Do dietary interventions exert clinically important effects on the bioavailability of ß-lactam antibiotics? A systematic review with meta-analyses.

BACKGROUND: Managing drug-food interactions may help to achieve the optimal action and safety profile of ß-lactam antibiotics. METHODS: We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 ß-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. RESULTS: Eighteen of 25 ß-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed ß-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). CONCLUSIONS: Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.

Sample Preparation Techniques for Growth-Promoting Agents in Various Mammalian Specimen Preceding MS-Analytics.

The misuse of growth-promoting drugs such as beta-2 agonists and steroids is a known problem in farming and sports competitions. Prior to the analysis of biological samples via liquid chromatography (LC)-mass spectrometry (MS) or gas chromatography (GC)-MS, sufficient sample preparation is required to reliably identify or determine the residues of drugs. In practice, broad screening methods are often used to save time and analyze as many compounds as possible. This review was conceptualized to analyze the literature from 2018 until October 2023 for sample preparation procedures applied to animal specimens before LC- or GC-MS analysis. The animals were either used in farming or sports. In the present review, solid phase extraction (SPE) was observed as the dominant sample clean-up technique for beta-2 agonists and steroids, followed by protein precipitation. For the extraction of beta-2 agonists, mixed-mode cation exchanger-based SPE phases were preferably applied, while for the steroids, various types of SPE materials were reported. Furthermore, dispersive SPE-based QuEChERs were utilized. Combinatory use of SPE and liquid-liquid extraction (LLE) was observed to cover further drug classes in addition to beta-2 agonists in broader screening methods.

Effect of an Antacid (Aluminum Hydroxide/Magnesium Hydroxide/Simethicone) or a Proton Pump Inhibitor (Omeprazole) on the Pharmacokinetics of Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Adult Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label, 3-period, fixed sequence study evaluated the effect of gastric acid-reducing agents, aluminum hydroxide/magnesium hydroxide/simethicone, and omeprazole on the pharmacokinetics (PK) of tebipenem (TBP), the active moiety, following coadministration with immediate release TBP-PI-HBr during fasting. In Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets). In Period 2, subjects received a single oral dose of aluminum hydroxide 800 mg/magnesium hydroxide 800 mg/simethicone 80 mg suspension co-administered with a single dose of TBP-PI-HBr 600 mg. In Period 3, subjects received a single oral dose of omeprazole 40 mg once daily over 5 days, followed by single dose administration of TBP-PI-HBr 600 mg on day 5. In each period, whole blood samples were obtained prior to, and up to 24 h, following TBP-PI-HBr dose administration in order to characterize TBP PK. A 7-day washout was required between periods. Twenty subjects were enrolled and completed the study. Following co-administration of TBP-PI-HBr with either aluminum hydroxide/magnesium hydroxide/simethicone or omeprazole, total TBP exposure (area under the curve [AUC]) was approximately 11% (geometric mean ratio 89.2, 90% confidence interval: 83,2, 95.7) lower, and Cmax was 22% (geometric mean ratio 78.4, 90% confidence interval: 67.9, 90.6) and 43% (geometric mean ratio 56.9, 90% confidence interval: 49.2, 65.8) lower, respectively, compared to administration of TBP-PI-HBr alone. Mean TBP elimination half-life (t1/2) was generally comparable across treatments (range: 1.0 to 1.5 h). Concomitant administration of TBP-PI-HBr with omeprazole or aluminum hydroxide/magnesium hydroxide/simethicone is not expected to impact the efficacy of TBP-PI-HBr, as there is minimal impact on TBP plasma AUC, which is the pharmacodynamic driver of efficacy. Co-administration was generally safe and well tolerated.

Cholera Vaccine: Recommendations of the Advisory Committee on Immunization Practices, 2022.

