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1.
Front Public Health ; 11: 1152054, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744522

RESUMO

Objectives: The COVID-19 pandemic has a huge impact on the healthcare system and affects the normal delivery of routine healthcare services to hospitalized patients. This study aimed to examine the differences in patient experience of hospital service before and during COVID-19 among the discharged adult population. Methods: A territory-wide patient experience survey was conducted before and during COVID-19 (between October 2019 and April 2020) among patients discharged from the main acute and rehabilitation public hospitals in Hong Kong. A hierarchical ordinal logistic model was employed to examine the difference in multiple dimensions of patient experience, with adjustments of covariates. Results: In total, 9,800 participants were recruited. During the pandemic, there was a marginally significant increase in overall care rating (AOR: 1.12, 95% CI: 0.99-1.27), and an improvement in the timeliness of admission. However, significant reductions in patients' confidence in nurses were observed. Communication of information regarding medication side effects reduced significantly (AOR: 0.72, 95% CI: 0.64-0.82). Conclusion: The patients hospitalized during the pandemic reported worse responsiveness in communication in their patient journey than those admitted before the pandemic. These findings will help develop appropriate strategies to address patients' concerns in the new normal.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , Pandemias , Comunicação , Hong Kong/epidemiologia , Hospitais
2.
Nat Commun ; 14(1): 5151, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620344

RESUMO

Peptidoglycan (PG) is an essential structural component of the bacterial cell wall that is synthetized during cell division and elongation. PG forms an extracellular polymer crucial for cellular viability, the synthesis of which is the target of many antibiotics. PG assembly requires a glycosyltransferase (GT) to generate a glycan polymer using a Lipid II substrate, which is then crosslinked to the existing PG via a transpeptidase (TP) reaction. A Shape, Elongation, Division and Sporulation (SEDS) GT enzyme and a Class B Penicillin Binding Protein (PBP) form the core of the multi-protein complex required for PG assembly. Here we used single particle cryo-electron microscopy to determine the structure of a cell elongation-specific E. coli RodA-PBP2 complex. We combine this information with biochemical, genetic, spectroscopic, and computational analyses to identify the Lipid II binding sites and propose a mechanism for Lipid II polymerization. Our data suggest a hypothesis for the movement of the glycan strand from the Lipid II polymerization site of RodA towards the TP site of PBP2, functionally linking these two central enzymatic activities required for cell wall peptidoglycan biosynthesis.


Assuntos
Escherichia coli , Peptidil Transferases , Microscopia Crioeletrônica , Escherichia coli/genética , Peptidoglicano , Biologia Molecular , Antibacterianos , Glicosiltransferases
3.
Access Microbiol ; 5(3)2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091736

RESUMO

International development and aid are often conducted through the allocation of funding determined by decisions of non-locals, especially in the west for those in the global south. In addition, such funding is often disassociated from local expertise, therefore providing little long-term developmental impact and generating distrust. This is particularly true for conservation, as well as environmental and educational programmes. We hypothesize that by granting local people the educational tools and the necessary funding to develop their own projects through the use of an applicant-driven peer-review approach, it is possible to relocalize the decision-making process to the programme participants, with the potential to generate and select more relevant projects with developmental outcomes of higher quality. Here we created an online curriculum for antimicrobial resistance (AMR) education that was followed by 89 participants across Ghana, Tanzania, Nigeria and Uganda. We then created an open research programme that facilitated the creation of eight de novo projects on AMR. Finally, we organized an applicant-driven grant round to allocate funding to the 'Neonatal Sepsis in Nigeria' project to conduct a pilot study and awareness campaign. This work opens perspectives for the design of frugal educational programmes and the funding of context-specific, community-driven projects aimed at empowering local stakeholders in the global South.

4.
Opt Express ; 30(24): 43223-43236, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36523025

RESUMO

Photonics-based technologies are key players in a number of emerging applications in the terahertz (THz) field. These solutions exploit the well-known advantages of optical devices, such as ultra-wide tuneability and direct integration with fiber networks. However, THz receivers are mainly implemented by fully electronic solutions, where Schottky barrier diodes (SBD) are the preferred option as detectors and mixers due to their excellent response within the THz range at room temperature, and technological maturity. Here, we demonstrate an SBD-based subharmonic mixer (SHM) at 300 GHz pumped with a photonic local oscillator. The Schottky mixer is a prototype designed and manufactured by ACST GmbH, operating at 270-320 GHz. The local oscillator is generated by photomixing on a high-frequency and high-power uni-travelling-carrier photodiode (UTC-PD), providing enough power to saturate conversion loss. Minimum single-side-band conversion loss of 14.4 dB and a peak dynamic range of 130 dB have been measured. Finally, as a proof of concept we realize an all-photonics-based 5 Gbps wireless bridge, utilizing the optically-pumped SBD mixer. With this work, we prove the feasibility of high-performance hybrid Schottky-photonic THz receivers, incorporating the best of both worlds.

