Antibiotic or gastric acid inhibitor use during pregnancy and postpartum depression: Population-based cohort study.

INTRODUCTION: Postpartum depression is one of the most common non-obstetric postnatal complications. As the microbiome (and gut-brain axis) as well as inflammation may be involved in the mechanism, we aimed to assess if antibiotic or gastric acid inhibition use during pregnancy affects the risk of postpartum depression (clinical diagnosis and/or antidepressant use up to 1 year after childbirth). MATERIAL AND METHODS: This population-based cohort study used first singleton pregnancy resulting in a live birth in Sweden from 2006 to 2016. Women with history of depression were excluded. Multivariable logistic regression models were used to assess the impact of antibiotics and gastric acid inhibitors and other risk factors, presented as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Overall, 29% of all 10 666 women with postpartum depression were exposed to antibiotics and 6.2% to gastric acid inhibitors, compared to, respectively, 21% and 3.2% of 613 205 women without postpartum depression. Antibiotic use during pregnancy was associated with postpartum depression (OR 1.43, 95% CI 1.37-1.49), particularly for quinolones and other antibacterials (including nitroimidazole derivatives). Gastric acid inhibition was associated with an even higher risk than antibiotics (OR 2.04, 95% CI 1.88-2.21). Both antibiotics and gastric acid inhibitors suggested higher risk with increased dose in a dose-response analysis. CONCLUSIONS: The use of antibiotics and gastric acid inhibition drugs during pregnancy appeared to be associated with a higher risk of postpartum depression. However, it is important to consider that other predisposing factors could contribute to this increased risk, even after excluding individuals with a history of depression.

Effect of acidic environment on color and translucency of different indirect restorative materials.

PURPOSE: The aim of the current study was to evaluate the effect of simulated gastric acid on the color and translucency of different indirect restorative materials. MATERIALS AND METHODS: A total of 36 disc-shaped samples were cut by using an isomet saw and divided into four equal groups (n = 9) according to the material type: Group Z: translucent zirconia (Ceramill® Zolid ht.+ preshade, Amann Girrbach, Koblach, Austria); Group E: lithium disilicate (IPS e.max CAD, Ivoclar Vivadent AG, Schaan, Liechtenstein); Group C: resin nanoceramic (Cerasmart, GC, Tokyo, Japan); Group P: polyether ether ketone (PEEK) (Bettin Zirconia Dentale Italy) veneered with indirect high impact polymer composite (HIPC) (breCAM HIPC, Bredent GmbH & Co. KG, Germany). The samples were immersed in simulated gastric acid (HCl, pH 1.2) for 96 hours at 37 °C in an incubator. The color change (ΔE00) and translucency (RTP00) were measured every 9.6 hours (one-year clinical simulation) of immersion in simulated gastric acid. RESULTS: For color change (∆E00) and translucency (RTP00) among the tested materials, there was a highly statistically significant difference (P < 0.001) after every year of follow-up. The color change in both Z and G groups was the lowest after 1 year of acid immersion, followed by that in group H, and the highest change in color was recorded in group P. CONCLUSION: High translucent zirconia is recommended in patients who are concerned about esthetic, especially with acidic oral environment.

Polyaspartic Acid-Stabilized CaCO3-Containing In Situ Hydrogel for Protection and Treatment of Gastric Ulcer.

The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.

Milk fat globule membrane: composition, production and its potential as encapsulant for bioactives and probiotics.

Milk fat globule membrane (MFGM) is a complex trilayer structure present in mammalian milk and is mainly composed of phospholipids and proteins (>90%). Many studies revealed MFGM has positive effects on the immune system, brain development, and cognitive function of infants. Probiotics are live microorganisms that have been found to improve mental health and insulin sensitivity, regulate immunity, and prevent allergies. Probiotics are unstable and prone to degradation by environmental, processing, and storage conditions. In this review, the processes used for encapsulation of probiotics particularly the potential of MFGM and its constituents as encapsulating materials for probiotics are described. This study analyzes the importance of MFGM in encapsulating bioactive substances and emphasizes the interaction with probiotics and the gut as well as its resistance to adverse environmental factors in the digestive system when used as a probiotic embedding material. MFGM can enhance the gastric acid resistance and bile resistance of probiotics, mainly manifested in the survival rate of probiotics. Due to the role of digestion, MFGM-coated probiotics can be released in the intestine, and due to the biocompatibility of the membrane, it can promote the binding of probiotics to intestinal epithelial cells, and promote the colonization of some probiotics in the intestine.

