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BACKGROUND: Mycophenolate is an immunomodulating agent successfully used for the treatment of moderate-to-severe atopic dermatitis (AD) in people. Mycophenolate is an effective steroid-sparing treatment option for use in dogs with inflammatory skin diseases. OBJECTIVE: To evaluate whether once-daily modified-release mycophenolate (OKV-1001) is safe and effective for treating moderate-to-severe canine AD. ANIMALS: Client-owned atopic dogs (n = 9) were enrolled. MATERIALS AND METHODS: In an open-label multicentre pilot study, OKV-1001 (30 mg/kg every 24 h) was given orally for ≤84 days. Concomitant tapering doses of glucocorticoids were administered up to Day (D)28. Clinicians assessed Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) on D0, D14, D28, D56 and D84. Body weight and clinical pathological parameters were measured at baseline and at the end of the study. RESULTS: Treatment with OKV-1001 combined with glucocorticoids significantly reduced the severity of AD within two weeks in seven of nine (77.8%) dogs. The mean percentage change from baseline in the CADESI-04 score was 29% (p = 0.009) at D14 (n = 9), 39% (p = 0.008) at D28 (n = 9) and 49% (p = 0.03) at D56 (n = 7) at which point glucocorticoids had been withdrawn. In two dogs the improvement in CADESI-04 was 62% and 23% (respectively) on D84. No significant adverse events including clinical pathological findings were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Modified-release mycophenolate (OKV-1001) may represent a promising alternative treatment option for dogs with moderate-to-severe AD. The safety and efficacy profile of OKV-1001 will need to be established in larger, placebo-controlled clinical trials.
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Infectious bronchitis virus (IBV) is a highly contagious avian Gammacoronavirus that affects mainly chickens (Gallus gallus) but can circulate in other avian species. IBV constitutes a significant threat to the poultry industry, causing reduced egg yield, growth and mortality levels that can vary in impact. The virus can be transmitted horizontally by inhalation or direct/indirect contact with infected birds or contaminated fomites, vehicles, farm personnel and litter (Figure 1). The error-prone viral polymerase and recombination mechanisms mean diverse viral population results, with multiple genotypes, serotypes, pathotypes and protectotypes. This significantly complicates control and mitigation strategies based on vigilance in biosecurity and the deployment of vaccination.
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Pollos , Infecciones por Coronavirus , Virus de la Bronquitis Infecciosa , Enfermedades de las Aves de Corral , Virus de la Bronquitis Infecciosa/genética , Virus de la Bronquitis Infecciosa/clasificación , Virus de la Bronquitis Infecciosa/fisiología , Animales , Pollos/virología , Enfermedades de las Aves de Corral/virología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/veterinariaRESUMEN
Three days of nitrofurantoin at 100 mg twice daily is recommended as first-line treatment for uncomplicated urinary tract infection (UTI) in evidence-based guidelines across the UK. A review of international guidelines shows that the evidence base has been interpreted in very different ways. UK guidelines are unusual in promoting short (3 day) courses, and we find little direct evidence to support this. Although 'short' courses of antibiotics for other agents may provide optimum balance between providing effective treatment whilst reducing selective pressure driving resistance amongst colonizing microbial flora, it remains unclear that course lengths can be extrapolated to nitrofurantoin. Three days of nitrofurantoin may indeed be a useful intervention in a large group of patients. However, without supporting evidence and because clinical response should be expected to vary widely, it is unclear that establishing and promoting an antibiotic duration for UTI is the best approach to optimizing prescribing in this important area.
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Nitrofurantoína , Infecciones Urinarias , Humanos , Infecciones Urinarias/tratamiento farmacológico , Antibacterianos/uso terapéutico , Resultado del Tratamiento , Reino UnidoRESUMEN
Background: The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods: With the approval of NHS England, we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults.We developed SNOMED-CT codelists for key measures of primary care clinical activity such as blood pressure monitoring and asthma reviews, selected by an expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. Results: We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions: The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data. Funding: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).The OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157).
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COVID-19 , Medicina General , Humanos , Adulto , COVID-19/epidemiología , Estudios Retrospectivos , Pandemias , Inglaterra/epidemiología , Atención Primaria de SaludRESUMEN
This systematic review assessed the state and quality of evidence for effects of gender-affirming hormone therapy on psychosocial functioning. Forty-six relevant journal articles (six qualitative, 21 cross-sectional, 19 prospective cohort) were identified. Gender-affirming hormone therapy was consistently found to reduce depressive symptoms and psychological distress. Evidence for quality of life was inconsistent, with some trends suggesting improvements. There was some evidence of affective changes differing for those on masculinizing versus feminizing hormone therapy. Results for self-mastery effects were ambiguous, with some studies suggesting greater anger expression, particularly among those on masculinizing hormone therapy, but no increase in anger intensity. There were some trends toward positive change in interpersonal functioning. Overall, risk of bias was highly variable between studies. Small samples and lack of adjustment for key confounders limited causal inferences. More high-quality evidence for psychosocial effects of gender-affirming hormone therapy is vital for ensuring health equity for transgender people.