5.
Nature ; 604(7905): 371-376, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35388216

RESUMO

The outer membrane of Gram-negative bacteria has an external leaflet that is largely composed of lipopolysaccharide, which provides a selective permeation barrier, particularly against antimicrobials1. The final and crucial step in the biosynthesis of lipopolysaccharide is the addition of a species-dependent O-antigen to the lipid A core oligosaccharide, which is catalysed by the O-antigen ligase WaaL2. Here we present structures of WaaL from Cupriavidus metallidurans, both in the apo state and in complex with its lipid carrier undecaprenyl pyrophosphate, determined by single-particle cryo-electron microscopy. The structures reveal that WaaL comprises 12 transmembrane helices and a predominantly α-helical periplasmic region, which we show contains many of the conserved residues that are required for catalysis. We observe a conserved fold within the GT-C family of glycosyltransferases and hypothesize that they have a common mechanism for shuttling the undecaprenyl-based carrier to and from the active site. The structures, combined with genetic, biochemical, bioinformatics and molecular dynamics simulation experiments, offer molecular details on how the ligands come in apposition, and allows us to propose a mechanistic model for catalysis. Together, our work provides a structural basis for lipopolysaccharide maturation in a member of the GT-C superfamily of glycosyltransferases.


Assuntos
Ligases , Lipopolissacarídeos , Antígenos O , Proteínas de Bactérias/química , Carbono-Oxigênio Ligases/química , Carbono-Oxigênio Ligases/genética , Microscopia Crioeletrônica , Glicosiltransferases , Bactérias Gram-Negativas , Lipopolissacarídeos/química , Lipopolissacarídeos/metabolismo
6.
Nat Commun ; 13(1): 941, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177595

RESUMO

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. Using a variety of genetic and imaging approaches, we uncover that in the mouse E6.5 epiblast, where apical tension is highest, ASPP2 safeguards tissue integrity. It achieves this by preventing the most apical daughter cells from delaminating apically following division events. In this context, ASPP2 maintains the integrity and organisation of the filamentous actin cytoskeleton at apical junctions. ASPP2 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that it is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling. Finally, our study also suggests that the interaction between ASPP2 and PP1 is essential to the tumour suppressor function of ASPP2, which may be particularly relevant in the context of tissues that are subject to increased mechanical stress.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Epitélio/crescimento & desenvolvimento , Morfogênese , Proteínas Supressoras de Tumor/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Células CACO-2 , Polaridade Celular , Cães , Técnicas de Cultura Embrionária , Embrião de Mamíferos , Epitélio/metabolismo , Feminino , Gastrulação , Camadas Germinativas , Humanos , Células Madin Darby de Rim Canino , Camundongos , Camundongos Transgênicos , Mutação , Linha Primitiva , Receptores de Neuropeptídeo Y/metabolismo , Estresse Mecânico , Junções Íntimas/metabolismo , Proteínas Supressoras de Tumor/genética
7.
J Particip Med ; 14(1): e32125, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060917

RESUMO

BACKGROUND: The rise of major complex public health problems, such as vaccination hesitancy and access to vaccination, requires innovative, open, and transdisciplinary approaches. Yet, institutional silos and lack of participation on the part of nonacademic citizens in the design of solutions hamper efforts to meet these challenges. Against this background, new solutions have been explored, with participatory research, citizen science, hackathons, and challenge-based approaches being applied in the context of public health. OBJECTIVE: Our aim was to develop a program for creating citizen science and open innovation projects that address the contemporary challenges of vaccination in France and around the globe. METHODS: We designed and implemented Co-Immune, a program created to tackle the question of vaccination hesitancy and access to vaccination through an online and offline challenge-based open innovation approach. The program was run on the open science platform Just One Giant Lab. RESULTS: Over a 6-month period, the Co-Immune program gathered 234 participants of diverse backgrounds and 13 partners from the public and private sectors. The program comprised 10 events to facilitate the creation of 20 new projects, as well as the continuation of two existing projects, to address the issues of vaccination hesitancy and access, ranging from app development and data mining to analysis and game design. In an open framework, the projects made their data, code, and solutions publicly available. CONCLUSIONS: Co-Immune highlights how open innovation approaches and online platforms can help to gather and coordinate noninstitutional communities in a rapid, distributed, and global way toward solving public health issues. Such initiatives can lead to the production and transfer of knowledge, creating novel solutions in the public health sector. The example of Co-Immune contributes to paving the way for organizations and individuals to collaboratively tackle future global challenges.