Prediction of Omeprazole Pharmacokinetics and its Inhibition on Gastric Acid Secretion in Humans Using Physiologically Based Pharmacokinetic-Pharmacodynamic Model Characterizing CYP2C19 Polymorphisms.

PURPOSE: To develop a whole physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model to describe the pharmacokinetics and anti-gastric acid secretion of omeprazole in CYP2C19 extensive metabolizers (EMs), intermediate metabolizers (IMs), poor metabolizers (PMs) and ultrarapid metabolizers (UMs) following oral or intravenous administration. METHODS: A PBPK/PD model was built using Phoenix WinNolin software. Omeprazole was mainly metabolized by CYP2C19 and CYP3A4 and the CYP2C19 polymorphism was incorporated using in vitro data. We described the PD by using a turn-over model with parameter estimates from dogs and the effect of a meal on the acid secretion was also implemented. The model predictions were compared to 53 sets of clinical data. RESULTS: Predictions of omeprazole plasma concentration (72.2%) and 24 h stomach pH after administration (85%) were within 0.5-2.0-fold of the observed values, indicating that the PBPK-PD model was successfully developed. Sensitivity analysis demonstrated that the contributions of the tested factors to the plasma concentration of omeprazole were Vmax,2C19 ≈ Papp > Vmax,3A4 > Kti, and contributions to its pharmacodynamic were Vmax,2C19 > kome > kms > Papp > Vmax,3A4. The simulations showed that while the initial omeprazole dose in UMs, EMs, and IMs increased 7.5-, 3- and 1.25-fold compared to those of PMs, the therapeutic effect was similar. CONCLUSIONS: The successful establishment of this PBPK-PD model highlights that pharmacokinetic and pharmacodynamic profiles of drugs can be predicted using preclinical data. The PBPK-PD model also provided a feasible alternative to empirical guidance for the recommended doses of omeprazole.

Is use of a long-term proton pump inhibitor or histamine-2 receptor antagonist a risk factor for iron-deficiency anaemia in Taiwan? A neglected clinical drug-drug interaction.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain. OBJECTIVES: The present case-control study employed 2 million longitudinal claims in 2011-2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA). METHODS: The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice. RESULTS: Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94-2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73-2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94-3.70, P < 0.05). CONCLUSIONS: This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.

Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists, 2 kinds of gastric suppressants commonly used for gastroesophageal reflux disease, decrease iron absorption in the gut and thus increase the risk of developing iron-deficiency anaemia (IDA). We constructed a retrospective matched case-control study within the Taiwan National Health Insurance Research Database. The longer period of PPIs/H2 antagonists used, the higher risk of IDA was, with the highest risk in female elderly groups (adjusted odds ratio = 2.68 in females aged ≥ 50). PPI users had a higher risk than H2 antagonist users during the 1-year follow-up. The prescription patterns postdiagnosis of IDA witnessed considerable drops for both groups, with less than a 10th of original users remaining the usages (1.72% and 9.85% taking PPIs and H2 antagonists within 90 days after receiving a diagnosis, respectively). Physicians and pharmacists should be aware of the risk of developing IDA in patients currently undergoing or expected to take long-term gastric acid suppressants.

Proton pump inhibitors and the risk of acquiring a penicillin allergy label.

The negative consequences of having a penicillin allergy label are well established. Penicillin allergy de-labelling improves healthcare outcomes; however, less attention is paid to modifying risk factors leading to penicillin allergy development. In this propensity score-matched retrospective cohort study, we used a de-identified population-based database (TriNetX Research Network) and examined the 30-day risk of acquiring a penicillin allergy label in patients using proton pump inhibitors (PPIs). We demonstrated a higher risk of acquiring a penicillin allergy label among PPI users compared to controls.

