Development and evaluation of an antimicrobial urinary catheter

Over the past few years the healthcare setting has seen a vast increase in the use of medical devices and whilst this may have improved clinical outcomes for patients their increase in use has given rise to an increase in medical - device associated infections. It has been reported that urinary tract infections (UTIs) account for up to 40% of all healthcare associated infections and about 80% of those are associated with catheter use [1]. Urinary catheters are hollow, flexible, tubular devices designed to drain urine when inserted into a patient‟s bladder. They are widely used both on patients requiring short - term urinary catheterisation e.g. during and after some types of surgical procedures or long - term urinary catheterisation e.g. due to urinary incontinence. For patients undergoing long - term indwelling urinary catheterisation (LTC) it is almost inevitable that their catheter will become colonised with bacteria and a biofilm (an accumulation of microorganisms and their extracellular products that form a functional, structured community on a surface) [2] develop which can result in a symptomatic or asymptomatic catheter associated urinary tract infection (CAUTI). Infections associated with biofilms are difficult to treat due to the bacteria within the biofilm being insusceptible to antibiotic treatment. Often to resolve the infection, removal and replacement of the catheter is required and antibiotic treatment if necessary. Certain patients may require their catheter to be changed frequently, often causing considerable distress and morbidity and giving rise to increased medical costs. Biomaterials used to produce long - term urinary catheters that are able to completely resist bacterial colonisation for significant periods, remain elusive. The development of antimicrobial urinary catheters has, however, shown some success in clinical trials but only in the short-term. This project proposes to modify a silicone urinary catheter used for LTC by impregnating it with a suitable combination and concentration of antimicrobial agents. The aim of the study is to develop an antimicrobial catheter that will provide protection from bacterial colonisation and subsequent biofilm development by the principle organisms involved in CAUTIs over a prolonged period (12 weeks). Silicone material was processed using an impregnation method. A variety of agents were assessed using drug screening tests to establish their potential duration of antimicrobial activity and ability to prevent bacterial colonisation. The combination of agents showing the most potential were selected and impregnated into the catheter material. They were: rifampicin, sparfloxacin and triclosan. Further testing involved the development of an in - vitro model designed to test the ability of the antimicrobial catheter to resist colonisation following repeated bacterial challenges. The emergence of bacterial resistance was also monitored during this time. In addition, the total antimicrobial content, drug release profiles and uniformity of drug distribution were elucidated using high performance liquid chromatography (HPLC) and time of flight secondary ion mass spectroscopy (ToF-SIMS) respectively. The effect impregnating antimicrobial agents into the catheter had on its surface properties and the impact on mechanical performance of the catheter shaft and balloons were also examined. Drug screening tests revealed a combination of rifampicin, sparfloxacin and triclosan had the potential to deliver a long duration of protective activity against principal uropathogens. In - vitro model results demonstrated the antimicrobial catheter was able to prevent colonisation by Escherichia coli and Meticillin Resistant Staphylococcus aureus for >12 weeks, Klebsiella pneumoniae and Proteus mirabilis for 8 weeks but only 8 days against Enterococcus faecalis. K.pneumoniae and P.mirabilis colonised catheters did, however, show an increase in the sparfloxacin and triclosan minimum inhibitory concentrations (MICs), highlighting that the development of bacterial resistance could be an issue. The catheter was found to contain (w/w) 0.006% rifampicin, 0.16% sparfloxacin and 0.17% triclosan of which 19.8% sparfloxacin and 29.9% triclosan were released by a diffusion process over the first 28 days. Rifampicin release was not detected possibly due to low concentrations. With the drug release trend suggesting a continued steady release of sparfloxacin and triclosan above the MIC and with 80.2% of sparfloxacin and 70.1% of triclosan remaining, this would suggest there should be sufficient drug to provide protection from bacterial colonisation over a 12 week duration. However, why the MICs increased as catheters became colonised with K.pneumoniae and P.mirabilis could be due to a number of factors. ToF-SIMS revealed the drugs which could be traced (sparfloxacin and triclosan) were mostly uniformly distributed on the catheter surface, with some drug localization being seen which may have added to the initial burst effect and could be important in the prevention of bacterial colonisation during catheter insertion. Surface analysis techniques also showed the incorporation of antimicrobial agents lead to an increase in the surface hydrophilicity but following exposure to an aqueous environment no difference was seen compared to control catheters. As drugs eluted from the catheter the surface topography marginally deteriorated but the impact of this in terms of bacterial colonisation is not thought to be of a clinical significance. No adverse affect to the mechanical performance of the antimicrobial catheter shaft or balloon compared to the conventional silicone Foley urinary catheter was shown, indicating that it would be as mechanically stable as the catheter in clinical use and therefore suitable if applied to clinical practice. Further work on the drug release concentrations and ratios are needed to help overcome the potential of bacterial resistance. The catheter could have a greater effect on reducing bacterial colonisation and potential for resistance development if drug concentrations were adjusted to release at higher concentrations and equal ratios and more data could be gathered if drug release studies were taken to the end point of 12 weeks rather than 28 days. In - vitro model challenges using urine as the perfusion medium and a larger array of microorganisms is required and investigations are also necessary to assess the antimicrobial catheters ability to prevent encrustation, a further complication of LTC. This preliminary study has shown with further work there is potential that the antimicrobial catheter could have a substantial effect on reducing/delaying colonisation by several of the main organisms involved in CAUTIs over a prolonged course. This in turn would help reduce CAUTI rates, reduce the frequency at which catheters need to be replaced and improve the quality of life for patients on LTC

