Effect of Antacids on the Survival of Patients With Metastatic Urothelial Carcinoma Treated With Pembrolizumab.

INTRODUCTION: Concomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab. PATIENTS AND METHODS: This retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan-Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes. RESULTS: Overall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan-Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs. CONCLUSION: PPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids.

Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses.

BACKGROUND AND OBJECTIVE: Managing drug-food interactions is essential for optimizing the effectiveness and safety profile of quinolones. Following PRISMA guidelines, we systematically reviewed the influence of dietary interventions on the bioavailability of 22 quinolones. METHODS: All studies describing or investigating the impact of food, beverages, antacids, and mineral supplements on pharmacokinetic parameters or pharmacokinetic/pharmacodynamic indices of orally taken quinolones were considered for inclusion. We excluded reviews, in vitro and in silico studies, studies performed on animals, and those involving alcohol. We performed the search in Medline (via PubMed), Embase, and Cochrane Library, covering reports from database inception to December 2022. We used the following tools to assess the risk of bias: version 2 of the Cochrane risk-of-bias tool for parallel trials, the Cochrane risk-of-bias tool for cross-over studies, and the NIH quality assessment tool for before-after studies. We performed quantitative analyses for each quinolone if two or more food-effect studies with specified and comparable study designs were available. If meta-analyses were not applicable, we qualitatively summarized the results. RESULTS: We included 109 studies from 101 reports. Meta-analyses were conducted for 12 antibiotics and qualitative synthesis was employed for the remaining drugs. Of the studies, 60.5% were open-label, cross-over, as recommended by FDA. We judged 46% of studies as having a high risk of bias and only 4% of having a low risk of bias. Among 19 quinolones with available food impact data, 14 (74%) had potentially clinically important interactions. For nalidixic acid, oxolinic acid, and tosufloxacin, food exerted a high positive impact on bioavailability (AUC or Cmax increased by > 45%), whereas, for all the remaining drugs, postprandial absorption was lower. The most significant negative influence of food (AUC or Cmax decreased by > 40%) occurred for delafloxacin capsules and norfloxacin, whereas the moderate influence (AUC or Cmax decreased by 30-40%) occurred for nemonoxacin and rufloxacin. All 14 analysed quinolones showed a substantial reduction in bioavailability when co-administered with antacids and mineral supplements, except for calcium preparations. The impact of beverages was evaluated for 10 quinolones, with 50% experiencing significantly reduced absorption in the presence of milk (the highest negative impact for ciprofloxacin). Moreover, both ciprofloxacin and levofloxacin demonstrated compromised bioavailability when consumed with orange juice, particularly calcium-fortified. DISCUSSION: Several factors may influence interactions, including the physicochemical characteristics of quinolones, the type of intervention, drug formulation, and the patient's health status. We assessed the quality of evidence as low due to the poor actuality of included studies, their methodological diversity, and uneven data availability for individual drugs.

Effect of Food, Crushing of Tablets, and Antacid Coadministration on Maribavir Pharmacokinetics in Healthy Adult Participants: Results From 2 Phase 1, Open-Label, Randomized, Crossover Studies.

The effect of food composition, tablet crushing, and antacid coadministration on maribavir pharmacokinetics was assessed in 2 Phase 1 studies in healthy adults. In the first, a single maribavir 400-mg dose was administered under fasting conditions, with a low-fat/low-calorie or a high-fat/high-calorie meal. In the second, a single maribavir 100-mg dose was administered under fasting conditions, as a crushed tablet, or as a whole tablet alone or with an antacid. The 90% confidence intervals of the geometric mean ratios were within 80%-125% for area under the concentration-time curve (AUC), but not for maximum plasma concentration (Cmax) for low-fat/low-calorie and high-fat/high-calorie meals versus fasting or for whole tablet with antacid versus whole tablet alone. The 90% confidence intervals of the geometric mean ratios for AUC and Cmax were within 80%-125% for crushed versus whole tablet. Maribavir median time to Cmax value in plasma under fed conditions was delayed versus fasting conditions, but there was no statistical difference for crushed versus whole tablet or with versus without antacid. As the antiviral efficacy of maribavir is driven by AUC but not Cmax, findings suggest that maribavir can be administered with food or antacids or as a crushed tablet.

Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management: Delphi consensus study.

BACKGROUND: Gastro-esophageal reflux disease (GERD) may affect the upper digestive tract; up to 20% of population in Western nations are affected by GERD. Antacids, histamine H2-receptor antagonists, and Proton Pump Inhibitors (PPIs) are considered the referring medications for GERD. Nevertheless, PPIs must be managed carefully because their use, especially chronic, could be linked with some adverse effects. An effective and safe alternative pharmacological tool for GERD is needed. After the identification of potentially new medications to flank PPIs, it is mandatory to revise and improve good clinical practices even through a consensus process. AIM: To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method. METHODS: The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel, subject of the consensus, is the basic prerequisite for the consensus itself. A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD. The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations: Gastroenterology, otolaryngology, geriatrics, and general medicine. A scientific committee analyzed the literature, determined areas that required investigation (in agreement with the multiple-choice questionnaire results), and identified two topics of interest: (1) GERD disease; and (2) GERD treatment. Statements for each of these topics were then formulated and validated. The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform. RESULTS: According to their routinary GERD practice and current clinical evidence, the panel members provided feedback to each questionnaire statement. The experts evaluated 15 statements and reached consensus on all 15. The statements regarding the GERD disease showed high levels of agreement, with consensus ranging from 70% to 92%. The statements regarding the GERD treatment also showed very high levels of agreement, with consensus ranging from 90% to 100%. This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management, such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel. The consensus was unanimous among the physicians with different specializations, underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management. The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable (reducing PPIs administration to as-needed use), should be considered. CONCLUSION: Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

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.

A rapid-floating natural polysaccharide gel-raft with double-effect for the treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal condition characterized by regurgitating stomach contents into the esophagus, causing mucosal damage or erosion. Clinical physical protection treatment mainly relies on the use of floating rafts. Bletilla striata (BS) is widely regarded as the first-choice drug for treating digestive tract injuries in Chinese Medicine. The rapid-floating gel-raft (B-R) was prepared via a one-step swelling method using natural BS polysaccharide and glyceryl monooleate. Panax notoginseng saponins (PNS) were loaded to further prepare P/B-R according to clinical experience. Possessing hydrophobic dense, stratified porous structure and stable rheological properties, an outperforming floating performance of P/B-R was proven compared with Gaviscon® (alginate-antacid formulation) in vitro. In vivo imaging results showed that P/B-R can retain and adhere to the gastric mucosa of rats for up to 90 min, protecting and repairing the mucosa. Besides physical protection in situ, the systemic effects of antioxidant and anti-inflammatory actions for treating GERD were achieved through the intestinal release of PNS. Acid-labile PNS was protected by P/B-R against gastric acid, attaining the desired release and permeability. A significantly effective mucosa injury protective effect of P/B-R was found in ethanol-induced gastric damage model on rats. Moreover, P/B-R exhibits excellent biosafety at the cellular level.

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.

Development and evaluation of anti-reflux functional-oral suspension raft composed of sodium alginate-mung bean protein complex.

This study aimed to develop a sodium alginate (Na alginate) and mung bean protein (MBP) raft complex to improve gastric reflux symptoms. Na alginate and MBP complexes with different ratios (1:1, 2:1, and 3:1, respectively) were used for raft formulations through a wet Maillard reaction. Structural properties of raft strength, reflux resistance, intrinsic fluorescence emission spectroscopy, and Fourier transform infrared spectroscopy (FTIR) were investigated for rafts. The suspension 1:1 Na alginate/MBP with 0 h Maillard reaction time exhibited the lowest sedimentation volume among the suspensions. In contrast, 3:1 Na alginate/MBP with 6 h Maillard reaction time showed the highest sedimentation volume. Based on the results, the 3:1 Na alginate/MBP rafts had the best results, and the results were within acceptable limits. Functional properties, including antioxidant properties, the Helicobacter pylori inhibition assay, the pancreatic lipase inhibition assay, and angiotensin-converting enzyme (ACE) inhibition, were investigated for rafts. The Na alginate/MBP raft has similar characteristics to Gaviscon syrup and can be used for obesity, Helicobacter pylori infection, high blood pressure, and gastric reflux.