Gastric acid challenge of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after polishing and glazing-impact on surface properties.

OBJECTIVES: To investigate the impact of simulated gastric acid on the surface properties of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after certain polishing and glazing procedures. MATERIALS AND METHODS: Four different types of square-shaped specimens (10 × 10 × 2 mm3, n = 13) were manufactured: lithium disilicate-reinforced glass-ceramic milled and polished (LDS-P); milled, polished, and glazed (LDS-PG); milled, glazed, and no polishing (LDS-G); and milled and polished zirconia-reinforced lithium silicate glass-ceramic (ZR-LS). Specimens were immersed in hydrochloride acid (HCl 0.06 M, pH 1.2) to simulate gastric acid irritation and stored in the acid for 96 h in 37 °C. Specimen weight, surface gloss, Vickers surface microhardness and surface roughness (Ra, Rq, with optical profilometer), and surface roughness on nanometer level (Sq, Sal, Sq/Sal, Sdr, Sds with atomic force microscope) were measured before and after the acid immersion. RESULTS: ZR-LS specimens lost significantly more weight after acid immersion (p = 0.001), also surface microhardness of ZR-LS was significantly reduced (p = 0.001). LDS-G and LDS-PG showed significantly lower surface roughness (Sa, Sq) values compared to LDS-P before (p ≤ 0.99) and after (p ≤ 0.99) acid immersion and ZR-LS after acid immersion (p ≤ 0.99). CONCLUSIONS: Gastric acid challenge affects the surface properties of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic. Glazing layer provides lower surface roughness, and the glazed surface tends to smoothen after the gastric acid challenge. CLINICAL RELEVANCE: Surface finish of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic has a clear impact on material's surface properties. Gastric acidic challenge changes surface properties but glazing seems to function as a protective barrier. Nevertheless, also glazing tends to smoothen after heavy gastric acid challenge. Glazing can be highly recommended to all glass-ceramic restorations but especially in patients with gastroesophageal reflux disease (GERD) and eating disorders like bulimia nervosa.

Assessment of the Relationship Between Gastric-Acid Suppressants and the Risk of Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis.

Background: Esophageal cancer is a cancerous tumor that develops in the esophagus. It is the 10th most common cancer and has a low survival rate. Esophageal adenocarcinoma (EAC) is increasing in incidence globally. Those with EAC are affected by Barrett's esophagus metaplasia, which is attributed to genetic predisposition and is more common in men. Studies suggest that gastric acid suppressants, like proton pump inhibitors and histamine-2 receptor antagonists, have anticancer properties and reduce EAC. However, other research has suggested that they are not cancer-protective, and the use of antisecretory drugs is a risk factor for developing EAC. Objective: This systematic review and meta-analysis investigated the properties and risk factors associated with using gastric acid suppressants in patients with EAC. Methods: This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Information from selected articles, including the lead author's name, year of publication, study setting, sample size, and gender, was extracted and recorded into an Excel (Microsoft, Redmond, Washington) form. Statistical data included odds ratio, hazard ratio, and/or risk ratio, with a 95% CI associated with patients with EAC and receiving gastric acid suppressants. Data were compared with individuals not receiving treatment. Publication bias was assessed using Begg's and Egger's tests. Statistical analyzes used Stata 14.0 (Stata LLC, College Station, Texas). Results: The initial electronic literature search retrieved 3761 titles/abstracts. Extensive screening selected 20 articles for analysis. Odds ratios associated with EAC in the individuals using gastric acid suppressants were 0.77 (95% CI, 0.49-1.22; P = 0.274) and 0.67 (95% CI, 0.39-1.29; P = 0.240) for proton pump inhibitors and 1.02 (95% CI, 0.44-2.36; P = 0.967) for histamine-2 receptor antagonists. Conclusions: The results found that gastric acid suppressants do not have a protective role in EAC and are not risk factors. Future studies of confounding variables and risk factors are needed to understand what affects EAC development.

The effects of gastric acid on pediatric restorative materials: SEM analysis.