THIS REPORT SUMMARIZES ALL RECOMMENDATIONS FROM CDC'S ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) FOR THE USE OF LYOPHILIZED CVD 103-HGR VACCINE (CVD 103-HGR) (VAXCHORA, EMERGENT BIOSOLUTIONS, GAITHERSBURG, MD) IN THE UNITED STATES. THE LIVE ATTENUATED ORAL CHOLERA VACCINE IS DERIVED FROM: Vibrio cholerae O1 and is administered in a single dose. Cholera is a toxin-mediated bacterial gastrointestinal illness caused by toxigenic V. cholerae serogroup O1 or, uncommonly, O139. Up to 10% of infections manifest as severe cholera (i.e., cholera gravis), profuse watery diarrhea that can cause severe dehydration and death within hours. Fluid replacement therapy can reduce the fatality rate to <1%. Risk factors for cholera gravis include high dose exposure, blood group O, increased gastric pH (e.g., from antacid therapy), and partial gastrectomy. Cholera is rare in the United States, but cases occur among travelers to countries where cholera is endemic or epidemic and associated with unsafe water and inadequate sanitation. Travelers might be at increased risk for poor outcomes from cholera if they cannot readily access medical services or if they have a medical condition that would be worsened by dehydration, such as cardiovascular or kidney disease. This report describes previously published ACIP recommendations about use of CVD 103-HgR for adults aged 18-64 years and introduces a new recommendation for use in children and adolescents aged 2-17 years. ACIP recommends CVD 103-HgR, the only cholera vaccine licensed for use in the United States, for prevention of cholera among travelers aged 2-64 years to an area with active cholera transmission. Health care providers can use these guidelines to develop the pretravel consultation for persons traveling to areas with active cholera transmission.

Use of food and food-derived products in the treatment of gastritis: A systematic review.

Gastritis is the acute or chronic inflammation of gastric mucosa and is triggered by diverse factors. Treatments used for non-bacterial gastritis include proton pump inhibitors, histamine H2 receptor inhibitors, and antacids, and their use is linked to various side effects. Research on alternative therapeutics using food or food-based products is extensive, mostly in preclinical research. We aimed at documenting the clinical advances in food-based therapies as alternative therapeutics for gastritis. Articles with information on the treatment of gastritis with food or food-based products published until December 1, 2020 were identified through a systematic search in PubMed Medline Database. Additionally, references of retrieved articles were screened for relevant reviews and meta-analyses. Two investigators independently selected and reviewed the titles and abstracts of articles and extracted the study characteristics (PICO framework) and key findings. Dual quality assessment and data extraction were performed. We found 28 clinical studies evaluating garlic, turmeric, red peppers, broccoli sprouts, cranberry juice, honey, oils, and probiotics contained in different foods, such as juices, yogurt, and cheese. The existing literature presents a high risk of bias, and results of the same should be evaluated and replicated with precaution; more rigorous clinical studies are lacking.

A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation.

BACKGROUND: Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage. CASE PRESENTATION: A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20 days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient's sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient's electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case. CONCLUSION: When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient's immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4 + T cells at 100-300/mm3 was highly effective against Cryptosporidium without inducing immunorejection.

Mycobacterium Tuberculosis Infection in AECOPD Combined with Pulmonary Embolism: a Case Report.

BACKGROUND: Mycobacterium tuberculosis belongs to the group of mycobacteria, most of which can cause a delayed hypersensitivity reaction in the body and is a bacterium that causes tuberculosis. Mycobacterium tuberculosis infection often presents with symptoms of tuberculosis toxicity and rarely with respiratory distress. At the same time, chest imaging often shows an ill-defined solid shadow in the apical and posterior segments of the upper lobe and, less frequently, in the dorsal segment of the lower lobe, and less frequently a diffuse nodular shadow. We report a case of AECOPD combined with pulmonary embolism infected with Mycobacterium tuberculosis. METHODS: Bronchoscopy, Next-generation sequencing (NGS). RESULTS: Antacid staining of bronchoalveolar lavage fluid suggested that a small amount of Mycobacterium antacid was visible. NGS was sent for examination and it suggested the presence of Mycobacterium tuberculosis with a sequence number of 5 (reference range ≥ 0). Treatment such as bronchodilation and antituberculosis was given. CONCLUSIONS: In patients with dyspnea, it is crucial to find the causative agent and to promptly improve relevant examinations such as pulmonary arteriography and bronchoscopy, and if necessary, to make a definitive diagnosis by NGS.