Comparative study of the efficacy and safety of Abexol (suspension versus tablets) in patients with gastrointestinal symptoms.

BACKGROUND/AIMS: Abexol is a mixture of primary aliphatic alcohols purified from beeswax (Apis mellifera), that produces anti-inflammatory, antioxidant and gastroprotective effects, as well as it is safe and well tolerated. To investigate and compare the efficacy and safety of Abexol (suspension versus tablets) in patients with gastrointestinal symptoms. METHODS: Monocentric study, open-label, randomized design, with two parallel groups receiving Abexol tablets (150 mg/d) or Abexol suspension (75 mg/d) for 8 weeks. Primary efficacy variable (significant improvement in the total score of Gastrointestinal Symptom Rating Scale [GSRS]). Significant reduction in the intensity of the gastrointestinal-symptoms and the reduction in the consumption of antacids are considered secondary efficacy variable. Short form-36 (SF-36) quality of life questiongenonaire was evaluated as collateral variable. Data were analyzed as per intention to treat. RESULTS: A significantly decrease in the overall score of the survey was observed with respect to the baseline level (p < 0.001) of 81.4% in the Abexol suspension group and 77.9% in the Abexol tablets group. At the end of the trial, most gastrointestinal- symptoms disappeared or reduced significantly. The frequency of consumption of neutralizing antacids was low. The significantly improvement in the perception of the state of health obtained in the Abexol is in correspondence with the improvement achieved in some of the components evaluate in the SF-36 questionnaire. Both treatments were safe and well tolerated. CONCLUSION: Abexol suspension showed efficacy and safety similar to Abexol tablets in patients with gastrointestinal symptoms, but using half the dose.

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.

Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study.

Background: Treatment with proton pump inhibitors (PPIs) and antacids affects the gastrointestinal absorption of levothyroxine sodium (LT4) tablets. Patients with hypothyroidism taking LT4 and PPIs or antacids, thus, require appropriate monitoring. The objective of this study was to determine whether a soft gelatin capsule of LT4 (Tirosint®) would obviate the effect of PPIs on LT4 absorption. The objective was achieved by assessing the effects of a switch from a conventional LT4 tablet form to the same dose as soft capsules in thyroidectomized patients on treatment with LT4 and PPIs. Methods: Patients with history of hypothyroidism due to total thyroidectomy on stable treatment with LT4 tablets, and with gastrointestinal disease treated with PPIs, were switched to a 12-week treatment with Tirosint at the same dose of the LT4 tablets, while maintaining treatment with PPIs. Serum thyrotropin (TSH) levels were the primary endpoint of the study. Secondary efficacy endpoints were: serum levels of free thyroxine (fT4), total thyroxine (TT4), free triiodothyronine (fT3), total triiodothyronine (TT3), creatine-phosphokinase (CPK), sex-hormone binding globulin, ferritin, angiotensin converting enzyme, and a lipid panel. Results: Forty-seven patients (36 females and 11 males, mean age 55.4 years) were enrolled and 45 of them completed the study (2 patients withdrew consent). During treatment with Tirosint, mean TSH levels demonstrated a statistically significant decrease (mean changes from baseline: -0.32 mIU/L at week 6 and -0.68 mIU/L at week 12) and concomitant increases in thyroid hormone (TH) levels from baseline to week 12, which were statistically significant for fT3 and TT3 (mean changes from baseline: 0.26 pmol/L and 0.10 nmol/L, respectively). Significant decreases of serum low-density lipoprotein, total cholesterol, and CPK levels were observed at week 12. No signs/symptoms arose during the study that could be specifically correlated to either hypo- or hyperthyroidism. Conclusions: In thyroidectomized patients taking PPIs and replacement LT4, a switch from conventional LT4 tablets to LT4 soft capsules at the same dose was associated with a significant decrease in TSH and increase in TH, indicating that LT4 absorption may be less affected by PPIs when given in the form of soft capsules. Clinical Trial Registration: NCT03094416.