8.
F1000Res ; 11: 1440, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38283124

RESUMO

Resource allocation is essential to selection and implementation of innovative projects in science and technology. Current "winner-take-all" models for grant applications require significant researcher time in writing extensive project proposals, and rely on the availability of a few time-saturated volunteer experts. Such processes usually carry over several months, resulting in high effective costs compared to expected benefits. We devised an agile "community review" system to allocate micro-grants for the fast prototyping of innovative solutions. Here we describe and evaluate the implementation of this community review across 147 projects from the "Just One Giant Lab's OpenCOVID19 initiative" and "Helpful Engineering" open research communities. The community review process uses granular review forms and requires the participation of grant applicants in the review process. Within a year, we organised 7 rounds of review, resulting in 614 reviews from 201 reviewers, and the attribution of 48 micro-grants of up to 4,000 euros. The system is fast, with a median process duration of 10 days, scalable, with a median of 4 reviewers per project independent of the total number of projects, and fair, with project rankings highly preserved after the synthetic removal of reviewers. Regarding potential bias introduced by involving applicants in the process, we find that review scores from both applicants and non-applicants have a similar correlation of r=0.28 with other reviews within a project, matching traditional approaches. Finally, we find that the ability of projects to apply to several rounds allows to foster the further implementation of successful early prototypes, as well as provide a pathway to constructively improve an initially failing proposal in an agile manner. Overall, this study quantitatively highlights the benefits of a frugal, community review system acting as a due diligence for rapid and agile resource allocation in open research and innovation programs, with implications for decentralised communities.


Assuntos
Organização do Financiamento , Redação , Humanos , Pesquisadores
9.
Biol Open ; 10(12)2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34935907

RESUMO

Mouse zygote morphokinetics were measured during interphase, the mitotic period, cytokinesis, and two-cell stage. Sequences of rounder-distorted-rounder shapes were revealed, as were changing patterns of cross section area. A calcium chelator and an actin-disrupting agent inhibited the area changes that occurred between pronuclear envelope breakdown and cytokinesis. During cell division, two vortices developed in each nascent cell and they rotated in opposite directions at each end of the cell, a pattern that sometimes persisted for up to 10 h. Exchange with the environment may have been promoted by these shape and area cycles and persisting circulation in the cytoplasm may have a similar function between a cell's interior and periphery. Some of these movements were sporadically also seen in human zygotes with abnormal numbers of pronuclei and the two-cell stages that developed from these compromised human zygotes.


Assuntos
Núcleo Celular , Zigoto , Animais , Citoplasma , Humanos , Camundongos
10.
Int J Mol Sci ; 22(23)2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34884635

RESUMO

Bacteria must maintain the ability to modify and repair the peptidoglycan layer without jeopardising its essential functions in cell shape, cellular integrity and intermolecular interactions. A range of new experimental techniques is bringing an advanced understanding of how bacteria regulate and achieve peptidoglycan synthesis, particularly in respect of the central role played by complexes of Sporulation, Elongation or Division (SEDs) and class B penicillin-binding proteins required for cell division, growth and shape. In this review we highlight relationships implicated by a bioinformatic approach between the outer membrane, cytoskeletal components, periplasmic control proteins, and cell elongation/division proteins to provide further perspective on the interactions of these cell division, growth and shape complexes. We detail the network of protein interactions that assist in the formation of peptidoglycan and highlight the increasingly dynamic and connected set of protein machinery and macrostructures that assist in creating the cell envelope layers in Gram-negative bacteria.


