p value = 0.0185). An increase in CGA was not found to be associated with OS (HR: 0.71, 95% CI: 0.42-1.21, p = 0.207). An elevated baseline CGA/PSA ratio was not associated with OS (HR: 0.62, 95% CI: 0.37-1.03, p = 0.062). An increase in PSA after 12 weeks of treatment was associated with an increased risk of treatment failure (HR: 4.14, CI: 2.21-7.73, p = < 0.0001) and worse OS (HR: 2.93, CI: 1.57-4.45, p = < 0.0001). We show that an increasing chromogranin on AA/P and an elevated baseline CGA/PSA in patients with mCRPC were associated with a favorable response to AA/P with no changes in survival. There may be limited clinical utility in serum CGA testing to evaluate for lethal NED as AA/P did not induce lethal NED in this cohort. This highlights that not all patients with an increasing CGA have a worse OS.

Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors

ABSTRACT Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing. Clostridium butyricum therapy using C. butyricum MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.

Gastric mucosa condition in patients with coronary artery disease and high risk of gastrointestinal bleeding (register REGATTA-1)

To assess the upper gastrointestinal mucosal condition by endoscopic and histological methods in patients with stable coronary arteries disease receiving long-term antiplatelet therapy with gastrointestinal bleeding (GIB) history or with high risk of this complication. The study included patients from the single-center prospective registry of long-term antithrombotic therapy REGATTA-1. The gastric mucosa endoscopic examination with biopsy was performed in 20 patients with gastrointestinal bleeding history less than 1 year ago and in 24 patients without GIB, which have concomitant risk factors such as erosions and ulcers history and/or persistent dyspepsia clinical signs. The mucosal condition (erosions and ulcers) was estimated using a modified Lanz scale. The presence of Helicobacter pylori was determined by Histological verification. The inflammatory process characteristics were evaluated according to the modified Sydney classification. All participants received antithrombotic therapy at the time of esophagogastroduodenoscopy; 81.8% of patients received proton pump inhibitors. Chronic inflammation (93.2%), atrophy (59.1%), multiple erosions (45.5%) or ulcers (18.2%) were the most frequent endoscopic finding. H. pylori infection, found in mucosal samples in 90.9% of patients was one of the most important pathogenesis mechanism, which support the gastrointestinal mucosa damage. Mucosal damage endoscopic signs remains despite long-term proton pump inhibitors therapy in patients with coronary arteries disease and concomitant GIB risk factors, receiving antithrombotic therapy. H. pylori contamination may be the cause of these changes. Therefore, its active screening and eradication is necessary in such patients.

Objective Evidence of Gastro-Esophageal Reflux Disease is Rare in Patients with Autoimmune Gastritis

Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG. Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared. Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit. Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated.

Is there an increased risk for dementia in older patients receiving proton pump inhibitors?

Is there an increased risk for dementia in older patients receiving proton pump inhibitors?

Clinico-pathological characteristics of eosinophilic esophagitis in Jordanian children.

IntroductionEosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder manifested by symptoms of impaired esophageal function and hypereosinophilic esophageal inflammation. It is believed that the number of patients being diagnosed globally is increasing.AimTo describe the frequency and clinicopathological features of EoE in Jordanian children.Material and methodsA retrospective review of all paediatric patients with eosinophilic esophagitis diagnosed and followed up at our paediatric gastroenterology service at King Abdullah University Hospital between January 2015 and January 2020.ResultsDuring the study period, 21 patients were diagnosed with EoE out of 700 diagnostic endoscopic procedures. Only 1 (4.8%) female was diagnosed. The average age at presentation was 9.5 years (age range: 1–16 years). The most common manifestation was solid food dysphagia (15, 71.4%), followed by food impaction and vomiting (11, 52.4% and 6, 28.6%, respectively). Atopy was diagnosed in 10 (47.6%) patients. Four (19.0%) had food allergy, 3 (14.3%) had respiratory allergy, and 3 (14.3%) had combined. Linear furrows and circular rings were the most common endoscopic features – 17 (81.0%) and 10 (47.6%), respectively, while papillary elongation, basal zone hyperplasia, and eosinophilic infiltrate were the most common reported histopathological features. Almost all patients received proton pump inhibitors (19, 90.5%). Steroids were used in 18 (85.7%) patients; local steroids in 11 (52.4%), and oral steroids in 7 (33.3%). Out of the 4 (19%) patients with esophageal strictures, 2 (9.5%) required pneumatic dilatation.ConclusionsEosinophilic esophagitis is not uncommon in our community. Clinical and histological parameters point to delayed referral and diagnosis. Increasing awareness of this problem will lead to early diagnosis and will decrease complications.

