Individualized prescribing portraits to reduce inappropriate initiation of opioid analgesics to opioid naïve patients in primary care: Protocol for a randomized controlled trial.

Background Opioid analgesics are frequently initiated for chronic and acute pain despite weak evidence of benefit, although prescribing rates of some analgesics decreased in the context of the epidemic. In some populations, up to a quarter of opioid naïve persons prescribed opioids for non-cancer pain develop prescription opioid use disorder (OUD). Audit and feedback interventions rely on constructive use of routinely collected data to align professional behaviours and clinical practice with best evidence. These interventions have been shown to help reduce inappropriate initiation. However, effectiveness and acceptability of individualized "portraits" of physicians' prescribing patterns, to reduce inappropriate initiation of opioid analgesics to opioid naïve persons, have not been evaluated. Methods REDONNA is a mixed-methods randomized study testing the effectiveness of individualized prescribing Portraits to reduce inappropriate initiation of opioid analgesics. This intervention to improve safety of opioid prescribing in primary care in British Columbia (BC), Canada involves mailing individual prescribing portraits to an 'early group' of 2604 family physicians, followed in 6 months by a mailing to 2553 family physicians in the 'delayed group'. Primary outcome is number of new opioid prescriptions initiated in opioid naïve people, measured using administrative data from a centralized medication monitoring database covering all prescription opioids dispensed from BC community pharmacies. Secondary endpoints will compare prescribing impact between the two groups. A qualitative sub-study will examine feasibility among a purposive sample of physicians and patients. Discussion This trial provides important evidence on the intervention's potential to steer policy and practice on inappropriate opioid analgesics initiation. Trial registration: The study was registered prospectively on 30 March 2020 at the ISRCTN Register (https://www.isrctn.com/ISRCTN34246811).

Development of antibacterial and antifungal silver-coated polyurethane foams as air filtration units for the prevention of respiratory diseases.

AIM: The development of silver-coated polyurethane filters as filtration units for the prevention of the respiratory diseases. METHODS AND RESULTS: An innovative silver deposition technology based on the photo-reduction in a silver salt was adopted. The efficacy of the technology in providing a homogeneous distribution of the silver particles was verified by scanning electron microscopy and energy dispersive X-ray spectroscopy. The materials were tested through microbiological procedures used in industry to verify the efficacy of the silver-coated filters on the viability and growth of selected micro-organisms. Direct inoculation test, filtration experiment and shaking tests were performed on microbial human pathogens associated with air filtration units and respiratory disease, namely Legionella pneumophila, Pseudomonas aeruginosa, Aspergillus niger and Aspergillus flavus, by adopting Escherichia coli and Staphylococcus aureus as control organisms. CONCLUSIONS: The results provided evidence of the effectiveness of the silver coating in reducing the bioaerosolization of viable human pathogens into environments using recirculated air. SIGNIFICANCE AND IMPACT OF THE STUDY: Micro-organisms can affect the air quality in indoor environments and can be responsible for infectious, allergic or toxic disturbances on human airways. The development of an adequate bioaerosol control might ameliorate a positive health effect in humans.

Silver-doped self-assembling di-phenylalanine hydrogels as wound dressing biomaterials.

Chronic and acute wounds can be quickly contaminated and infected by microorganisms such as bacteria, multi-resistant organisms or fungi. The introduction of silver as anti-microbial agent into wound management has widely been demonstrated to be effective and contribute to wound healing. As a consequence, many approaches and different materials have been employed to synthesize antibacterial silver-hydrogels. In this work the introduction of silver particles into the fibrillar structure of self-assembling aromatic di-phenylalanine derivatives modified with aromatic groups such as 9-fluorenylmethoxycarbonyl is proposed to produce antibacterial wound dressings. Hydrogels doped with increasing amounts of silver were tested and adopted to modify flax textiles. The influence of silver on the structure of hydrogels was studied using light and confocal microscopy, while SEM-EDX allowed the characterization of the hydrogel coating on the surface of the textile substrates as well as the identification and distribution of silver nanoparticles. The antibacterial potential of the treated flax was demonstrated through microbiological tests on Staphylococcus aureus. The combination of the physico-chemical and anti-bacterial properties, together with the ease of preparation of these biomaterials, fulfils the requirement of clinically-effective wound dressings.