Assuntos
Membrana Celular/metabolismo , Bactérias Gram-Negativas/metabolismo , Proteínas de Ligação às Penicilinas/metabolismo , Peptidoglicano/metabolismo , Proteínas Periplásmicas/metabolismo , Proteínas de Bactérias/metabolismo , Parede Celular/metabolismo
11.
J Med Internet Res ; 23(10): e31101, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34469327

RESUMO

BACKGROUND: The COVID-19 pandemic has led to changes in health service utilization patterns and a rapid rise in care being delivered remotely. However, there has been little published research examining patients' experiences of accessing remote consultations since COVID-19. Such research is important as remote methods for delivering some care may be maintained in the future. OBJECTIVE: The aim of this study was to use content from Twitter to understand discourse around health and care delivery in the United Kingdom as a result of COVID-19, focusing on Twitter users' views on and attitudes toward care being delivered remotely. METHODS: Tweets posted from the United Kingdom between January 2018 and October 2020 were extracted using the Twitter application programming interface. A total of 1408 tweets across three search terms were extracted into Excel; 161 tweets were removed following deduplication and 610 were identified as irrelevant to the research question. The remaining relevant tweets (N=637) were coded into categories using NVivo software, and assigned a positive, neutral, or negative sentiment. To examine views of remote care over time, the coded data were imported back into Excel so that each tweet was associated with both a theme and sentiment. RESULTS: The volume of tweets on remote care delivery increased markedly following the COVID-19 outbreak. Five main themes were identified in the tweets: access to remote care (n=267), quality of remote care (n=130), anticipation of remote care (n=39), online booking and asynchronous communication (n=85), and publicizing changes to services or care delivery (n=160). Mixed public attitudes and experiences to the changes in service delivery were found. The proportion of positive tweets regarding access to, and quality of, remote care was higher in the immediate period following the COVID-19 outbreak (March-May 2020) when compared to the time before COVID-19 onset and the time when restrictions from the first lockdown eased (June-October 2020). CONCLUSIONS: Using Twitter data to address our research questions proved beneficial for providing rapid access to Twitter users' attitudes to remote care delivery at a time when it would have been difficult to conduct primary research due to COVID-19. This approach allowed us to examine the discourse on remote care over a relatively long period and to explore shifting attitudes of Twitter users at a time of rapid changes in care delivery. The mixed attitudes toward remote care highlight the importance for patients to have a choice over the type of consultation that best suits their needs, and to ensure that the increased use of technology for delivering care does not become a barrier for some. The finding that overall sentiment about remote care was more positive in the early stages of the pandemic but has since declined emphasizes the need for a continued examination of people's preference, particularly if remote appointments are likely to remain central to health care delivery.


Assuntos
COVID-19 , Mídias Sociais , Controle de Doenças Transmissíveis , Atenção à Saúde , Humanos , Pandemias , SARS-CoV-2 , Reino Unido/epidemiologia
12.
BMJ Open ; 10(11): e041709, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243813

RESUMO

OBJECTIVES: The relationship between patient feedback in the General Practice Patient Survey (GPPS) and Care Quality Commission (CQC) inspections of practices was investigated to understand whether there is an association between patient views and regulator ratings of quality. The specific aims were to understand whether patients' self-reported experiences of primary care can predict CQC inspection ratings of GP practices by: (i) Measuring the association between GPPS results and CQC inspection ratings of GP practices; (ii) Building a predictive model of GP practice quality ratings that use GPPS results; and (iii) Evaluating the predictive model for risk stratification. DESIGN: Retrospective analysis of routinely collected data using decision tree modelling. SETTING: Primary care: GP practices in England. PRIMARY AND SECONDARY OUTCOME MEASURES: GPPS scores and GP practice CQC inspection ratings during 2018. RESULTS: Most GP practices (72%, 974/1350) were rated as 'Good' overall by CQC. Simply assuming that all practices will be rated as 'Good' results in a correct prediction 72% of the time, and it was not possible to improve on this overall level of predictive accuracy using decision tree modelling (correct in 73% of cases). However, a set of GPPS questions were found to have value in identifying practices at elevated risk of a poor inspection rating. CONCLUSIONS: Although there were some associations between GPPS data and CQC inspection ratings, there were limitations to the use of GPPS data for predictive analysis. This is a likely result of the majority of CQC inspections of GPs resulting in a 'Good' or 'Outstanding' rating. However, some GPPS questions were found to have value in identifying practices at higher risk of an 'Inadequate' or 'Requires Improvement' rating, and this may be valuable for surveillance purposes. For example, the CQC could use key questions from the survey to target inspection planning.