Detection of Clostridium difficile Infection in Al-Quwayiyah General Hospital, Riyadh, Kingdom of Saudi Arabia

Clostridium difficile infections (CDIs) is considered healthcare-associated infections which cause watery diarrhea to long stayed hospitalized patients and cause increased mortality rate.&#x0D; Aim: Detection of the prevalence and risk factors of C. difficile in Al Quwayiyah General hospital, Riyadh, Kingdom of Saudi Arabia and compairing between GeneXpert® PCR assay and Quikchek complete-enzyme imunoassay QCC, (QCC-EIA) in detection of C. difficile infection and toxicity&#x0D; Materials and Methods: A cross sectional and prospective study was performed for one year started from June 2019 to June 2020. The data collected include demographic, laboratory and clinical data. A total of 104 stool samples were collected from patients presented with diarrhea. GeneXpert® PCR assay and Quikchek complete-enzyme imunoassay QCC (QCC-EIA) were conducted to each stool sample.&#x0D; Results: Only 15(14.4%) of the 104 studied patients had CDI while 89 (85.6%) were non CDI patients, 13 (86.7%) of the CDI patients were males and 2 (13.3%) were females with mean age for CDI cases 61 (±19.9), while non CDI cases involved 55(61.8%) were males and 34 (38.2%) were females with mean age for cases of non CDI, 60 (±18.7) years. Of the CDI and non CDI cases respectively 12 (80%) and 14(15.7%) had fever, 5 (27%) and 6 (6.7%) had vomitting and 7 (46.7%) and 12 (13.5%) of cases had abdominal pain. There was statistical significant difference between patients with fever while no statistical significant difference regarding vomitting and abdominal pain. There was statistical significant difference between patients with peptic ulcers, patients received proton pump inhibitors and patients received broad-spectrum antibiotics, while There was no statistical significant difference between cardiac disease, cerebrovascular disease, diabetes, pulmonary disease, hepatic disease and Renal disease. Gene expert PCR detected 15/104(14.4%) as positive CDI while QCC-EIA detected 21/104 (20.5%) as positive CDI. On comparison between gene expert PCR technique and QCC-EIA the sensitivity of QCC-EIA was 100%, while the specificity was 91%. The Positive Predictive Value was 74%, while the Negative Predictive Value was 100%.&#x0D; Conclusion: The C. difficile infection prevalence rate in the hospital was 14.4%. There was statistical significant difference between patients with peptic ulcers, patients received proton pump inhibitors and patients received broad-spectrum antibiotics. The QCC-EIA can be used as a screening test for the detection of C. difficile toxin in stool samples but should be confirmed with a PCR assay or another confirmatory test Due to its decreased specificity.

Comparison of Immunohistochemistry and Conventional Stains for Helicobacter Pylori Detection in Gastric Biopsies of Patients Receiving Proton Pump Inhibitors

Objective: To evaluate the diagnostic performance of different staining methods for Helicobacter pylori (H. pylori) in patients treated with proton pump inhibitors (PPI) Material and Methods: This is a retrospective study involving 75 gastric biopsies from patients with and without PPI therapy between October 2018 and September 2019. Slides were stained with hematoxylin and eosin (H&amp;E); Giemsa and immunohistochemical staining (IHC) was done using polyclonal anti-H. pylori antibodies. Statistical analysis was performed to determine any association between the results of different staining methods and PPI consumption. Sensitivity, specificity and positive-negative predictive values of H&amp;E and Giemsa stains were calculated. Results: Overall, H. pylori infection was detected in 33.3% of patients using IHC, 26.7% using H&amp;E, and 28.0% via Giemsa staining. A strong correlation was found between PPI consumption and low H. pylori density detected via IHC (p-value=0.015) but not using H&amp;E and Giemsa staining. The sensitivity of H&amp;E and Giemsa was markedly reduced as a result of PPI consumption (57.1% to 18.2% vs. 85.7% to 27.3%, respectively). Conclusion: Identification of H. pylori using IHC in patients treated with PPI was superior to H&amp;E and Giemsa stains. Both H&amp;E and Giemsa stains showed a marked decrease in sensitivity in patients receiving PPI. The results indicate that IHC should be performed in patients with PPI therapy instead of H&amp;E or Giemsa stains, and PPI should be discontinued for at least 14 days before the performance of endoscopy.