In this study, we aimed to demonstrate changes in the surface roughness and microhardness of three different restorative materials routinely used in pediatric dentistry (composite, compomer and resin-modified glass ionomer cement (RMCIS)) in response to continuous daily exposure to gastric acid. Twelve samples of each of type of restorative material were prepared. Eleven of the specimens were included in the gastric acid cycle. The microhardness and surface roughness of ten samples were measured before and after the cycle. Another sample included in the cycle was compared with the sample not included in the cycle by scanning electron microscopy (SEM). There was a significant difference between the groups in terms of roughness scores following gastric acid cycle (p = 0.039). RMCIS material possessed the highest roughness value. A significant difference was identified in terms of microhardness levels before and after the gastric acid cycle (p = 0.001). The most significant change was observed in the compomer material. SEM analysis, performed after the gastric acid cycle, revealed that most cracks were identified in RMCIS material; this was followed by compomer and composite materials, respectively. Our analysis indicates that the restorative materials used frequently in pediatric dental procedures, show increased surface roughness and reduced microhardness when exposed to gastric acid.

Effect of simulated gastric acid on aesthetical restorative CAD-CAM materials' microhardness and flexural strength.

Background: Gastric acid, which is among erosive substances, gradually rises to the mouth in individuals with reflux and bulimia nervosa disorders, and this causes various effects on dental restorations. Aim: The objective of this study is in vitro investigation of gastric acid's effect on flexural strength and hardness on aesthetic restorative computer-aided design and computer-aided manufacturing (CAD-CAM) materials. Materials and Methods: For this study, four materials have been used, namely Enamic (Vita), Superfect Zir (Aidite) Zirconia, IPS e.max CAD (Ivoclar Vivadent), and Mark II (Vita). From these four different materials, 24 samples with 14 × 4 × 1 dimensions in rectangular prism form are used, which makes a total of 96 samples. One group was separated as the control group, while the rest was allowed to wait at 37°C, 5 ml gastric acid for 96 hours. Hardness value and flexural strengths were measured as pre-exposure and post-exposure to gastric acid. Results: There is a statistically significant difference between the groups in terms of the amount of decrease in the mean hardness after exposure to gastric acid compared to pre-exposure values (p: 0,000; P < 0,05). There was no statistically significant difference between the groups in terms of the amount of decrease in the post-exposure average flexural strength compared to the pre-exposure value (p: 0.063; P > 0.05). There is a statistically significant difference between the groups in terms of the average flexural strength after exposure to the acid. Conclusions: According to the data obtained, it was concluded that exposure to gastric acid affects the hardness and flexural strength properties of dental restorative ceramic materials.

Vulture Genomes Reveal Molecular Adaptations Underlying Obligate Scavenging and Low Levels of Genetic Diversity.

Obligate scavenging on the dead and decaying animal matter is a rare dietary specialization that in extant vertebrates is restricted to vultures. These birds perform essential ecological services, yet many vulture species have undergone recent steep population declines and are now endangered. To test for molecular adaptations underlying obligate scavenging in vultures, and to assess whether genomic features might have contributed to their population declines, we generated high-quality genomes of the Himalayan and bearded vultures, representing both independent origins of scavenging within the Accipitridae, alongside a sister taxon, the upland buzzard. By comparing our data to published sequences from other birds, we show that the evolution of obligate scavenging in vultures has been accompanied by widespread positive selection acting on genes underlying gastric acid production, and immunity. Moreover, we find evidence of parallel molecular evolution, with amino acid replacements shared among divergent lineages of these scavengers. Our genome-wide screens also reveal that both the Himalayan and bearded vultures exhibit low levels of genetic diversity, equating to around a half of the mean genetic diversity of other bird genomes examined. However, demographic reconstructions indicate that population declines began at around the Last Glacial Maximum, predating the well-documented dramatic declines of the past three decades. Taken together, our genomic analyses imply that vultures harbor unique adaptations for processing carrion, but that modern populations are genetically depauperate and thus especially vulnerable to further genetic erosion through anthropogenic activities.

Importance of Gastric Secretion and the Rapid Gastric Emptying of Ingested Water along the Lesser Curvature ("Magenstraße") in Predicting the In Vivo Performance of Liquid Oral Dosage Forms in the Fed State Using a Modeling and Simulation.