Assuntos
Atenção Primária à Saúde , Inglaterra , Humanos , Avaliação de Resultados da Assistência ao Paciente , Qualidade da Assistência à Saúde , Estudos Retrospectivos , Reino Unido
13.
Development ; 147(19)2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32928909

RESUMO

Precise patterning within the three-dimensional context of tissues, organs and embryos implies that cells can sense their relative position. During preimplantation development, outside and inside cells rely on apicobasal polarity and the Hippo pathway to choose their fate. Despite recent findings suggesting that mechanosensing might be central to this process, the relationship between blastomere geometry (i.e. shape and position) and the Hippo pathway effector YAP remains unknown. We used a highly quantitative approach to analyse information on the geometry and YAP localisation of individual blastomeres of mouse and human embryos. We identified the proportion of exposed cell surface area as most closely correlating with the nuclear localisation of YAP. To test this relationship, we developed several hydrogel-based approaches to alter blastomere geometry in cultured embryos. Unbiased clustering analyses of blastomeres from such embryos revealed that this relationship emerged during compaction. Our results therefore pinpoint the time during early embryogenesis when cells acquire the ability to sense changes in geometry and provide a new framework for how cells might integrate signals from different membrane domains to assess their relative position within the embryo.


Assuntos
Blastocisto/citologia , Blastocisto/metabolismo , Blastômeros/metabolismo , Animais , Blastômeros/citologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Feminino , Humanos , Camundongos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
14.
Int J Qual Health Care ; 32(3): 219-220, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32103271

RESUMO

Multiple published studies and reviews have advocated the application of psychometric methods to the validation of patient experience measurement. Some such methods depend on measurement assumptions that may not be appropriate for patient experience. Rather than being the default approach for the validation of patient experience measurement, we argue that psychometric methods should be reviewed critically to determine their fit to the measurement application, and alternative approaches explored, so that the most appropriate validation methods can be identified.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Psicometria/métodos , Humanos , Qualidade da Assistência à Saúde , Inquéritos e Questionários/normas
15.
J Health Serv Res Policy ; 25(3): 151-161, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32056464

RESUMO

OBJECTIVES: Improving patient experience is widely regarded as a key component of health care quality. However, while a considerable amount of data are collected about patient experience, there are concerns this information is not always used to improve care. This study explored whether and how frontline staff use patient experience data for service improvement. METHODS: We conducted a year-long ethnographic case study evaluation, including 299 hours of observations and 95 interviews, of how frontline staff in six medical wards at different hospital sites in the United Kingdom used patient experience data for improvement. RESULTS: In every site, staff undertook quality improvement projects using a range of data sources. Teams of health care practitioners and ancillary staff engaged collectively in a process of sense-making using formal and informal sources of patient experience data. While survey data were popular, 'soft' intelligence - such as patients' stories, informal comments and observations - also informed staff's improvement plans, without always being recognized as data. Teams with staff from different professional backgrounds and grades tended to make more progress than less diverse teams, being able to draw on a wider net of practical, organizational and social resources, support and skills, which we describe as team-based capital. CONCLUSIONS: Organizational recognition, or rejection, of specific forms of patient experience intelligence as 'data' affects whether staff feel the data are actionable. Teams combining a diverse range of staff generated higher levels of 'team-based capital' for quality improvement than those adopting a single disciplinary approach. This may be a key mechanism for achieving person-centred improvement in health care.


Assuntos
Satisfação do Paciente/estatística & dados numéricos , Assistência Centrada no Paciente/organização & administração , Recursos Humanos em Hospital/psicologia , Melhoria de Qualidade/organização & administração , Antropologia Cultural , Atitude do Pessoal de Saúde , Benchmarking/métodos , Inglaterra , Humanos , Assistência Centrada no Paciente/normas , Pesquisa Qualitativa , Melhoria de Qualidade/normas , Qualidade da Assistência à Saúde , Medicina Estatal/organização & administração , Engajamento no Trabalho
16.
Opt Express ; 27(25): 37065-37086, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31873476