Safety and efficacy of fecal microbiota transplantation (FMT) in the management of recurrent clostridioides difficile infection (rCDI) in cancer patients.

e24048 Background: Cancer patients are at a significantly increased risk of rCDI by virtue of a compromised immune function from underlying malignancy, anti-cancer therapy and frequent antibiotic use for opportunistic infections. Furthermore, cancer patients have shown to have a lower response rate to standard oral antibiotics for CDI. Data is limited in regards to the safety and efficacy of FMT in managing rCDI in cancer patients. We aim to describe our experience of the same at a tertiary care cancer center. Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at the MD Anderson Cancer Center 06/2017-01/2020. FMT was performed through colonoscopy with universal donors’ stool. Baseline clinical data were collected and analyzed. Results: Our sample comprises 19 patients of whom 12 had solid tumors and 7 hematological malignancies, most of which were stage 4 at the time of FMT. The mean age was 66.5 years. Most patients received proton pump inhibitor, antibiotics and cancer therapy within 3-6 months of FMT. On average, each patient had 3 episodes of CDI, received 4 courses of antibiotic treatments, and required 4 CDI related hospitalizations within 1 year prior to FMT. Majority of the CDI episodes were managed with a combination of antibiotics. Bezlotoxumab was used in 4 cases. 18 patients received FMT once, while one patient was treated with FMT thrice. Clinical response was seen in 74% patients with a median time of 1 day. 5 patients had refractory CDI including 3 recurrent rCDI, and 2 persistent symptoms. Compared to patients with good response, these refractory cases received more frequent antibiotics following FMT (100% vs 43%, p=0.033). Side effects were mostly mild GI complaints in 15.8% patients with no serious adverse events or mortality related to FMT. Conclusions: Our study shows that FMT is a safe and effective treatment for rCDI in cancer patients and provides rapid resolution of symptoms; Subsequent antibiotic use for the management of cancer related complications can negatively affect the efficacy of FMT. [Table: see text]

No Differences in Gastrointestinal Bleeding Risk among Clopidogrel-, Ticagrelor-, or Prasugrel-Based Dual Antiplatelet Therapy.

The risk for gastrointestinal bleeding from dual antiplatelet therapy (DAPT) with new antiplatelets (prasugrel/ticagrelor) compared to clopidogrel is unclear. Aim: To determine the risk and type of major (gastrointestinal bleeding requiring hospitalization) and minor (anemia and iron deficiency) gastrointestinal events with different types of DAPT. Methods: Retrospective observational cohort study of patients who started DAPT after percutaneous coronary intervention. Follow-up was censored after 12 months of DAPT, when a major gastrointestinal event occurred, or when DAPT was discontinued. Results: Among 1,327 patients (54.03% were treated with clopidogrel-based DAPT, 38.13% with ticagrelor-based DAPT, and 7.84% with prasugrel-based DAPT), 29.5% had at least one gastrointestinal event. Patients taking clopidogrel-DAPT were older, with more comorbidities, and higher gastrointestinal risk compared to those taking other DAPT regimens. Adjusted hazard ratios (HRs) showed no between-group differences in the risk for major (clopidogrel vs. new antiplatelets: HR 0.996; 95% confidence interval 0.497–1.996) and minor (HR 0.920; 0.712–1.189) gastrointestinal events. Most patients received proton pump inhibitors while on DAPT (93.3%) and after withdrawal (83.2%). Conclusion: Prasugrel- or ticagrelor-based DAPT was not associated with increased gastrointestinal bleeding risk when compared to clopidogrel-DAPT. New antiplatelets do not necessarily need to be restricted to patients with low gastrointestinal risk.

Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses

An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied. To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest. A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018. Continuous PPI use during the 2015 to 2016 AGE winter epidemic. The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions. There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older. Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.