The objective of the present study was to develop an in silico model of the stomach for predicting oral drug absorption in fed humans. We focused on a model capable of simulating dynamic fluid volume changes and included a simulated Magenstraße "stomach road," a route along the lesser curvature that often carries fluids rapidly to assess the gastric emptying of drugs. Two types of model liquid drug formulations, liquid-filled soft gelatin capsules (enzalutamide, cyclosporine, and nifedipine) and oral solutions (levofloxacin and fenfluramine), were used. An in silico model was assembled, and simulations were performed using Stella Professional software. The secretion rate of the gastric juice induced by food ingestion was assessed along with the gastric emptying of the ingested water via the Magenstraße in the fed state. The model for the fed state successfully described the in vivo performance of the model drug formulations. These results clearly indicate the importance of including gastric secretion and the kinetics of Magenstraße when predicting the in vivo performance of dosage forms using an in silico modeling and simulation of fed humans. This simulation model should be further optimized to allow for the different physiological mechanisms following the ingestion of different types of meals, as well as modifications for interindividual and intraindividual variabilities in gastrointestinal physiology in the fed state in the future.

Predictors and timing for the development of symptomatic gastroesophageal reflux disease after successful Helicobactor pylori eradication therapy.

BACKGROUND: Helicobacter pylori (H. pylori) eradication success increases the incidence of erosive esophagitis by normalization of gastric acid secretion. The aim of this study is to clarify predictors and timing for the development of symptomatic gastroesophageal reflux disease (GERD) after successful H. pylori eradication based on long-term follow-up. METHODS: From April 2014 to October 2020, 330 patients with H. pylori infections treated with a standard triple-drug regimen were enrolled, and their records retrospectively reviewed. Development of symptomatic GERD was defined as requiring proton pump inhibitor or vonoprazan therapy to treat symptoms. RESULTS: The mean follow-up period was 2.8 years, and symptomatic GERD developed in 41 (12%) patients during the study period. Overall rates of GERD-symptom free patients at 6 months, 1, and 2 years after eradication were 97%, 93%, and 89%, respectively. We evaluated predictors for the development of symptomatic GERD using a Cox proportional hazards regression model. In multivariate analysis, being a current smoker, having functional dyspepsia, hiatal hernia, and severe gastric atrophy were identified as significant predictive factors. The GERD domain score in the Izumo scale was significantly decreased 1 month after vonoprazan therapy consistent with effective treatment of symptomatic GERD. CONCLUSIONS: The rate of development of symptomatic GERD after successful H. pylori eradication is low over long-term follow-up and is easily controlled by vonoprazan therapy. However, patients with smoking habits, functional dyspepsia, hiatal hernia, or severe gastric atrophy should be followed carefully after eradication.

A comparison of efficacy and safety of potassium-competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and meta-analysis aimed to compare the efficacy and safety of PCAB versus PPI in treating gastric acid-related diseases. METHODS: We searched up to June 5, 2022, for randomized controlled trials of gastric acid-related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment-emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings. RESULTS: Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03-1.14), 1.03 (95% CI 1.00-1.07), and 1.02 (95% CI 1.00-1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H. pylori were significantly higher in Vonoprazan versus PPI first-line treatment (RR 1.13; 95% CI 1.04-1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89-1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSION: Vonoprazan is superior to PPI in first-line H. pylori eradication and erosive esophagitis but non-inferior in other gastric acid-related diseases. Likewise, short-term safety is comparable in both treatment groups.

Utilization trend of gastric acid-suppressing agents in relation to analgesics.