Efficacy of antacids for cisplatin-induced gastrointestinal symptoms in the treatment of lung cancer.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) and chemotherapy-associated dyspepsia syndrome (CADS) are frequently appearing adverse effects of cisplatin (CDDP)-containing chemotherapy. Antiemetic guidelines suggest that the administration of antacids such as proton pump inhibitors (PPIs) or histamine type-2 receptor antagonists be considered for CADS, although their efficacy for treating these symptoms remains unknown. This study aimed to reveal whether antacids attenuate gastrointestinal symptoms in CDDP-containing chemotherapy. MATERIALS AND METHODS: In total, 138 patients with lung cancer who received ≥ 75 mg/m2 CDDP-containing regimens were enrolled in this retrospective study. Patients were divided into an antacid group including patients administered PPIs or vonoprazan during all chemotherapy periods and controls without antacid administration. The primary endpoint was the comparison of anorexia incidence during the first cycle of chemotherapy. Secondary endpoints were CINV evaluation and risk factor analysis for the incidence of anorexia using logistic regression analysis. RESULTS: The incidence of anorexia during the first cycle was 54.4% in the control group and 60.3% in the antacid group, without significant differences (p = 0.60). The incidence of nausea was also similar between the groups (p = 1.00). Multivariate analysis suggested that antacid administration was not associated with anorexia. CONCLUSION: Baseline antacid administration does not affect gastrointestinal symptoms associated with CDDP-containing treatment in lung cancer.

Deprescribing antacids after the diagnosis of Clostridioides difficile infection: A single-center observational study.

Overuse of antacids is associated with the development and recurrence of Clostridioides difficile infection (CDI). Discontinuation of unnecessary antacids for CDI management is advocated; however, the clinical pervasiveness on the discontinuation of antacids remains unclear. We conducted a single-center retrospective observational study to determine the rate of antacid discontinuation following CDI diagnosis. Among 51 patients (58 infections; median age 76.5 years, range 69-82; 53.5% women) treated with antimicrobials against C. difficile, 41 had been treated with antacids, and of these, 18 exhibited no indication for antacid administration. However, none had discontinued antacid use. While CDI provides an opportunity for antacid stewardship, it is not implemented in clinical practice. In addition to the efforts of individual clinicians, the dissemination of knowledge of the indications and side effects of antacids, establishment of a multidisciplinary support system, and creation and implementation of a clinical stewardship pathway are necessary to increase the deprescription of antacids in patients with CDI.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Longer-term outcomes of gastroesophageal reflux disease treated with magnetic sphincter augmentation.

Surgical intervention for gastroesophageal reflux disease (GERD) has historically been limited to fundoplication. Magnetic sphincter augmentation (MSA) is a less invasive alternative that was introduced 15 years ago, and it may have a superior side-effect profile. To date, however, there has been just a single published study reporting outcomes in a UK population. This study reports quality-of-life (QOL) outcomes and antacid use in patients undergoing MSA, with a particular focus on postoperative symptoms and those with severe reflux. A single-center cohort study was carried out to assess the QOL outcomes and report long-term safety outcomes in patients undergoing MSA. GERD-health-related quality of life (GERD-HRQL) and Reflux Symptom Index (RSI) scores were collected preoperatively, and immediately postoperatively, at 1-, 2-, 3-, and 5-year follow-up time points. All patients underwent preoperative esophagogastroduodenoscopy, impedance, and manometry. Two hundred and two patients underwent laparoscopic MSA over 9 years. The median preoperative GERD-HRQL score was 31, and the median RSI score was 17. There was a reduction in all scores from preoperative values to each time point, which was sustained at 5-year follow-up; 13% of patients had a preoperative DeMeester score of >50, and their median preoperative GERD-HRQL and RSI scores were 32 and 15.5, respectively. These were reduced to 0 at the most recent follow-up. There was a significant reduction in antacid use at all postoperative time points. Postoperative dilatation was necessary in 7.4% of patients, and the device was removed in 1.4%. Erosion occurred in no patients. MSA is safe and effective at reducing symptom burden and improving QOL scores in patients with both esophageal and laryngopharyngeal symptoms, including those with severe reflux.

