Effect of Different Media on the Bactericidal Activity of Colistin and on the Synergistic Combination With Azidothymidine Against mcr-1-Positive Colistin-Resistant Escherichia coli

Antimicrobial susceptibility testing (AST) performed according to defined guidelines is important to identify resistance and to predict the clinical success or failure of specific antibiotic therapy. However, these guidelines do not cover all physiological conditions that can have a tremendous impact on in vivo resistance. In this study, we tested the susceptibility of thirteen mcr-1-positive Escherichia coli strains against colistin, one of the last resort antibiotics for treating multi-drug resistant pathogens, in media recommended for ASTs as well as – physiologically more relevant – in human serum and artificial urine (AU). Minimal inhibitory concentration (MIC) values in heat-inactivated human serum were similar to those in cation-adjusted Mueller-Hinton broth (CAMHB), but reduced in native serum for almost all strains that could grow in this media. In AU MIC values for mcr-1 positive E. coli were increased significantly up to 16-fold compared to that in CAMBH, which did not apply to the colistin-susceptible E. coli strains tested. Although different growth media could affect the MIC of colistin alone, their impact on the synergistic effect of the combination with the antiviral drug azidothymidine was minimal. The higher divalent cation concentration combined with acidic pH values is most likely responsible for the increased MIC values of the mcr-1 harboring E. coli strains tested against colistin in AU compared to that in CAMHB. Antimicrobial susceptibility screening procedures for colistin using CAMHB only could lead to an underestimation of resistance under different physiological conditions. Therefore, not only pharmacokinetic but also pharmacodynamic studies in urine are as important as in serum or plasma

Serum bactericidal activity of colistin and azidothymidine combinations against mcr-1 positive colistin-resistant Escherichia coli.

To examine the serum bactericidal activity of colistin-sulphate (CS) and azidothymidine (AZT) combinations, time-kill curves were performed in native and heat-inactivated human serum with five colistin-resistant and four colistin-susceptible Gram-negative strains. The serum samples were spiked according to the median and minimum plasma peak concentrations measured in a phase 1 clinical study, in which seven healthy subjects received 3-times (q12) 1h-IV-infusions of 4, 2 and 2 million international units (MIU) colistin-methanesulfonate (CMS) co-administered with 200, 100 and 100 mg AZT, respectively. This trial was performed to assess the pharmacokinetics and safety of CMS/AZT-combination therapy. Minimal bactericidal concentrations of CS in native, but not heat-inactivated serum, were strongly reduced compared to Mueller-Hinton-Broth for all tested Enterobacteriaceae, except one colistin-resistant (serum-resistant) strain. For colistin-susceptible strains, the minimum CS concentration after 2 MIU CMS dosage was already bactericidal in native and heat-inactivated serum. Median, but not minimum, CS concentrations after 2 MIU CMS dosage were sufficient to kill the serum-resistant, colistin-resistant E.coli strain in native serum. In heat-inactivated serum, even the median CS concentration after 2 MIU CMS dosage was not bactericidal for all colistin-resistant strains. In general, combinations with AZT accelerated killing of colistin-resistant E.coli or showed bactericidal activity even if the substances alone were not bactericidal. Thus, the combination with AZT potentiates the bactericidal effect of colistin against colistin-resistant E.coli strains. Although the dosage of 2 MIU CMS plus AZT may be sufficient to treat infections with colistin-susceptible strains, for infections caused by colistin-resistant E.coli the dosing should be further optimized

User needs elicitation via analytic hierarchy process (AHP). A case study on a Computed Tomography (CT) scanner

Background: The rigorous elicitation of user needs is a crucial step for both medical device design and purchasing. However, user needs elicitation is often based on qualitative methods whose findings can be difficult to integrate into medical decision-making. This paper describes the application of AHP to elicit user needs for a new CT scanner for use in a public hospital. Methods: AHP was used to design a hierarchy of 12 needs for a new CT scanner, grouped into 4 homogenous categories, and to prepare a paper questionnaire to investigate the relative priorities of these. The questionnaire was completed by 5 senior clinicians working in a variety of clinical specialisations and departments in the same Italian public hospital. Results: Although safety and performance were considered the most important issues, user needs changed according to clinical scenario. For elective surgery, the five most important needs were: spatial resolution, processing software, radiation dose, patient monitoring, and contrast medium. For emergency, the top five most important needs were: patient monitoring, radiation dose, contrast medium control, speed run, spatial resolution. Conclusions: AHP effectively supported user need elicitation, helping to develop an analytic and intelligible framework of decision-making. User needs varied according to working scenario (elective versus emergency medicine) more than clinical specialization. This method should be considered by practitioners involved in decisions about new medical technology, whether that be during device design or before deciding whether to allocate budgets for new medical devices according to clinical functions or according to hospital department

Multilayer Modelling of Lubricated Contacts: A New Approach Based on a Potential Field Description

A first integral approach, derived in an analogous fashion to Maxwell’s use of potential fields, is employed to investigate the flow characteristics, with a view to minimising friction, of shear-driven fluid motion between rigid surfaces in parallel alignment as a model for a lubricated joint, whether naturally occurring or engineered replacement. For a viscous bilayer arrangement comprised of immiscible liquids, it is shown how the flow and the shear stress along the separating interface is influenced by the mean thickness of the layers and the ratio of their respective viscosities. Considered in addition, is how the method can be extended for application to the more challenging problem of when one, or both, of the layers is a viscoelastic material