Nonprescription Heartburn Medications for Adults.

This JAMA Patient Page describes the types of nonprescription heartburn medications: antacids, histamine 2 blockers, and proton pump inhibitors.

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.

Simultaneously Enhanced Thermostability and Catalytic Activity of Xylanase from Streptomyces rameus L2001 by Rigidifying Flexible Regions in Loop Regions of the N-Terminus.

The GH11 xylanase XynA from Streptomyces rameus L2001 has favorable hydrolytic properties. However, its poor thermal stability hinders its widespread application in industry. In this study, mutants Mut1 and Mut2 were constructed by rationally combining the mutations 11YHDGYF16, 23AP24/23SP24, and 32GP33. The residual enzyme activity of these combinational mutants was more than 85% when incubated at 80 and 90 °C for 12 h, and thus are the most thermotolerant xylanases known to date. The reduced flexibility of the N-terminus, increased overall rigidity, as well as the surface net charge of Mut1 and Mut2 may be partially responsible for the improved thermal stability. In addition, the specific activity and catalytic efficiency of Mut1 and Mut2 were improved compared with those of wild-type XynA. The broader catalytic cleft and enhanced flexibility of the "thumb" of Mut1 and Mut2 may be partially responsible for the improved specific activity and catalytic efficiency.

Liquid-like Oral Sustained-Release System Based on Acid-Sensitive in situ Hydrogel for Alleviate Gastrointestinal Side Effects of Indobufen.

Commonly, most oral non-steroidal anti-inflammatory drugs (NSAIDs) have known gastric adverse reactions due to their long-term and high dose administration. In this study, a novel liquid sustained-release system based on multiple-unit in situ hydrogel beads was designed to address this issue. The system is composed of sodium alginate (SA), gellan gum (GG), zinc oxide (ZnO), and magnesium oxide (MgO). Furthermore, indobufen was loaded into the system to evaluate its gastric mucosal protection effect. This effect can be attributed to the topical antacid, pepsin inhibition, and sustained drug release properties of the system. It was proven that the stored solid gel system could undergo a "solid to liquid" transition after shaking. Once swallowed, the liquid gel could disperse well in the stomach as hydrogel beads. Then, the "liquid to solid" gelation occurred from the exterior to interior of each multiple-unit gel bead, triggered by the release of Zn2+ and Mg2+ from neutralization reactions. The formed gel demonstrated mild antacid effect that lasted for 3 hours and 66.3% pepsin inhibition in vivo. Moreover, the rats treated with the indobufen gel system showed a drug plasma concentration versus time curve with less fluctuation compared to the rats treated with the marketed preparation (YinDuo®) group. The gel system also exhibited an extended Tmax (6.50 hours) and reduced Cmax (52.87 µg/mL). Additionally, the gastric mucosal protection of the gel system was verified using three types of peptic gastric ulcer models. These findings suggested that this multiple-unit in situ gel could be a potential oral liquid sustained release delivery system for NSAIDs.

A Review of Histamine-2 Receptor Antagonist and Proton Pump Inhibitor Therapy for Gastroesophageal Reflux Disease in Neonates and Infants.

Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are commonly used medications in neonates and infants for the treatment of gastroesophageal reflux disease (GERD), especially in neonatal intensive care units (NICUs). A literature review was conducted to evaluate the efficacy and safety of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) in preterm neonates, term neonates, and infants. A total of 27 studies were included in this review. Antacid medications in studies have consistently shown positive pharmacodynamic effects, including increasing gastric pH, reducing the reflux index, and reducing the number of acidic reflux events. The benefit found in placebo-controlled trials are limited exclusively to these surrogate outcomes. The actual clinically salient outcomes which H2RAs and PPIs are used for, such as reduction in GERD symptoms, especially irritability and improved feed tolerance and weight gain, have consistently shown no clinical benefit. H2RAs and PPIs appear to be extremely well tolerated by the neonatal and infant populations, which would mimic our experience with these medications in our unit. The available data from large, retrospective cohort and case-control studies paint a much more concerning picture regarding the potential for an increased risk in the development of allergies, anaphylactic reactions, necrotizing enterocolitis (NEC), other nosocomial infections, and lower respiratory tract infections. Given the risks associated with and lack of clinical effectiveness of both H2RAs and PPIs, use of these medications should be limited to specific clinical situations. Further studies are required to determine whether antacid pharmacologic therapy might benefit certain neonates and infants, such as those with complex medical issues.