RESUMO

The first waveguide coupled phosphide-based UTC photodiodes grown by Solid Source Molecular Beam Epitaxy (SSMBE) are reported in this paper. Metal Organic Vapour Phase Epitaxy (MOVPE) and Gas Source MBE (GSMBE) have long been the predominant growth techniques for the production of high quality InGaAsP materials. The use of SSMBE overcomes the major issue associated with the unintentional diffusion of zinc in MOVPE and gives the benefit of the superior control provided by MBE growth techniques without the costs and the risks of handling toxic gases of GSMBE. The UTC epitaxial structure contains a 300 nm n-InP collection layer and a 300 nm n++-InGaAsP waveguide layer. UTC-PDs integrated with Coplanar Waveguides (CPW) exhibit 3 dB bandwidth greater than 65 GHz and output RF power of 1.1 dBm at 100 GHz. We also demonstrate accurate prediction of the absolute level of power radiated by our antenna integrated UTCs, between 200 GHz and 260 GHz, using 3d full-wave modelling and taking the UTC-to-antenna impedance match into account. Further, we present the first optical 3d full-wave modelling of waveguide UTCs, which provides a detailed insight into the coupling between a lensed optical fibre and the UTC chip.

17.
Sci Rep ; 9(1): 1271, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718644

RESUMO

Staphylococcus pseudintermedius is an opportunistic and emerging zoonotic pathogen that primarily colonises the skin of dogs. Many common variants are methicillin resistant (MRSP) or multidrug resistant (MDR), and drug resistance is increasingly reported across the globe. In New Zealand, MRSP isolation remains rare in clinics. To pre-emptively inform diagnostic and antimicrobial stewardship practices, we examine isolates of S. pseudintermedius, MRSP and MDR-MRSP from New Zealand dogs using a combination of methodologies. Genetic and genomic data combined with antimicrobial susceptibility screening identify common drug-resistance profiles and their genetic determinants. We demonstrate that sensitive and specific species-level identification of S. pseudintermedius can be achieved using Bruker MALDI-TOF MS and, further, that this technique can be used to identify some common subtype variants, providing a level of categorical precision that falls somewhere between single-locus and multi-locus sequence typing. Comparative genomics analysis of global S. pseudintermedius data shows that MRSP moves frequently across the globe, but that horizontal gene transfer events resulting in the acquisition of the SCCmec cassette (responsible for beta-lactam antibiotic resistance) are infrequent. This suggests that biosecurity and surveillance in addition to antibiotic stewardship should play important roles in mitigating the risk of MRSP, especially in countries such as New Zealand where MRSP is still rare.


Assuntos
Doenças do Cão , Farmacorresistência Bacteriana Múltipla , Genômica , Resistência a Meticilina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Infecções Cutâneas Estafilocócicas , Staphylococcus , Animais , Doenças do Cão/genética , Doenças do Cão/metabolismo , Doenças do Cão/microbiologia , Cães , Nova Zelândia , Infecções Cutâneas Estafilocócicas/genética , Infecções Cutâneas Estafilocócicas/metabolismo , Infecções Cutâneas Estafilocócicas/veterinária , Staphylococcus/genética , Staphylococcus/metabolismo
18.
Patient Relat Outcome Meas ; 9: 173-181, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950911

RESUMO

PURPOSE: The Relational Aspects of Care Questionnaire (RAC-Q) is an electronic instrument which has been developed to assess staff's interactions with patients when delivering relational care to inpatients and those accessing accident and emergency (A&E) services. The aim of this study was to reduce the number of questionnaire items and explore scoring methods for "not applicable" response options. PATIENTS AND METHODS: Participants (n=3928) were inpatients or A&E attendees across six participating hospital trusts in England during 2015-2016. The instrument, consisting of 20 questionnaire items, was administered by trained hospital volunteers over a period of 10 months. Items were subjected to exploratory factor analysis to confirm unidimensionality, and the number of items was reduced using a range of a priori psychometric criteria. Two alternative approaches to scoring were undertaken, one treated "not applicable" responses as missing data, while the second adopted a problem score approach where "not applicable" was considered "no problem with care." RESULTS: Two short-form RAC-Qs with alternative scoring options were identified. The first (the RAC-Q-12) contained 12 items, while the second scoring option (the RAC-Q-14) contained 14 items. Scores from both short forms correlated highly with the full 20-item parent form score (RAC-Q-12, r=0.93 and RAC-Q-14, f=0.92), displayed high internal consistency (Cronbach's α: RAC-Q-12=0.92 and RAC-Q-14=0.89) and had high levels of agreement (intraclass correlation coefficient [ICC]=0.97 for both scales). CONCLUSION: The RAC-Q is designed to offer near-real-time feedback on staff's interactions with patients when delivering relational care. The new short-form RAC-Qs and their respective method of scoring are reflective of scores derived using the full 20-item parent form. The new short-form RAC-Qs may be incorporated into inpatient surveys to enable the comparison of ward or hospital performance. Using either the RAC-Q-12 or the RAC-Q-14 offers a method to reduce missing data and response fatigue.