Resistance of Legionella pneumophila serotype 1 biofilms to chlorine-based disinfection.

The presence of Legionella spp. in potable water systems is a major concern to municipal water providers and consumers alike. Despite the inclusion of chlorine in potable supplies and frequent chlorination cycles, the bacterium is a recalcitrant human pathogen capable of causing incidents of Legionnaires' disease, Pontiac fever and community-acquired pneumonia in humans. Using two materials routinely employed for the delivery of potable water as a substratum, copper and stainless steel, the development of Legionella pneumophila biofilms and their response to chlorination was monitored over a three-day and a three-month period, respectively. Preliminary in vitro studies using broth and sterile tap water as culture media indicated that the bacterium was capable of surviving in low numbers for 28 days in the presence of chlorine. Subsequently, biofilms were grown for three days, one month and two months, respectively, on stainless steel and copper sections, which are widely used for the conveyance of potable water. Immediately after exposure to 50mg/L chlorine for 1h, the biofilms yielded no recoverable colonies, but colonies did reappear in low numbers over the following days. Despite chlorination at 50mg/L for 1h, both one- and two-month-old L. pneumophila biofilms were able to survive this treatment and to continue to grow, ultimately exceeding 1x10(6)cfu per disc. This research provides an insight into the resistance afforded to L. pneumophila against high levels of chlorine by the formation of biofilms and has implications for the delivery of potable water.

The rapid and specific real-time detection of Legionella pneumophila in water samples using Optical Waveguide Lightmode Spectroscopy.

The detection of Legionella pneumophila in water samples using standard microbiological culture techniques is both prolonged and problematic. The bacterium is slow-growing and nutritionally fastidious, such that other indigenous species can out-compete the Legionella even when using antibiotic supplemented media. Optical Waveguide Lightmode Spectroscopy (OWLS) is a real-time analytical system whereby a change to a higher coupling angle where the refractive index of a bacterial cell is higher than that of the covering medium. In this study an aqueous suspension of L. pneumophila was passed across the surface of waveguides functionalised with a specific anti-Legionella antibody. The binding between the bacterial cells and the antibody specific for that cell resulted in an increase in the refraction indices of the transverse electric and transverse magnetic photoelectric currents. We report the optimisation of a rapid and sensitive (1.3 x 10(4) CFU mL-1) detection method for L. pneumophila contamination in a water sample in less than 25 min. This is a significant reduction in the time taken to determine the presence of the bacterium which with conventional techniques normally takes up to fourteen days. In addition, the specificity of the technique to L. pneumophila was demonstrated. The OWLS results were validated by conventional microbiology screening and atomic force microscopy of the surface of the waveguide, showing its species specificity and potential applications in environmental and clinical analysis.

Long-term persistence of a single Legionella pneumophila strain possessing the mip gene in a municipal shower despite repeated cycles of chlorination.

The ability of Legionella pneumophila to colonise domestic water systems is a primary cause of outbreaks of Legionnaire's disease in humans. World Health Organization guidelines recommend that drinking water is chlorinated to between 0.2 and 1mg/L [Chlorine in drinking-water. Guidelines for drinking-water quality, 2nd edn. Geneva: World Health Organization; 1996], but L. pneumophila is repeatedly isolated from chlorinated water systems, indicating that this treatment is not effective at preventing colonisation. Current UK guidelines recommend a one-off treatment of 20-50mg/L of free chlorine to remove the bacteria. In this study we report on the persistence of L. pneumophila serogroup 1 in a domestic shower system despite repeated cycles of chlorination at 50mg/L for 1h exposure time, over the course of two and a half years. Persisting isolates were subjected to in-vitro phenotypic analyses and polymerase chain reaction analysis for the toxin-encoding mip gene. Random amplified polymorphic DNA typing was also performed to determine whether the isolates recovered on different occasions were the same strain. We found that seven isolates of L. pneumophila recovered over a two-and-a-half year period are the same genetically defined strain, indicating that the bacteria can persist despite repeated cycles of chlorination after each successive isolation.