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Personas Transgénero , Humanos , Estudios Prospectivos , Estudios Transversales , Calidad de Vida , Funcionamiento Psicosocial , HormonasRESUMEN
BACKGROUND: The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. AIM: To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication. DESIGN AND SETTING: With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY. METHOD: Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month. RESULTS: Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019). CONCLUSION: Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.
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COVID-19 , Humanos , Femenino , COVID-19/epidemiología , Estudios de Cohortes , Medicina Estatal , Pandemias , Inglaterra/epidemiología , Atención Primaria de SaludRESUMEN
This paper investigated the utility of drone-based environmental monitoring to assist with forest inventory in Queensland private native forests (PNF). The research aimed to build capabilities to carry out forest inventory more efficiently without the need to rely on laborious field assessments. The use of drone-derived images and the subsequent application of digital photogrammetry to obtain information about PNFs are underinvestigated in southeast Queensland vegetation types. In this study, we used image processing to separate individual trees and digital photogrammetry to derive a canopy height model (CHM). The study was supported with tree height data collected in the field for one site. The paper addressed the research question "How well do drone-derived point clouds estimate the height of trees in PNF ecosystems?" The study indicated that a drone with a basic RGB camera can estimate tree height with good confidence. The results can potentially be applied across multiple land tenures and similar forest types. This informs the development of drone-based and remote-sensing image-processing methods, which will lead to improved forest inventories, thereby providing forest managers with recent, accurate, and efficient information on forest resources.
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Ecosistema , Dispositivos Aéreos No Tripulados , Bosques , Árboles , Monitoreo del Ambiente/métodos , Tecnología de Sensores Remotos/métodosRESUMEN
Since the beginning of laboratory medicine, the main focus was to provide high quality analytics. Over time the importance of the extra-analytical phases and their contribution to the overall quality became evident. However, as the initial preanalytical processes take place outside of the laboratory and mostly without its supervision, all professions participating in these process steps, from test selection to sample collection and transport, need to engage accordingly. Focusing solely on intra-laboratory processes will not be sufficient to achieve the best possible preanalytical quality. The Working Group for the Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has provided several recommendations, opinion papers and scientific evidence over the past years, aiming to standardize the preanalytical phase across Europe. One of its strategies to reach this goal are educational efforts. As such, the WG-PRE has organized five conferences in the past decade with the sole focus on preanalytical quality. This year's conference mainly aims to depict the views of different professions on preanalytical processes in order to acquire common ground as basis for further improvements. This article summarizes the content of this 6th preanalytical conference.
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The UK and Europe have seen successive outbreaks of highly pathogenic avian influenza across the 2020/21 and 2021/22 autumn/winter seasons. Understanding both the epidemiology and transmission of these viruses in different species is critical to aid mitigating measures where outbreaks cause extensive mortalities in both land- and waterfowl. Infection of different species can result in mild or asymptomatic outcomes, or acute infections that result in high morbidity and mortality levels. Definition of disease outcome in different species is of great importance to understanding the role different species play in the maintenance and transmission of these pathogens. Further, the infection of species that have conservation value is also important to recognise and characterise to understand the impact on what might be limited wild populations. Highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b has been detected in great skuas (Stercorarius skua) across different colonies on islands off the shore of Scotland, Great Britain during summer 2021. A large number of great skuas were observed as developing severe clinical disease and dying during the epizootic and mortalities were estimated to be high where monitored. Of eight skuas submitted for post-mortem examination, seven were confirmed as being infected with this virus using a range of diagnostic assays. Here we overview the outbreak event that occurred in this species, listed as species of conservation concern in Great Britain and outline the importance of this finding with respect to virus transmission and maintenance.