Infrastructural requirements for local implementation of safety policies: the discordance between top-down and bottom-up systems of action

<p>Abstract</p> <p>Background</p> <p>Safety promotion is planned and practised not only by public health organizations, but also by other welfare state agencies, private companies and non-governmental organizations. The term 'infrastructure' originally denoted the underlying resources needed for warfare, e.g. roads, industries, and an industrial workforce. Today, 'infrastructure' refers to the physical elements, organizations and people needed to run projects in different societal arenas.</p> <p>The aim of this study was to examine associations between infrastructure and local implementation of safety policies in injury prevention and safety promotion programs.</p> <p>Methods</p> <p>Qualitative data on municipalities in Sweden designated as Safe Communities were collected from focus group interviews with municipal politicians and administrators, as well as from policy documents, and materials published on the Internet. Actor network theory was used to identify weaknesses in the present infrastructure and determine strategies that can be used to resolve these.</p> <p>Results</p> <p>The weakness identification analysis revealed that the factual infrastructure available for effectuating national strategies varied between safety areas and approaches, basically reflecting differences between bureaucratic and network-based organizational models. At the local level, a contradiction between safety promotion and the existence of quasi-markets for local public service providers was found to predispose for a poor local infrastructure diminishing the interest in integrated inter-agency activities. The weakness resolution analysis showed that development of an adequate infrastructure for safety promotion would require adjustment of the legal framework regulating injury data exchange, and would also require rational financial models for multi-party investments in local infrastructures.</p> <p>Conclusion</p> <p>We found that the "silo" structure of government organization and assignment of resources was a barrier to collaborative action for safety at a community level. It may therefore be overly optimistic to take for granted that different approaches to injury control, such as injury prevention and safety promotion, can share infrastructure. Similarly, it may be unrealistic to presuppose that safety promotion can reach its potential in terms of injury rate reductions unless the critical infrastructure for this is in place. Such an alignment of the infrastructure to organizational processes requires more than financial investments.</p

How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease

European Respiratory Society International Congress, Barcelona, 2022: Highlights from the Respiratory clinical care and physiology assembly

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of the Assembly 1 – Respiratory clinical care and physiology. Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging

Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: a case-control study

<p>Abstract</p> <p>Background</p> <p>Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) - an important health issue in the aging male population in the Western world - belongs to these conditions has been a matter of research since the 1970 s. Persistent serum antibodies are a proof of present or past infection. The aim of this study was to compare serum antibodies against genitourinary infectious agents between PCa patients and controls with benign prostate hyperplasia (BPH). We hypothesized that elevated serum antibody levels or higher seroprevalence in PCa patients would suggest an association of genitourinary infection in patient history and elevated PCa risk.</p> <p>Methods</p> <p>A total of 434 males who had undergone open prostate surgery in a single institution were included in the study: 329 PCa patients and 105 controls with BPH. The subjects' serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for the presence of antibodies against common genitourinary infectious agents: human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings.</p> <p>Results</p> <p>PCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.08-4.28). Men with BPH were more often seropositive for HPV 18 and Chlamydia trachomatis (OR 0.23; 95% CI 0.09-0.61 and OR 0.45; 95% CI 0.21-0.99, respectively) and had higher mean serum CMV antibody levels than PCa patients (p = 0.0004). Among PCa patients, antibodies against HPV 6 were associated with a higher Gleason score (p = 0.0305).</p> <p>Conclusions</p> <p>Antibody seropositivity against the analyzed pathogens with the exception of Ureaplasma does not seem to be a risk factor for PCa pathogenesis. The presence or higher levels of serum antibodies against the genitourinary pathogens studied were not consistently associated with PCa. Serostatus was not a predictor of disease stage in the studied population.</p

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients

\ua9 2024, European Respiratory Society. All rights reserved.Background Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods A systematic review was performed identifying studies that reported in-hospital mortality, postdischarge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisation

A novel TOPSIS–CBR goal programming approach to sustainable healthcare treatment

Cancer is one of the most common diseases worldwide and its treatment is a complex and time-consuming process. Specifically, prostate cancer as the most common cancer among male population has received the attentions of many researchers. Oncologists and medical physicists usually rely on their past experience and expertise to prescribe the dose plan for cancer treatment. The main objective of dose planning process is to deliver high dose to the cancerous cells and simultaneously minimize the side effects of the treatment. In this article, a novel TOPSIS case based reasoning goal-programming approach has been proposed to optimize the dose plan for prostate cancer treatment. Firstly, a hybrid retrieval process TOPSIS–CBR [technique for order preference by similarity to ideal solution (TOPSIS) and case based reasoning (CBR)] is used to capture the expertise and experience of oncologists. Thereafter, the dose plans of retrieved cases are adjusted using goal-programming mathematical model. This approach will not only help oncologists to make a better trade-off between different conflicting decision making criteria but will also deliver a high dose to the cancerous cells with minimal and necessary effect on surrounding organs at risk. The efficacy of proposed method is tested on a real data set collected from Nottingham City Hospital using leave-one-out strategy. In most of the cases treatment plans generated by the proposed method is coherent with the dose plan prescribed by an experienced oncologist or even better. Developed decision support system can assist both new and experienced oncologists in the treatment planning process