Validation of a Rapid Microbiological Method for the Detection and Quantification of the Burkholderia cepacia Complex in an Antacid Oral Suspension.

BACKGROUND: Despite the broad adoption of Soleris® technology in the food industry as semiquantitative method, it is almost completely unexplored in the pharmaceutical industry as a quantitative method for quantification of Burkholderia cepacia complex (Bcc). OBJECTIVE: The efficacy of an automated growth-based system for a quantitative determination of the Bcc in an antacid oral suspension was studied. The main purpose of this validation study was to prove that the alternative method's entire performance is not inferior to the conventional method for a quantitative determination of Bcc. METHOD: The antacid oral suspension's preservatives were neutralized, leading to the Burkholderia complex's recovery by means of the alternative method and the reference method. A calibration curve was generated for each strain by plotting DTs relative to the corresponding log CFU values. An equivalence of results was done through the construction of calibration curves that allowed the establishment of numerically equivalent results between the enumeration data from the reference method and the alternative method. RESULTS: Thus following the guidelines of USP, essential validation parameters were shown, such as equivalence of results (CC >0.95), linearity (R2 >0.9025), accuracy (% recovery >70%), operating range, precision and ruggedness (DS <5 and CV <35%), specificity (inclusivity and exclusivity), limit of detection (LOD), and limit of quantification (LOQ). CONCLUSIONS: It was shown that all the test results obtained from the alternative method were in statistical agreement with the standard method. Thus this new technology was found to meet all the validation criteria needed to be considered as an alternative method for the quantification of the Burkholderia complex in the antacid oral suspension tested. HIGHLIGHTS: As outlined in USP chapter <1223> and demonstrated in this research the implementation of alternative methods can offer benefits in execution and automation while improving accuracy, sensitivity, and precision and can reduce the microbiological process time compared to the traditional ones.

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.

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.

Performance Equivalence and Validation of a Rapid Microbiological Method for Detection and Quantification of Yeast and Mold in an Antacid Oral Suspension.

Alternative and rapid microbiological methods can be effective replacements for more traditional plating approaches for ensuring quality and safety in the pharmaceutical industry. This article compares the efficacy of the Soleris automated method and the traditional plate-count method for the quantitative detection of yeasts and molds at three different microbial bioburden levels. Validation testing was carried out using an antacid oral suspension (aluminum hydroxide 4% + magnesium hydroxide 4% + simethicone 0.4%). Equivalence of data between detection time and colony-forming units was established for both the alternative and the conventional methodologies. Using probability of detection, linear Poisson regression, Fisher's test, and multifactorial analysis of variance (ANOVA), all results from the rapid method were shown to be in statistical agreement with the those of the reference plating procedures. The limits of detection and quantification were statistically similar for both methods (Fisher's exact test, P > 0.05), showing that the alternative method is not inferior in performance to the reference method. Essential validation parameters such as precision (standard deviation <5, coefficient of variance <35%), accuracy (>70%), linearity (R2 >0.9025), ruggedness (ANOVA, P < 0.05), operative range, and specificity were determined. It was shown that all the test results obtained using the alternative method were in statistical agreement with the those of the standard plate-count method. Thus, this new technology was found to meet all the validation criteria needed to be considered as an alternative method for yeast and mold quantification in the antacid oral suspension tested. However, taking into account that the present validation was carried out utilizing A. brasiliensis and C. albicans as suitable models for yeasts and molds and with an antacid oral suspension as a pharmaceutical matrix, further investigation will be required to qualify Soleris technology for other environmental isolates and recovery of these isolates from production batches.