19.
Pharmacoeconomics ; 36(8): 1015-1027, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29797186

RESUMO

OBJECTIVE: To determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active ankylosing spondylitis (AS) who have not responded adequately to previous treatment with conventional care (CC; biologic-naïve population) or previous biologic therapy (biologic-experienced population). PERSPECTIVE AND SETTING: UK National Health Service (NHS). METHODS: The model was structured as a 3-month decision tree leading into a Markov model. Comparators were licensed tumour necrosis factor inhibitors (including available biosimilars) and CC in the biologic-naïve and biologic-experienced populations, respectively. Clinical parameters captured treatment response, short-term disease activity and patient functioning, as well as long-term structural disease progression. Utilities were derived from secukinumab trial data. List prices were used for all drugs. The cost year was 2017 and costs and outcomes were discounted at 3.5%. RESULTS: In the biologic-naïve population, secukinumab dominated adalimumab and certolizumab pegol. Incremental cost-effectiveness ratios (ICERs) versus other comparators were either below £10,000 per quality-adjusted life-year (QALY) gained or south-west ICERs that implied cost effectiveness of secukinumab. In biologic-experienced patients, the ICER for secukinumab versus CC was £4927 per QALY gained. Treatment response rates, short-term treatment effects, long-term radiographic progression and biologic acquisition costs were key model drivers. Scenario analysis found results to be robust to changes in model structural assumptions. Probabilistic analysis identified greater uncertainty in results in the biologic-naïve population. CONCLUSIONS: Even at list price, secukinumab appears to represent a cost-effective use of NHS resources for biologic-naïve and biologic-experienced patients with active AS. Further research on long-term radiographic progression outcomes would be valuable for future cost-effectiveness analyses in AS.


Assuntos
Anticorpos Monoclonais/economia , Análise Custo-Benefício/estatística & dados numéricos , Espondilite Anquilosante/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/uso terapêutico , Custos de Medicamentos/estatística & dados numéricos , Humanos , Cadeias de Markov , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Espondilite Anquilosante/tratamento farmacológico , Reino Unido
20.
Pharmacoeconomics ; 36(7): 867-878, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29797187

RESUMO

OBJECTIVE: The aim was to determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active psoriatic arthritis (PsA) who are tumour necrosis factor inhibitor (TNFi) naïve and without concomitant moderate-to-severe psoriasis, and who have responded inadequately to conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs). PERSPECTIVE AND SETTING: The study took the perspective and setting of the UK National Health Service (NHS). METHODS: The model structure was a 3-month decision tree leading into a Markov model. Separate analyses based on the number of prior csDMARDs (one and two or more) were conducted, with secukinumab 150 mg compared to standard of care (SoC) and TNFis, respectively, for each subpopulation. Clinical parameters, including response at 3 months, were from the FUTURE 2 trial and a network meta-analysis. Outcomes included total costs and quality-adjusted life years (QALYs) over the 40-year time horizon (3.5% annual discount for both outcomes; cost year 2017), and incremental cost effectiveness ratios (ICERs). RESULTS: The ICER for secukinumab 150 mg versus SoC was £28,748 per QALY gained (one prior csDMARD). Secukinumab 150 mg dominated golimumab, certolizumab pegol and etanercept, and had an ICER of £5680 per QALY gained versus adalimumab and > £1 million saved per QALY foregone versus infliximab (two or more prior csDMARDs). Valuing one QALY at between £20,000 and £30,000, the probability of secukinumab having the highest net monetary benefit was 48.9% (one prior csDMARD) and 88.9% (two or more prior csDMARDs). Parameters related to Health Assessment Questionnaire scores were most influential. CONCLUSIONS: Secukinumab 150 mg at list price appears to represent a cost-effective use of NHS resources for adults with PsA who have responded inadequately to one or two or more prior csDMARDs.


Assuntos
Anticorpos Monoclonais/economia , Artrite Psoriásica/economia , Análise Custo-Benefício , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto/economia , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Resistência a Medicamentos , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Reino Unido
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