Profile of patients admitted in a pulmonology ward and developing Clostridium difficile enterocolitis

Abstract Clostridium difficile is an anaerobic bacterium than can colonise the lower intestine and cause enterocolitis in susceptible patients. Clostridium difficile infection (CDI) is typically a nosocomial infection, favoured by treatment with antibiotics (especially with broad-spectrum drugs), proton pump inhibitors, but also comorbidities, old age and prolonged hospitalisation. Based on the observation that in the past years, the frequency of nosocomial CDI has increased in the Institute of Pulmonology, Bucharest, this retrospective observational study aimed to analyse the characteristics of admitted patients who develop CDI, in order to identify possible particular features and risk factors. Accordingly, medical files from 80 patients admitted from January 2015 to August 2017 were analysed for demographic data, respiratory diagnosis, comorbidities, blood tests, treatments prescribed, time of CDI onset, evolution and outcome. The number of patients studied was 29 in 2015, 16 in 2016 and 35 in 2017, with slight male predominance. Totally, 54 patients (67.5%) had tuberculosis (pulmonary or pleural), 12 had lung cancer, five had respiratory infections, two had chronic obstructive pulmonary disease and seven had other diseases. All patients but nine were receiving antibiotics: tuberculosis drugs, cephalosporins, fluoroquinolones and beta-lactams. About half of the patients received proton pump inhibitors. Most patients had several comorbidities. Mean time since admittance to onset of diarrhoea was 20 days. CDI was treated with metronidazole or vancomycin. The evolution was favourable in 90% of patients, but eight patients (10%) died This study highlights a high frequency of CDI in patients treated for tuberculosis. Due to insufficient data, no epidemiological consideration could be made. Further studies are needed to assess the relationship among tuberculosis, tuberculosis treatment and CDI.

Late esophagogastric anatomic and functional changes after sleeve gastrectomy and its clinical consequences with regards to gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is described as a complication after sleeve gastrectomy. Most studies have used only clinical symptoms or upper gastrointestinal endoscopy for evaluation of reflux after surgery. Manometry, acid reflux tests, and esophageal barium swallow have not been commonly used. The objective of this study is to evaluate the short- and long-term incidence of clinical gastroesophageal reflux, the lower esophageal sphincter (LES) pressure, acid reflux, and endoscopic and radiological changes after sleeve gastrectomy (SG). A total of 315 patients were studied after SG; 248 (78.3%) completed more than 5 years of follow-up and 67 (21.4%) have more than 8 years (range 8-10 years) of follow-up. The preoperative weight was 106+14.1 kg with a mean body mass index 38.4+3.4 kg/m2. Patients with prior GERD were excluded for SG. During the follow-up patients were subjected to clinical, endoscopic, radiological, manometric, and 24-hour pH monitoring and duodenogastric reflux evaluations. Reflux symptoms were observed in 65.1% of patients at late follow-up. Patients without reflux symptoms presented an LES resting pressure of 13.3±4.2 mmHg while patients with reflux symptoms presented an LES resting pressure of 9.8+2.1 mmHg. In patients with reflux symptoms, a positive acid reflux test was observed in 77.5% of patients with a mean DeMeester score of 41.7±2.9 (range 14.1-131.7). During endoscopy, esophagitis was found in 29.4%, hiatal hernia in 5.7%, and Barrett's esophagus was diagnosed in 4.8%. Positive duodenogastric reflux was found in 31.8% of patients and 57.7% of our patients received proton pump inhibitor treatment after SG. Sleeve gastrectomy presents anatomic and functional changes that are associated with increased GERD.

Features of manifestations, treatment and prevention of nsaids – induced gastroduodenopathy in patients of different profile departments