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Charadriiformes/virología , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/virología , Animales , Animales Salvajes/virología , Brotes de Enfermedades , Subtipo H5N1 del Virus de la Influenza A/clasificación , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Gripe Aviar/epidemiología , Gripe Aviar/mortalidad , Gripe Aviar/transmisión , Escocia/epidemiología , Estaciones del Año , VirulenciaRESUMEN
Low- and middle-income country health systems often apply decontextualised and unrealistic performance targets to facilities. This can lead to empty compliance and 'performing out', whereby managers and providers manipulate or inflate data to create the false impression of a functional system. While this is a well-recognised pitfall of audit-style performance accountability processes, the social processes by which these practices emerge has not been well described in the literature. In this paper, with a focus on maternal and newborn care, we seek to better understand how and why the practices of 'performing out' occur, and their implications for health system functioning, organisational culture, and quality of care. We do this through a focused facility ethnography undertaken in two primary healthcare facilities in an eastern Indian state, anonymised as Esma, where practices of 'performing out' are prevalent. We draw on the understanding that health systems are complex adaptive systems encompassing both hardware and software elements, where individual behavioural practices are an outcome of the system as a whole. To unpack how the dynamic interactions between system elements and agents influence individual behaviours, we draw upon the sociological theories of practice of Bourdieu, encompassing the concepts of field, habitus, and capital. This lens helps illustrate how resource scarcity, unyielding application of unrealistic targets with punitive sanctions for non-achievement, and complex power dynamics lead system actors to manipulate data and create documentation to show the achievement of targets that were not actually met. The practices of 'performing out' are shaped by, and in turn shape, the organisational culture of the facilities, with perverse behaviour becoming part of an entrenched habitus - the 'dispositions' of agents that guide behaviour and thinking. In the longer term, the habituation of 'performing out' contributes to a systemic orientation toward sub-par performance, undermining quality of care.
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Antropología Cultural , Responsabilidad Social , Humanos , Recién Nacido , Cultura Organizacional , Atención Primaria de SaludRESUMEN
Existing performance management approaches in health systems in low-income and middle-income countries are generally ineffective at driving organisational-level and population-level outcomes. They are largely directive: they try to control behaviour using targets, performance monitoring, incentives and answerability to hierarchies. In contrast, enabling approaches aim to leverage intrinsic motivation, foster collective responsibility, and empower teams to self-organise and use data for shared sensemaking and decision-making.The current evidence base is too limited to guide reforms to strengthen performance management in a particular context. Further, existing conceptual frameworks are undertheorised and do not consider the complexity of dynamic, multilevel health systems. As a result, they are not able to guide reforms, particularly on the contextually appropriate balance between directive and enabling approaches. This paper presents a framework that attempts to situate performance management within complex adaptive systems. Building on theoretical and empirical literature across disciplines, it identifies interdependencies between organisational performance management, organisational culture and software, system-level performance management, and the system-derived enabling environment. It uses these interdependencies to identify when more directive or enabling approaches may be more appropriate. The framework is intended to help those working to strengthen performance management to achieve greater effectiveness in organisational and system performance. The paper provides insights from the literature and examples of pitfalls and successes to aid this thinking. The complexity of the framework and the interdependencies it describes reinforce that there is no one-size-fits-all blueprint for performance management, and interventions must be carefully calibrated to the health system context.
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Programas de Gobierno , HumanosRESUMEN
RATIONALE: Social relationships are important in bolstering health and well-being for everyone in the general population. For transgender people, strong supportive social relationships may be paramount to their overall health and well-being due to their marginalised status in society. OBJECTIVE: This review aimed to investigate what is currently known about the social relationship experiences of transgender people and their relational partners (e.g., family members, romantic partners). METHODS: Thirty-nine qualitative papers were extracted from Web of Science, Scopus, Cochrane, and PubMed that related to social relationships of transgender people. These papers were analysed via a qualitative meta-synthesis. RESULTS: Forty-nine second-order themes were identified, initially organised into relational partner clusters (e.g., family, friends, work colleagues) for specific phenomena, then these were synthesized into five overarching conceptual themes: (1) Development of relationships through transition and beyond, (2) Coping strategies of transgender people and their relational partners, (3) Reciprocal support in social relationships, (4) Stigma enacted and ameliorated interpersonally, and (5) Influence of stigma on social health and well-being. DISCUSSION AND CONCLUSIONS: These overarching themes show the potential characteristics that assist in the health-buffering role of social relationships for transgender people and their relational partners. Of particular note, stigma was reported as a common negative experience by transgender people and their relational partners, and open communicative social relationships had positive effects on self-conceptualisations of identity, which were inferred to protect against the damaging effects of stigma. We discuss the various implications and applications of this meta-synthesis to future research and clinical settings as well as how it can inform healthcare policy to support transgender people.