Virulence traits associated with verocytotoxigenic Escherichia coli O157 recovered from freshwater biofilms.

AIM: To investigate whether epilithic biofilms in freshwater streams in a mixed UK agricultural river catchment harbour Escherichia coli O157, and if so, whether they demonstrate an association with those excreted by grazing farm animals. METHODS AND RESULTS: Flint shingle, native to the study site, was used as a surface for biofilm development within cages of metal lath set into a stream bed at four locations on a chalkland farm. Shingle was collected from all sites once a month, as were pooled faecal samples from five farm animal populations. Subpopulations of E. coli, including E. coli O157 that demonstrated significant phenotypic and genotypic similarity with animal faecal isolates (t-test, P = 0.05) were isolated. Of 1002 E. coli isolates from biofilms and animal faeces, 48 were confirmed as the O157 strain by latex agglutination. The presence of five virulence traits associated with incidence of human disease was tested using PCR. Stx(2) was the most frequently isolated single gene (30 isolates), while stx(1) was the least frequently recovered (four isolates). CONCLUSION: Escherichia coli O157, expressing up to four virulence factors associated with human disease, reside within freshwater biofilms in this agricultural environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Aquatic biofilms may potentially act as a reservoir for these pathogens, and the implications of the findings for the protection of drinking water resources should be further investigated.

Effects of differential overexpression of Bcl-2 on apoptosis, proliferation, and telomerase activity in Jurkat T cells.

The effects of Bcl-2 overexpression on several of its multifunctional characteristics, which include anti-apoptotic properties, impeding of cell proliferation, and telomerase activity, were examined in four Jurkat T cell clones overexpressing different levels of Bcl-2. When treated with anti-Fas or staurosporine, only three of the four clones showed resistance to apoptosis that correlated with the level of Bcl-2 expression. Surprisingly, the clone having no anti-apoptotic characteristic expressed the highest level of Bcl-2. When all the clones were treated with anti-Fas the processing of caspase-2, -3, and -7 but not -8 was inhibited in the resistant clones to a similar extent by the differential overexpression of Bcl-2. However, with staurosporine treatment the processing of all the caspases examined was inhibited to a similar degree by the different levels of Bcl-2 expression in the resistant clones. These results suggest that Bcl-2 blocked Fas-mediated cell death by acting downstream of caspase-8, which is in contrast to staurosporine-induced apoptosis where Bcl-2 is acting upstream of caspase-8. When the anti-proliferative effect of Bcl-2 was examined, a direct correlation between a decrease in cell proliferation and the level of Bcl-2 overexpressed in the clones was observed. The clone overexpressing the greatest amount of Bcl-2 protein, which had no resistance to apoptosis, had the slowest proliferative rate. This suggests that the anti-apoptotic effect of Bcl-2 can be separated from its anti-proliferative effect. The possible effect of overexpression of Bcl-2 on telomerase activity, which is known to control the proliferative capacity of normal cells and cellular senescence, was also determined. Our results suggest that Bcl-2 had no effect on telomerase activity or telomere length in the clones. In summary, our results further suggest that some properties of Bcl-2, such as anti-apoptotic and inhibition of cell proliferation, are individual features of a multifaceted protein.

Simple computational model of image correlation by four-wave mixing in photorefractive media.

A simple systems-oriented model of image correlation by nondegenerate four-wave mixing in photorefractive media is discussed, and its computational implementation is described. The model is based on a linear-incomplex modulation index formulation and is capable of describing the correlation product in a wide range of experimental conditions. Bragg matching effects on the test and reference images are explicitly included. The comparison of calculated results with experimental results is excellent, and a discussion of higher-order theories of the photorefractive effect is given. The model is currently being used to optimize the performance of experimental correlators.