BACKGROUND: Controversies exist about excessive use of gastric acid-suppressing agents or lack of adequate indications, especially when co-prescribed with analgesics for gastroprotection. We aimed to analyze the nationwide trend of gastric acid-suppressing agents and analgesics. METHODS: We obtained nationwide consumption data of analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, others) and gastric acid-suppressing agents (proton pump inhibitors [PPI] and histamine-2 receptor antagonists [H2RAs]) between years of 2014-2018 from IQVIA Turkey. Drug utilization was measured by defined daily dose (DDD)/1000 inhabitants/day (DID) unit. Drug sales data were further used to test the correlation of PPIs and H2RAs to analgesics. RESULTS: During the study period, analgesic utilization increased from 65.7 to 67.4 DID. NSAIDs constituted 82.7%-84.9% of all analgesic utilization. The consumption of NSAIDs increased by 3.1%, and the most commonly consumed analgesic was diclofenac (18.5 ± 1.5 DID), constituting 25.4%-29.0% of all analgesics. PPI utilization was found to regularly raise from 52.1 DID in 2014 to 72.0 DID in 2018 with an overall increment of 38.2%. Use of H2RAs was found to increase from 11.4 DID in 2014 to 14.0 DID in 2018. The physician visit-adjusted utilization of both antirheumatic NSAIDs and non-antirheumatic analgesics showed significantly moderate-strong positive correlations with PPIs (r: 0.63, 0.48-0.76 and r: 0.63, 0.47-0.75, respectively) and H2RAs (r: 0.61, 0.44-0.73 and r: 0.57, 0.41-0.71, respectively). CONCLUSION: The utilization trend exhibited a dramatic increase of the gastric acid-suppressing agents -more pronounced for PPIs, with a modest increase in analgesics. Excessive utilization of PPIs does not seem to imply a tendency toward only NSAID-related gastroprotection.

Effect of erosive challenge with HCl on restorative materials.

OBJECTIVE: Investigate the effect of erosive challenge with hydrochloric acid (HCl) on the surface of five different restorative materials. MATERIAL AND METHODS: Ten plates of five restorative materials (Admira Fusion, Activa BioActive-Restorative, Charisma, Equia Forte HT Fil/EF, Filtek Universal Restorative/FU) were obtained. Half of the plate surfaces was covered with an adhesive tape, creating a control area, and the other side was submitted to the HCl (0.06 M HCl; pH 1.2; at 37 °C; for 30 h). Plates with control and HCl-treated areas were analyzed regarding the surface roughness (Sa), roughness profile (Rv), surface loss (SL), microhardness (MI), and gloss (GL) (n = 10). Surface morphology was analyzed by SEM and chemical elements were identified by EDX (n = 5). Data were evaluated by ANOVA and Tukey's test (α = 0.05). RESULTS: Most materials were not affected by HCl. FU showed the lowest Sa and Rv, and the highest GL after HCl. On the other hand, EF presented the highest Sa, Rv, and SL, and the lowest GL. The MI of materials was not changed after HCl. Topographical and chemical alterations were observed after HCl only for EF. CONCLUSIONS: The composites showed minor surface changes after HCl, which was not observed for the glass ionomer cement (EF). FU presented the best performance regarding the parameters evaluated. CLINICAL RELEVANCE: The effects of erosive challenge with HCl on composites were minimal, while the glass ionomer cements might not be indicated as restorative material for patients with gastroesophageal reflux disease.

Vickers micro-hardness study of the effect of fluoride mouthwash on two types of CAD/CAM ceramic materials erosion.

BACKGROUND: The aim of this study was to evaluate the protective effects of fluoride mouthwash on the surface micro-hardness of two types of CAD/CAM ceramics after exposure to acidic solutions. METHODS: 40 samples (5 × 5 × 3 mm3) were prepared from two different ceramics: Vitabloc Mark II CAD, and IPS e.max CAD. The samples were randomly divided into 5 groups in each ceramic (n = 8) immersed in different solutions: Gs: saliva: GGA: gastric acid, GAA: acetic acid, GFGA: sodium fluoride + gastric acid, GFAA: sodium fluoride + acetic acid. The microhardness of samples was measured before and after immersion in different solutions by Vickers microhardness tester. By subtracting the microhardness values after and before immersion, the microhardness changes of the samples were obtained. Data were analyzed by Two-way analysis of variance, one-way analysis of variance, and Tukey test (α = 0.05). RESULTS: Immersion in different solutions reduced the microhardness. Microhardness loss was significantly affected in G FAA and G FGA groups in both types of ceramics (P < 0.05). For Vitabloc Mark II groups, the microhardness loss was significantly higher in GFAA and GFGA compared to IPS e.max CAD P < 0.001). CONCLUSION: Fluoride mouthwash in conjunction with acidic solutions may adversely affect microhardness of Vitabloc Mark II CAD, and IPS e.max CAD that may consequently compromise the clinical service. Vitabloc Mark II CAD was significantly more affected than IPS e.max CAD.