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Personas Transgénero , Adaptación Psicológica , Comunicación , Humanos , Relaciones Interpersonales , Estigma SocialRESUMEN
Global change has resulted in chronic shifts in fire regimes. Variability in the sensitivity of tree communities to multi-decadal changes in fire regimes is critical to anticipating shifts in ecosystem structure and function, yet remains poorly understood. Here, we address the overall effects of fire on tree communities and the factors controlling their sensitivity in 29 sites that experienced multi-decadal alterations in fire frequencies in savanna and forest ecosystems across tropical and temperate regions. Fire had a strong overall effect on tree communities, with an average fire frequency (one fire every three years) reducing stem density by 48% and basal area by 53% after 50 years, relative to unburned plots. The largest changes occurred in savanna ecosystems and in sites with strong wet seasons or strong dry seasons, pointing to fire characteristics and species composition as important. Analyses of functional traits highlighted the impact of fire-driven changes in soil nutrients because frequent burning favoured trees with low biomass nitrogen and phosphorus content, and with more efficient nitrogen acquisition through ectomycorrhizal symbioses. Taken together, the response of trees to altered fire frequencies depends both on climatic and vegetation determinants of fire behaviour and tree growth, and the coupling between fire-driven nutrient losses and plant traits.
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Incendios , Árboles , Ecosistema , Bosques , SueloRESUMEN
A practical and cost-effective destructive sampling method for estimating above and belowground biomass of Corymbia citriodora subspecies variegata grown in plantations is described. The methodology includes details on selecting sample trees, weighing tree components in the field, excavating root systems and obtaining fresh weights and laboratory analyses of components to determine oven dry weights. The development of these sampling procedures is a basic step towards successful, consistent collection of biomass data in 18-20 years old plantation forests. This methodology was developed for eucalypt hardwood timber plantations in Queensland, Australia. However, these procedures can be applied to plantations elsewhere as well as to trees in native forest environments with minor modifications. The methodology developed for field sampling of the tree components and the derivation of allometric relationships for predicting individual tree biomass (above and belowground) highlighted the following:â¢Accurate quantification of above and belowground biomass of eucalypts.â¢Description of measured variables for developing allometric relationships.â¢Integration of field and laboratory measurements to streamline data collection.
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In India, nurses and midwives are key to the provision of public sexual and reproductive health services. Research on impediments to their performance has primarily focused on their individual capability and systemic resource constraints. Despite emerging evidence on gender-based discrimination and low professional acceptance faced by these cadres, little has been done to link these constraints to power asymmetries within the health system. We analysed data from an ethnography conducted in two primary healthcare facilities in an eastern state in India, using Veneklasen and Miller's expressions of power framework, to explore how power and gender asymmetries constrain performance and quality of care provided by Auxiliary Nurse Midwives (ANMs). We find that ANMs' low position within the official hierarchy allows managers and doctors to exercise "power over" them, severely curtailing their expression of all other forms of power. Disempowerment of ANMs occurs at multiple levels in interlinked and interdependent ways. Our findings contribute to the empirical evidence, advancing the understanding of gender as a structurally embedded dimension of power. We illustrate how the weak positioning of ANMs reflects their lack of representation in policymaking positions, a virtual absence of gender-sensitive policies, and ultimately organisational power structures embedded in patriarchy. By deepening the understanding of empowerment, the paper suggests implementable pathways to empower ANMs for improved performance. This requires addressing entrenched gender inequities through structural and organisational changes that realign power relations, facilitate more collaborative ways of exercising power, and create the antecedents to individual empowerment.
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Partería , Enfermeras Obstetrices , Médicos , Femenino , Humanos , India , EmbarazoRESUMEN
We describe the optimisation of a simplified sample preparation method which permits rapid and direct detection of SARS-CoV-2 RNA within saliva, using reverse-transcription loop-mediated isothermal amplification (RT-LAMP). Treatment of saliva samples prior to RT-LAMP by dilution 1:1 in Mucolyse™, followed by dilution in 10 % (w/v) Chelex© 100 Resin and a 98⯰C heat step for 2â¯min enabled detection of SARS-CoV-2 RNA in positive saliva samples. Using RT-LAMP, SARS-CoV-2 RNA was detected in as little as 05:43â¯min, with no amplification detected in 3097 real-time reverse transcription PCR (rRT-PCR) negative saliva samples from staff tested within a service evaluation study, or for other respiratory pathogens tested (nâ¯=â¯22). Saliva samples can be collected non-invasively, without the need for skilled staff and can be obtained from both healthcare and home settings. Critically, this approach overcomes the requirement for, and validation of, different swabs and the global bottleneck in obtaining access to extraction robots and reagents to enable molecular testing by rRT-PCR. Such testing opens the possibility of public health approaches for effective intervention during the COVID-19 pandemic through regular SARS-CoV-2 testing at a population scale, combined with isolation and contact tracing.