Contaminant transport in natural sediments: influence of soil organic matter and Fe/Al-oxyhydroxides on heavy metals (Cu, Zn) and nanoparticles (titanium dioxide)

Contaminant transport in subsurface environments may be significantly influenced by contents of aquifer sediments, such as soil organic matter (SOM) and Fe/Al-oxyhydroxides, though their effects are not fully known. This thesis systematically explored the influences of SOM and Fe/Al-oxyhydroxides on two common groundwater contaminants, engineered nanoparticles (titanium dioxide nTiO2) and heavy metals (Cu and Zn), in two projects using the same natural sediment. Project 1 found dissolved SOM enhanced nTiO₂ transport by adsorbing onto nTiO₂ surface and stabilizing it in suspension, whereas solid SOM and Fe/Al-oxyhydroxides reduced transport by attracting nTiO₂ when surface charges were opposite. In project 2, Cu adsorption was strongly dependent on SOM and Fe/Al-oxyhydroxide content, with lesser effects for Zn. Depleted SOM decreased adsorption when pH was 6.5. Both projects contributed to knowledge of the roles of SOM and Fe/Al-oxyhydroxides in governing contaminant transport in natural sediments

Value-adding to health professional student placement experiences: Enhancing work readiness and employability through a rural community engagement program

Enriching health professional students’ placement experiences through targeted community-engagement has the potential to help develop their preparedness to provide healthcare to the broader community. The program, developed in 2011, consisted of short, extracurricular community-engaged learning experiences integrated with the students’ professional placements. The aim of this study was to investigate whether the program was adding to the students’ rural health placement experiences based on perceptions of both the students themselves and UONDRH staff. A mixed methods approach used a student survey (n = 96), which included both closed and open-ended questions, and semi-structured interviews with staff members involved in delivery of the community engagement program (n = 15). Data were explored together for intersections and commonalities. The overarching key concept was ‘Enhancing Work Readiness and Employability’. Both student and staff perceived that students’ participation in community engagement improved their employment prospects. Three themes that emerged from the data, which underpinned and supported the key concept. They were: ‘Expanding professional practice capabilities’; ‘Building confidence and showing motivation’ and ‘Better understanding the nature of rural practice’,   The results of this study provide support to the notion that there was value for students in this form of short-term, community engagement activities, many of which could be readily integrated into existing health professional education programs with considerable benefits. . It would also lend itself to other non-health professional programs, such as law, journalism or business studies, as a means of broadening the students’ perspectives beyond the limits of their own professional horizons

Osteogenic and bactericidal surfaces from hydrothermal titania nanowires on titanium substrates

Nanotopographical cues on Ti have been shown to elicit different cell responses such as cell differentiation and selective growth. Bone remodelling is a constant process requiring specific cues for optimal bone growth and implant fixation. Moreover, biofilm formation and the resulting infection on surgical implants is a major issue. Our aim is to identify nanopatterns on Ti surfaces that would be optimal for both bone remodelling and for reducing risk of bacterial infection. Primary human osteoblast/osteoclast co-cultures were seeded onto Ti substrates with TiO2 nanowires grown under alkaline conditions at 240 °C for different times (2, 2.5 or 3 h). Cell growth and behaviour was assessed by scanning electron microscopy (SEM), immunofluorescence microscopy, histochemistry and quantitative RT-PCR methods. Bacterial colonisation of the nanowire surfaces was also assessed by confocal microscopy and SEM. From the three surfaces tested the 2 h nanowire surface supported osteoblast and to a lesser extent osteoclast growth and differentiation. At the same time bacterial viability was reduced. Hence the 2 h surface provided optimal bone remodeling in vitro conditions while reducing infection risk, making it a favourable candidate for future implant surfaces

Information needs of ethnically diverse, vaccine-hesitant parents during decision-making about the HPV vaccine for their adolescent child:a qualitative study