Pre-Endoscopy Use of Proton Pump Inhibitor Intravenous Bolus Dosing in Hemodynamically Stable Patients With Suspected Upper Gastrointestinal Bleeding: Results of a Pharmacist-Managed Hospital Protocol to Reduce Continuous Infusion Pantoprazole Use.

Background: Guidelines for acute upper gastrointestinal bleeding (UGIB) recommend use of proton pump inhibitors (PPI) administered by continuous IV infusion (CI). Although data suggest comparable outcomes with CI and IV push (IVP) dosing post-endoscopy, there are limited data to support IVP PPI as the pre-endoscopy regimen. Objective: To evaluate the impact of a pharmacist-managed protocol for reducing PPI CIs and substitution of PPI IVP dosing in hemodynamically stable patients with suspected acute upper gastrointestinal bleeding (UGIB) prior to endoscopic intervention. Design, Setting, and Participants: Retrospective study; Tertiary-care community teaching hospital; Hemodynamically stable adults with confirmed or suspected UGIB. Hemodynamic stability was defined as a systolic blood pressure >90 mmHg, heart rate <100 beats, mean arterial pressure >65 mmHg, and no requirement for vasopressors. Intervention: All iterations of treatment recommendations encouraged an initial pantoprazole 80 mg IVP dose. In the pre-intervention group, patients were then treated at the at the provider's discretion with the majority receiving CI pantoprazole. After implementation of the original protocol (Phase I), all hemodynamically stable patients were allowed 1 bag of CI pantoprazole (80 mg infused over 10 hours) before being transitioned by the pharmacist to pantoprazole 40 mg IVP every 12 hours. After internal analysis, the protocol was revised to allow patients to be immediately transitioned to IVP dosing without an initial CI (Phase II). Main Outcome: Incidence of continued bleeding or re-bleeding within 7 days of initial PPI dose. Results: A total of 325 patients were included across all 3 study phases. The median number of CI bags per patient was reduced from 4 pre-intervention, to 1.5 in phase I, and to 0 in phase II (P < .001). The primary endpoint of continued bleeding or re-bleeding within 7 days was similar across all 3 groups (5.0% vs 6.5% vs 5.2%, P = .92). Mean intravenous pantoprazole costs were reduced by $21.73/patient. Conclusions: Movement toward preferential use of IVP PPI prior to endoscopy for hemodynamically stable patients with confirmed or suspected UGIBs resulted in similar rates of continued bleeding or re-bleeding and generated modest cost savings. These findings warrant further investigation.

The impact of a 1-hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure.

Co-treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH-dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our study, we investigated whether a 1-hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady-state pazopanib trough concentration (Cmin ) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food. All patients were advised to take GAS 1 hour after pazopanib. Patients were grouped based on the use of GAS and the geometric (GM) Cmin levels were compared between groups for each dose regimen. Additionally, the percentage of patients with exposure below the target threshold of 20.5 mg/L and the effect of the type of PPI was explored. The GM Cmin levels were lower in GAS users vs non-GAS users for both the 800 and 600 mg cohorts (23.7 mg/L [95% confidence interval [CI]: 21.1-26.7] vs 28.2 mg/L [95% CI: 25.9-30.5], P = .015 and 26.0 mg/L [95% CI: 22.4-30.3] vs 33.5 mg/L [95% CI: 30.3-37.1], P = .006). Subtherapeutic exposure was more prevalent in GAS users vs non-GAS users (33.3% vs 19.5% and 29.6% vs 14%). Sub-analysis showed lower GM pazopanib Cmin in patients who received omeprazole, while minimal difference was observed in those receiving pantoprazole compared to non-users. Our research showed that a 1-hour time interval between intake of pazopanib and GAS did not mitigate the negative effect of GAS on pazopanib exposure and may hamper pazopanib efficacy.