A Comparative Analysis of Phytochemicals, Metal Ions, Volatile Metabolites in Heart Wood, Stem Bark and Leaves of Salix alba L. along with in Vitro Antioxidant, Antacid, Antimicrobial Activities for Sake of Environment Conservation by Substitution of Stem Bark With Leaf.

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.

Community-onset Clostridioides difficile infection in south Serbia.

BACKGROUND: Data from the past decade indicates that Clostridioides difficile infection (CDI) is not only a nosocomial infection but is also increasingly recognized as a disease in the community. OBJECTIVE: We aimed to study community-onset (CO) CDI in the various age groups in south Serbia with its clinical characteristics, risk factors and microbiological characterization. METHODS: The study group included 93 patients with CO-CDI (median age 62). The control group consisted of 186 patients with community-onset diarrhea and stool samples negative tested for CDI. RESULTS: Of all CDI cases diagnosed with a community onset, 74.19% had a previous contact with a healthcare facility in the previous 12 weeks, but 34.40% have no record on hospitalization in the previous 12 months. Using a multivariate statistical regression model, the following risk factors for CO-CDI development were found; antacid usage (OR = 0.267, 95%C.I.:0.10-0.291, p < 0.01), chronic kidney disease (OR = 0.234, 95%C.I.:0.10-0.51, p < 0.01) and antibiotic use during the prior 2 months (OR = 0.061, 95%C.I.:0.02-0.17, p < 0.01), especially tetracycline's (OR = 0.146, 95% C.I.:0.07-0.22, p < 0.01) and cephalosporin's (OR = 0.110, 95%C.I.:0.14-0.42, p < 0.01). The most common ribotypes (RTs) detected in patients with CO-CDI were RT001 (32.3%) and RT027 (24.7%). All tested toxin producing C. difficile isolates were sensitive to metronidazole, vancomycin and tigecycline. A high rate of resistance to moxifloxacin (73.11%) and rifampicin (23.65%) was found. CONCLUSION: Patients with CO-CDI had frequently contact with healthcare facility in the previous 12 weeks. Restriction of antacid usage and of high-risk antibiotics in the community may help reduce the incidence of CO-CDI.

The in vitro study of interaction between antacids and anti-diabetic drug sitagliptin in the treatment of type II diabetes.

Hyperglycemia is a long-lasting syndrome that occurs either when the pancreas cannot produce enough insulin, or the body cannot effectively utilize that insulin to regulate blood sugar levels. Non-insulin-dependent hyperglycemia, also known as type II diabetes, causes a common consequence of severe damage to many of the body's organs mainly the blood vessels and nerves. The majority of people around the world are suffering from non-insulin-dependent diabetes. The present work showed a great effort to investigate any possible interaction between antacids and sitagliptin (anti-diabetic drug) in the treatment of type II diabetes with gastrointestinal tract problems. The in vitro studies were carried out in simulated gastric juice pH 2.0 and intestinal pH 7.4 at 37oC. MgCO3, NaHCO3, Mg(OH)2, Al(OH)3 and CaCO3 were used as antacids in these studies. It has been observed that % release of sitagliptin was significantly enhanced in the presence of calcium carbonate and magnesium carbonates.

Comorbidities and co-medications among 28 089 people living with HIV: A nationwide cohort study from 2009 to 2019 in Japan.