Introduction. Nonsteroidal anti-inflammatory drugs are the most commonly used medicines in medical practice. As literary sources show, they often cause unwanted side-effects. The purpose of our work was to evaluate the frequency, clinical manifestations and morphological features of lesions of the gastroduodenal zone that arise in patients of rheumatologic, neurological profiles and angiosurgery department during the course of treatment with nonsteroidal anti-inflammatory drugs of different groups, to trace the dependence of the frequency of manifestations of the pathology of the stomach and duodenum from simultaneous receiving two nonsteroidal anti-inflammatory drugs and their combination with glucocorticosteroids and anticoagulants. Material and methods. 73 patients who had used NSAIDs for a long time and had endoscopically confirmed medicated gastroduodenopathy. Patients were divided into 3 groups depending on the profile of the department: Group I included - 24 patients of the department of vascular surgery; Group II - 23 patients of the neurological department; Group III - 26 patients with rheumatological profile. Results. Asymptomatic clinical picture of NSAID-gastropathy was found, which did not coincide with the available endoscopic changes in the gastroduodenal tube: in 63% of cases, erosive changes in the mucous membrane were present, and stomach and duodenal ulcers were revealed in 11%. It was also found that in the group of patients receiving proton pump inhibitors, the incidence of gastroduodenopathy was reliably lower (34.2%) than in patients who did not receive them (53.4%). During this study, it was found that the use of selective non-steroidal anti-inflammatory drugs can significantly reduce the probability of developing the pathology of the gastroduodenal zone, compared with non-selective. Conclusions. The course of treatment with nonsteroidal anti-inflammatory drugs should be as short as possible and should be carried out with minimal but effective doses. Parallel prophylactic administration of proton pump inhibitors is appropriate in patients at high risk of developing erosions and ulcers in the background of treatment with these drugs.

Contribution of genetic amplification by PCR for the diagnosis of Helicobacter pylori infection in patients receiving proton pump inhibitors.

Helicobacter pylori detection by standard methods may be altered by proton pump inhibitor (PPI) use. However, some patients cannot or should not interrupt PPI use before undergoing testing for H. pylori. Polymerase chain reaction (PCR) could allow more reliable H. pylori detection even in patients taking PPIs. The aim of our study is to compare the H. pylori infection diagnostic value of histological examination without and with immunohistochemical staining, bacterial culture and PCR, in PPI-treated vs untreated patients. Patients undergoing a gastric endoscopy for upper digestive symptoms were included. Gastric biopsy samples were obtained. The impact of taking PPI on the diagnostic performance of the different methods was studied. PCR results were confirmed by sequencing the glmM gene. A total of 497 patients were included, of whom 192 were H. pylori positive. Fifty-two patients received PPIs during the 14 days preceding the endoscopy while 140 did not. All methods had lower sensitivity than PCR, in all cases (PPI treatment or not). PPI use did not change significantly the methods' sensitivities. The PCR method showed the best performance for the detection of H. pylori in gastric samples, whether or not patients received previous PPI treatment. This diagnosis test could become a new gold-standard test, especially in patients undergoing PPI treatment.

Secular trends in the epidemiology of Clostridium difficile infection (CDI) at a tertiary care hospital in Barcelona, 2006–2015: A prospective observational study

ObjectiveDescribe secular trends in the epidemiology and outcome of Clostridium difficile infection (CDI) at a tertiary hospital. MethodsAll consecutive primary CDI episodes in adults (January 2006–December 2015) were included. CDI was diagnosed on the presence of diarrhoea and a positive stool test for C. difficile toxin A and/or B. To define trends, a time-series analysis was performed using yearly data on demographics, clinical characteristics, management, antimicrobial treatment, and outcome of CDI. Patients were followed-up for three months after the diagnosis. ResultsThere were 724 CDI episodes. Over the period from 2006 to 2015, the incidence rose from 0.18 episodes/1000 admissions to 0.26 episodes (relative rate [RR] 1.43; 95%CI, 1.02–2.00; P = 0.035). Median Charlson comorbidity index increased from 2 (IQR 1–3) to 4 (IQR 2–4) (RR 1.65; 95%CI, 1.12–2.41; P = 0.005). Overall, 80.4% of patients received proton pump inhibitors (PPIs) prior to CDI, and the percentage of PPI discontinuations rose from 2.3% to 20.4% (RR 8.80; 95%CI 1.20–64.36; P = 0.006). Management of non-Clostridium antibiotics also changed: antibiotic withdrawals or switches increased from 4.2% to 29.2% (RR 7.00; 95%CI 1.68–29.15, P = 0.001). Regarding CDI treatment, the percentage of patients treated with metronidazole decreased (88.9% vs 52.6%) (RR 0.59 (0.48–0.73), P < 0.001), whereas the percentage receiving vancomycin increased (1.9% vs 32.6%) (RR 17.62 (2.47–125.49), P < 0.001). The percentages of cures, deaths, and first recurrences did not significantly change over the 10-year period. ConclusionsChanges in CDI management were associated with a stable prognosis (percentage of cures and first recurrences), even though affected patients had a greater number of comorbidities over time.

Risk of small intestinal bacterial overgrowth in patients receiving proton pump inhibitors versus proton pump inhibitors plus prokinetics.