BackgroundThe English schools-based human papillomavirus (HPV) vaccination programme has the potential to eliminate HPV-related cancers if high uptake is achieved. However, unmet information needs among some parents may contribute to persisting lower uptake among minority ethnic groups. Through this study we aimed to understand the information needs of vaccine-hesitant, ethnically diverse parents during decision-making about the HPV vaccine for their adolescent child, to inform the future development of tailored communication materials.MethodsRecruitment was facilitated thorough healthcare and community organisations within London and the South West of England. Semi-structured interviews took place between April and August 2023. Thematic analysis was undertaken, assisted by NVivo software.ResultsOf the 29 parents interviewed, the majority were mothers (79%), belonged to a minority ethnic group (88%), and had an adolescent child unvaccinated against HPV (72%). Five of the interviews were undertaken in the participants’ primary language with translation support. Most parents interviewed had limited knowledge about the HPV vaccine and appeared conflicted as to whether vaccines could offer benefits to health. Misunderstanding around the potential of developing serious side-effects (e.g. fertility issues, developing cancer) were factors that could negatively impact decision-making by parents. Stigma associated with the sexual transmissibility of HPV did not always negatively impact decision-making. However, some parents chose not to vaccinate on the basis of perceptions of low risk and a preference to provide education about sexual behaviours to their adolescent child.ConclusionsTailoring communication materials to address misunderstandings could support informed decision-making by vaccine hesitant parents for their adolescent children to be vaccinated against HPV. Future communication materials about the HPV vaccine should highlight the benefits of protection against cancer to increase parents’ motivation for protect their adolescent child; provide accurate convincing information in relation to the excellent safety profile; and emphasise the importance of providing HPV vaccine at the recommended age, all alongside communicating the universality and commonality of HPV infection

A large-scale experiment finds no evidence that a seismic survey impacts a demersal fish fauna

Seismic surveys are used to locate oil and gas reserves below the seabed and can be a major source of noise in marine environments. Their effects on commercial fisheries are a subject of debate, with experimental studies often producing results that are difficult to interpret. We overcame these issues in a large-scale experiment that quantified the impacts of exposure to a commercial seismic source on an assemblage of tropical demersal fishes targeted by commercial fisheries on the North West Shelf of Western Australia. We show that there were no short-term (days) or long-term (months) effects of exposure on the composition, abundance, size structure, behavior, or movement of this fauna. These multiple lines of evidence suggest that seismic surveys have little impact on demersal fishes in this environment

Development of a multicomponent intervention to increase parental vaccine confidence and young people's access to the universal HPV vaccination programme in England: protocol for a co-design study.

INTRODUCTION: Persistent infection with HPV can result in cancers affecting men and, especially, women. Lower uptake exists by area and different population groups. Increasing parental confidence about, and adolescent access to, the universal HPV vaccination programme may help reduce inequalities in uptake. However, the evidence-base for interventions to address uptake for schools-based HPV vaccination programmes is currently lacking. This study protocol outlines how a multicomponent intervention to address this evidence gap will be codesigned with parents. METHODS AND ANALYSIS: The proposed research will be undertaken in localities covered by two immunisation teams in London and the south-west of England. The 'person-based approach' to intervention development will be followed. In the first phase, an exploratory qualitative study will be undertaken with key stakeholders (n=8) and parents (n=40) who did not provide consent for their adolescent child to be vaccinated. During the interviews, parents' views on ways to improve parental confidence about, and adolescents' access to, HPV vaccination will be sought. The findings will be used to inform the co-design of a preliminary plan for a targeted, multicomponent intervention. In the second phase, at least two parent working groups (n=8) will be convened and will work with creative designers to co-design communication materials aimed at increasing parents' confidence in vaccination. At least two workshops with each parent group will be organised to obtain feedback on the intervention plan and communication materials to ensure they are fit for purpose. These findings will inform a protocol for a future study to test the effectiveness of the intervention at increasing HPV vaccination uptake. ETHICS AND DISSEMINATION: The National Health Services Research Ethics Service and London School of Hygiene & Tropical Medicine Observational / Interventions Research Ethics Committee provided approvals for the study (reference 22/SW/0003 & 26902, respectively). We will work with parent advisory groups to inform our dissemination strategy and co-present our findings (eg, at community events or through social media). We will disseminate our findings with academics and healthcare professionals through webinars and academic conferences, as well as peer-reviewed publications

Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo

© 2020 The Author(s) Implantation of medical devices can result in inflammation. A large library of polymers is screened, and a selection found to promote macrophage differentiation towards pro- or anti-inflammatory phenotypes. The bioinstructive properties of these materials are validated within a rodent model. By identifying novel materials with immune-instructive properties, the relationship between material-immune cell interactions could be investigated, and this offers exciting possibilities to design novel bioinstructive materials that can be used for numerous clinical applications including medical implants