OBJECTIVES: Comorbidities are associated with a high burden of disease in people living with HIV (PLWH). The objective was to investigate the prevalence of chronic comorbidities and use of co-medications in PLWH in Japan. METHODS: This study retrospectively analysed clinical information from PLWH receiving antiretroviral therapy (ART) between April 2009 and March 2019. Demographic characteristics, numbers and types of chronic comorbidities, and numbers and types of non-ART co-medications, were described by age groups. The source of data was the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). RESULTS: Overall, 28 089 PLWH (male 91.9%) who used ART were identified. Out of 28 089 PLWH, 81.5% had at least one chronic comorbidity. The numbers of AIDS-defining cancers and non-AIDS-defining cancers in this Japanese cohort were 2432 (8.7%) and 2485 (8.8%), respectively. The cumulative burden of comorbidities including non-AIDS-defining cancer increased with age. Changes in trend between 2009 and 2019 were observed, including a higher proportion of PLWH diagnosed at ≥ 70 years old [2019 (4.7%) vs. 2009 (2.4%)] and a decreasing percentage of patients with AIDS-defining cancers (down from 6.3% to 4.8% between 2009 and 2019). The most common co-medications during the most recent 3-month period were lipid-regulating/anti-atheroma preparations (11.3%), antacids, antiflatulents and anti-ulcerants (9.6%), and agents acting on the renin-angiotensin system (8.1%). The three most common therapeutic categories of co-medications during the study period were antacids, antiflatulents and anti-ulcerants (35.0%), systemic antihistamines (33.7%) and psycholeptics (27.1%). More than 30% of PLWH aged > 40 years used at least one co-medication in a 3-month period, while more than half of PLWH aged > 30 years had at least one co-medication prescribed concomitantly for a total of ≥ 90 days during the study period, and the numbers of co-medications used were greater in the older age groups. CONCLUSIONS: The burden of chronic comorbidities and co-medication were found to be greater in older, as compared to younger patients, among 28 089 PLWH in a nationwide study in Japan. This finding suggests the need to identify elderly PLWH and to appropriately manage their HIV and comorbidities.

Magnesium exposure increases hip fracture risks in patients with chronic kidney disease: a population-based nested case-control study.

This population-based study demonstrates a strong link between Mg-containing antacid exposure and hip fracture risk in nondialysis CKD and dialysis patients. As an Mg-containing antacid, MgO is also commonly used as a stool softener, which can be effortlessly replaced by other laxatives in CKD patients to maintain bone health. PURPOSE: Bone fracture is a severe complication in chronic kidney disease (CKD) patients, leading to disability and reduced survival. In CKD patients, blood magnesium (Mg) concentrations are usually above the normal range due to reduced kidney excretion of Mg. The present study examines the association between Mg-containing antacid exposure and the risk of hip fracture of CKD patients. METHODS: In this nationwide nested case-control study, we enrolled 44,062 CKD patients with hip fracture and 44,062 CKD matched controls, among which the mean age was 77.1 years old, and 87.9% was nondialysis CKD. RESULTS: As compared to non-users, Mg-containing antacid users were significantly more likely to experience hip fracture (adjusted odds ratio (OR) 1.36, 95% CI, 1.32 to 1.41; p < 0.001). Subgroup analysis showed that such risk exists in both nondialysis CKD patients and long-term dialysis patients. In contrast, aluminum or calcium-containing-antacid use did not reveal such association. Next, we examined the influence of Mg-containing antacid dosage on hip fracture risk, the adjusted ORs in the first quartile (Q1), Q2, Q3, and Q4 were 1.20 (95% CI, 1.15 to 1.25; p < 0.001), 1.35 (95% CI, 1.30 to 1.41; p < 0.001), 1.49 (95% CI, 1.43 to 1.56; p < 0.001), and 1.54 (95% CI, 1.47 to 1.61; p < 0.001), respectively, showing that such risk exists regardless of the antacid dosage. A receiver operating characteristic curve analysis demonstrated that the best cutoff value of the exposed Mg dose to discriminate the hip fracture is 532 mEq during the follow-up period. CONCLUSION: This population-based study demonstrates a strong link between Mg-containing antacid exposure and the hip fracture risk in both nondialysis CKD and dialysis patients.

Endoscopic Treatment of Reflux: A Comprehensive Review.

The last decade has seen the rise of multiple novel endoscopic techniques to treat gastroesophageal reflux disease, many of which are efficacious when compared with traditional surgical options and allow relief from long-term dependence on antacid medications. This review will explore the latest endoscopic treatment options for gastroesophageal reflux disease including a description of the technique, review of efficacy and safety, and future directions.

Severe Upper Gastrointestinal Hemorrhage Caused by Reflux Esophagitis.

