Alginate raft-forming oral suspension sugar free

Phage therapy has enormous potential in combating bacterial resistance in food animals. However, its application via the oral route remains limited due to challenges associated with the gastrointestinal tract (GIT) environment and a lack of rigorous clinical trial evidence. Therefore, we systematically searched in Google Scholar, PubMed, Scopus, and Web of Science databases following PRISMA guidelines and finally identified 111 articles on oral phage therapy in food animals from where we summarized the key physiological and chemical factors of the gut environment hindering the effectiveness of oral phage therapy (OPT), examined the methods used to evaluate phage stability in the GI environment, and highlighted potential strategies to mitigate these challenges. In addition, we performed quantitative analysis to visualize in vitro pH and thermal stability patterns of phages targeting bacteria isolated from food animals and variability in buffer and incubation period across stability studies. The GIT consists of several anatomically and functionally distinct segments, where complex interactions occur among digestive enzymes, gastric acids, electrolytes, commensal microbiota, and mucosal immune components. The acidic pH of the stomach is a major barrier to successful oral phage delivery. According to our analysis of pH stability testing data from the reviewed studies, most phages targeting antimicrobial-resistant bacteria in food animals remained stable at pH 5-9 and inactivated under highly acidic (pH ≤ 2) or highly alkaline (pH ≥ 11) conditions. In addition, phages are susceptible to high temperatures (above 60 °C), digestive enzymes (e.g., pepsin, trypsin, lipases), bile salts, and host immune responses. Several in vitro laboratory techniques are available to assess phage stability under simulated GI conditions, but variations occur in the assessment protocols. Microencapsulation using alginate and chitosan has been used to protect phages from the adverse GI environment. Additionally, enteric-coated capsules, antacids, co-encapsulation with acid-neutralizing agents, consumption of alkaline water, and daily phage administration are suggested to improve phage survival and efficacy. For the successful clinical implementation of OPT in food animals, future research should focus on elucidating the molecular and physicochemical determinants of phage stability, understanding the humoral immune response to OPT, standardizing laboratory protocol for assessing phage viability, improving the scalability of encapsulation methods, and exploring other potential delivery techniques.

Abstract licence: CC BY

IntroductionPersistent throat symptoms (PTS) are indicators for over 60 000 new patient referrals to NHS secondary care annually. PTS have been attributed to manifestation of gastro-oesophageal reflux disease (GORD) with the hypothesis that gastric refluxate damages and irritates the mucosa of the upper aerodigestive tract. Symptoms of PTS and GORD are commonly treated with proton pump inhibitors (PPIs) or alginates are often, incorrectly, advocated. The Trial of PPIs in Throat Symptoms trial definitively demonstrated that lansoprazole is no more effective than placebo in treating symptoms of PTS, indicating that empirical PPI treatment for PTS should be discouraged. The impact of this is an anticipated increase in prescriptions of alginates for PTS, however, there is a lack of evidence of the efficacy of alginates in treating this condition. Trial of alginates in throat symptoms aims to compare symptomatic response of the symptoms of PTS in liquid alginate (Gaviscon Advance) in comparison to a near matched placebo over an 8-week period to provide definitive evidence of the use of alginates in treating PTS.Methods and analysisThis is a multicentre, pragmatic, double blind, parallel, randomised controlled trial. 250 adults with PTS will be recruited from NHS secondary care sites and randomised to either liquid alginate (Gaviscon Advance) or near matched placebo in a 1:1 ratio. The primary objective is to compare the symptomatic response in patients with PTS to liquid alginate (Gaviscon Advance) compared with placebo using the outcome measure of total Reflux Symptom Index questionnaire score at 8 weeks.Ethics and disseminationFavourable ethical opinion was received from the East Midlands-Leicester South Research Ethics Committee (reference: 22/EM/0205). All participants will provide informed consent prior to any trial specific activity taking place. Results will be disseminated in peer reviewed publications, at national and international conferences, in peer reviewed journals and to participants and the public (using lay language).Trial registration numberISRCTN13949559.

Abstract licence: CC BY-NC

IntroductionCurrent Belgian guidelines state that chronic proton pump inhibitor (PPI) therapy is indicated for oesophagitis grade C and D, Barrett's oesophagus, Zollinger-Ellison syndrome, or to prevent bleeding ulcers with chronic non-steroidal anti-inflammatory drugs (NSAID) intake in patients at risk. Guidelines justify empiric short-term PPI therapy in other cases to control symptoms. Yet, there is insufficient PPI down-titration and/or cessation. As such, concerns have risen related to the impact of PPIs on the healthcare budget and increasing number of risks and side effects. This study aims to provide evidence to determine which strategy provides the most effective approach for stopping chronic intake of PPIs in patients in whom there is no firm medical indication for their continued use.Methods and analysisThis is a multicentre, pragmatic, randomised clinical trial. General practitioners will randomise 609 to one of three PPI deprescription strategies. Patients on a high-dose PPI are allowed to participate after down-titrating their dose to a maintenance dose for 1 month before being randomised. Patients unable to decrease the high-dose PPI are not to be randomised. Following randomisation, patients will be requested to adapt their PPI intake for 1 month to the allocated deprescription scheme: (a) on-demand PPI intake, (b) replace PPI to alginate intake and (c) intermittent PPI intake with a fixed scheme. After successfully following the deprescription strategy, patients are requested to completely stop their use of PPI. Patients are followed up for 1 year. The primary endpoint of the study is the percentage of patients achieving a successful therapeutic outcome, defined as limited PPI intake and willingness to continue the therapy, at the end of the follow-up period. Data will be collected using a study-specific online platform and analysed using the intention-to-treat approach.Ethics and disseminationThis trial was approved through the platform for Clinical Trials in the European Union by a Belgian ethics committee (CTIS reference: 2022-502375-37-00). Study results will be disseminated via open-access, peer-reviewed publications and conference presentations. Trial registration number NCT05629143.Trial registration numberNCT05629143, clinicaltrial.gov.

Abstract licence: CC BY-NC