Background and AimIntestinal dysmotility is considered a risk factor for small intestinal bacterial overgrowth (SIBO). Prokinetics improve intestinal motility and are often prescribed with proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) and/or functional dyspepsia. The present study aimed to evaluate the prevalence of SIBO and the orocecal transit time (OCTT) in patients taking PPI compared with those taking PPI plus prokinetics.MethodsThe study is a single‐center, cross‐sectional study. Enrolled patients (with age > 12 years) were divided into two groups: patients taking PPIs for more than 3 months (Group A) and those taking PPIs with prokinetics for more than 3 months (Group B) for various indications. Lactulose breath test (LBT) for OCTT and glucose breath test (GBT) for SIBO were conducted for all patients.ResultsOf the 147 enrolled patients, SIBO was documented in 13.2% patients in Group A versus 1.8% in Group B, P = 0.018. Median OCTT in Group A was 130 (105–160) min compared with 120 (92.5–147.5) min in Group B (P = 0.010). Median OCTT among SIBO‐positive patients was 160 (140–172.5) min compared with SIBO‐negative patients, where it was 120 (103.75–150) min (P = 0.002). The duration and type of PPI used were not associated with the occurrence of SIBO in our study.ConclusionThe use of prokinetics in patients on PPI may reduce the risk of SIBO by enhancing intestinal motility and may reduce SIBO risk associated with long‐term PPI use.

Up in Smoke: Uncovering a Lack of Evidence for Proton Pump Inhibitors as a Source of Tetrahydrocannabinol Immunoassay False Positives.

It is recommended that positives in immunoassay drug screens be followed up with more specific confirmatory testing. The drug package insert for pantoprazole mentions reports of false-positive urine screening tests for tetrahydrocannabinol in patients receiving proton pump inhibitors, but no method details or data are given, referenced, or found in literature searches. Thus, we investigated this using our laboratory's assay. A spiked sample and samples from 32 patients taking a proton pump inhibitor were analyzed using the EMIT II Plus Cannabinoid assay with a 20 ng/mL cutoff. Additionally, we examined urine samples from 50 patients with false-positive or low-positive screens for evidence of a proton pump inhibitor. To determine whether O-desmethyl pantoprazole sulfate, the major metabolite, shares any structural or electrostatic similarity to suggest a basis for cross-reactivity in the immunoassay, we used computational techniques for analyses. Molecular electrostatic potential energy (MEP) maps were calculated for the global minimum conformers, and the maximum common substructure Tanimoto similarity was calculated for the modeled compounds. Neither the spiked sample nor the patient samples were found to screen positive. None of the false-positive or low-positive screens were found to contain a proton pump inhibitor. Computational studies showed very little similarity in shape or electrostatics between the two molecules. We find no supporting evidence of pantoprazole as the cause of false positives in the EMIT II Plus Cannabinoid assay and caution the use of proton pump inhibitors as an explanation for tetrahydrocannabinol immunoassay false positives.

Incidence and costs of achalasia in The Netherlands.

Recent reports show increasing incidence of achalasia in some populations. The aim of this study was to estimate incidence, prevalence, and healthcare costs of achalasia in a large cohort in The Netherlands. Data were obtained from the largest Dutch healthcare insurance company (±4.4million insured). Adult achalasia patients were identified between 2006 and 2014 when having an achalasia diagnosis code registered. A total of 907 achalasia patients were identified and included in our database, along with 9068 control patients (non-achalasia patients), matched by age and gender. The mean incidence over the 9-year period was 2.2 per 100000 persons and the mean prevalence was 15.3 per 100000 persons. Mean age of achalasia patients was 54 (range 18-98)years. Male to female ratio was 1:1. Socio-economic status distribution was similar in achalasia patients and controls. Prior to the diagnosis, 74% of achalasia patients received proton pump inhibitors and 26% received anti-emetic medication. The first year after diagnosis median total direct medical costs of achalasia patients were €2283 (IQR 969-3044) per year. Patients above the 90th percentile of €4717 were significantly older than other patients below the 90th percentile (mean age 63 vs 57); P=.005. In this large study that used a database comprising about 25% of all inhabitants of The Netherlands, it is confirmed that achalasia affects individuals of both genders and all ages. The costs associated with diagnosis and treatment of new cases of achalasia increase with increasing age.