BACKGROUND: There are few reports about reflux esophagitis (RE) as a cause of severe upper gastrointestinal bleeding (UGIB). AIMS: This study aims to evaluate (1) changes in its prevalence over the last three decades and (2) clinical and endoscopic characteristics and 30-day outcomes among RE patients with and without focal esophageal ulcers (EUs) and stigmata of recent hemorrhage (SRH). METHODS: A retrospective study of prospectively collected data of esophagitis patients hospitalized with severe UGIB between 1992 and 2020. Descriptive analysis and statistical comparisons were performed. RESULTS: Of 114 RE patients, the mean age was 61.1 years and 76.3% were males. 38.6% had prior gastroesophageal reflux disease (GERD) symptoms; overall 36% were on acid suppressants. Over three consecutive decades, the prevalence of RE as a cause of severe UGIB increased significantly from 3.8 to 16.7%. 30-day rebleeding and all-cause mortality rates were 11.4% and 6.1%. RE patients with focal EUs and SRH (n = 23) had worse esophagitis than those with diffuse RE (n = 91) (p = 0.012). There were no differences in 30-day outcomes between RE patients with and without EUs and SRH. CONCLUSIONS: For patients with severe UGIB caused by RE, (1) the prevalence has increased significantly over the past three decades, (2) the reasons for this increase and preventive strategies warrant further study, (3) most patients lacked GERD symptoms and did not take acid suppressants, and (4) those with focal ulcers and SRH had more severe esophagitis and were treated endoscopically.

Potential or contraindicated drug-drug interactions with antiretroviral therapy in real-world settings in Taiwan.

BACKGROUND/PURPOSE: Given the complex metabolic pathway of antiretroviral therapy (ART), polypharmacy may increase the risk of drug-drug interactions (DDIs). Therefore, we investigated the frequency of DDIs during ART exposure to improve medical care for patients with human immunodeficiency virus (HIV). METHODS: This was a nationwide cross-sectional study using claims data from the National Health Insurance in Taiwan in 2016. Potential or contraindicated DDIs with recommended first-line ART (1L-ART) or protease inhibitors (PIs) were identified from the University of Liverpool drug interaction database. Fisher's exact or chi-square test was used to determine the significance of categorical variables. RESULTS: A total of 25,863 HIV-infected individuals were identified. Regarding 1L-ART users, patients with contraindicated DDIs accounted for 1-4%, whereas those with potential DDIs accounted for 15-50%. The most frequently coprescribed medications related to potential DDIs were diclofenac and polyvalent cation-containing antacids. Among PI users, 8-10% of them had contraindicated DDIs while 44-50% of them had potential DDIs. The medications related to potential DDIs with PIs were zolpidem, betamethasone, polyvalent cation-containing antacids, and loperamide. CONCLUSION: Our study showed a low prevalence of contraindicated DDIs in the HIV population; however, more attention should be paid to a high proportion of potential DDIs. Strategies to avoid these DDIs should be implemented if possible. Further research that focuses on the long-term clinical impact of potential DDIs is warranted.

A Multi-Scale Study on Deformation and Failure Process of Metallic Structures in Extreme Environment.

It is a macro-micro model study for defect initiation, growth and crack propagation of metallic truss structure under high engine temperature and pressure conditions during the reentry atmosphere. Till now, the multi-scale simulation methods for these processes are still unclear. We explore the deformation and failure processes from macroscale to nanoscale using the Gas-Kinetic Unified Algorithm (GKUA) and all-atomic, molecular dynamic (MD) simulation method. The behaviors of the dislocations, defect evolution and crack propagation until failure for Aluminum-Magnesium (Al-Mg) alloy are considered with the different temperature background and strain fields. The results of distributions of temperature and strain field in the aerodynamic environment obtained by molecular dynamics simulations are in good agreement with those obtained from the macroscopic Boltzmann method. Compared to the tensile loading, the alloy structure is more sensitive to compression loading. The polycrystalline Al-Mg alloy has higher yield strength with a larger grain size. It is due to the translation of plastic deformation mode from grain boundary (GB) sliding to dislocation slip and the accumulation of dislocation line. Our findings have paved a new way to analyze and predict the metallic structural failure by micro-scale analysis under the aerodynamic thermal extreme environment of the reentry spacecraft on service expiration.