RESUMO
Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.
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Lesão Pulmonar , Síndrome do Desconforto Respiratório , Animais , Humanos , Hipóxia/etiologia , Inflamação/complicações , Pulmão , Lesão Pulmonar/complicações , CamundongosRESUMO
PURPOSE: To develop guidance for the selection of balloon catheter size when performing an oesophageal dilatation for a stricture post oesophageal atresia repair. METHODS: This was a single centre retrospective study at a paediatric tertiary centre. Dilatations were performed between 2015 and 2020. All dilatations were performed under general anaesthesia using balloon catheters under fluoroscopic guidance. Outliers were excluded using ROUT method and descriptive analysis was calculated to 1SD or IQR depending on the normality of data distribution. RESULTS: 97 patients underwent 341 dilatations. Median age was 19 months (37 weeks corrected gestation-17 years), median weight was 10.7 kg (2.6-72 kg). Balloon catheter sizes ranged from 6-8 mm to 18-20 mm. There was strong correlation between weight and balloon size (r = 0.8, p < 0.0001). There were 2 perforations (0.6%), both diagnosed intra-operatively and treated conservatively. From the results, weight recommendations were created for each balloon size. CONCLUSION: Fluoroscopic balloon dilatation is a safe and effective method to treat anastomotic stricture following oesophageal atresia repair. Previous studies have shown correlation between patient weight and oesophageal diameter. We propose guidance for using an appropriate balloon size based on patient's weight with the aim to reduce complication.
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Atresia Esofágica , Criança , Humanos , Lactente , Atresia Esofágica/cirurgia , Dilatação , Constrição Patológica , Estudos Retrospectivos , FluoroscopiaRESUMO
The incidence of chronic kidney disease is increasing internationally with many risk factors for chronic kidney disease also being risk factors for type 2 diabetes. Nurses should use primary, secondary and tertiary prevention to minimise the incidence of chronic kidney disease when caring for individuals with type 2 diabetes. This article is the second in a two-part series on the interrelationship between these long-term conditions. Part 1 addressed the significance of using primary prevention to promote kidney health in adults living with type 2 diabetes; part 2 will discuss the use of secondary and tertiary prevention relevant to these long-term conditions.
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Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , RimRESUMO
The incidence of chronic kidney disease is increasing internationally with risk factors for the condition being the same as those for type 2 diabetes. It is important therefore for nurses to use primary, secondary and tertiary prevention to minimise the incidence of chronic kidney disease when caring for individuals with type 2 diabetes. This article is the first of a two-part series on the interrelationship between these long-term conditions. This article, part 1, addresses the significance of primary prevention in promoting kidney health in adults living with type 2 diabetes, while part 2 will discuss the use of secondary and tertiary prevention relevant to these long-term conditions.
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Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Incidência , RimRESUMO
BACKGROUND: The EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential. The IATA is structured in tiers, allowing grouping decisions to be made using simple in vitro or in silico methods in Tier1 progressing to in vivo approaches at the highest Tier3. Here we present a case-study testing the applicability of GRACIOUS IATA to form an evidence-based group of multiwalled carbon nanotubes (MWCNT) posing a similar predicted fibre-hazard, to support read-across and reduce the burden of toxicity testing. RESULTS: The case-study uses data on 15 different MWCNT, obtained from the published literature. By following the IATA, a group of 2 MWCNT was identified (NRCWE006 and NM-401) based on a high degree of similarity. A pairwise similarity assessment was subsequently conducted between the grouped MWCNT to evaluate the potential to conduct read-across and fill data gaps required for regulatory hazard assessment. The similarity assessment, based on expert judgement of Tier 1 assay results, predicts both MWCNT are likely to cause a similar acute in vivo hazard. This result supports the possibility for read-across of sub-chronic and chronic hazard endpoint data for lung fibrosis and carcinogenicity between the 2 grouped MWCNT. The implications of accepting the similarity assessment based on expert judgement of the MWCNT group are considered to stimulate future discussion on the level of similarity between group members considered sufficient to allow regulatory acceptance of a read-across argument. CONCLUSION: This proof-of-concept case-study demonstrates how a grouping hypothesis and IATA may be used to support a nuanced and evidence-based grouping of 'similar' MWCNT and the subsequent interpolation of data between group members to streamline the hazard assessment process.
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Nanotubos de Carbono , Fibrose Pulmonar , Administração por Inalação , Humanos , Pulmão , Nanotubos de Carbono/toxicidade , Testes de Toxicidade/métodosRESUMO
The incorporation of nanomaterials (NMs) in consumer products has proven to be highly valuable in many sectors. Unfortunately, however, the same nano specific physicochemical properties, which make these material attractive, might also contribute to hazards for people exposed to these materials. The physicochemical properties of NMs will impact their interaction with biological surroundings and influence their fate and their potential adverse effects such as genotoxicity. Due to the large and expanding number of NMs produced, their availability in different nanoforms (NFs) and their utilization in various formats, it is impossible for risk assessment to be conducted on an individual NF basis. Alternative methods, such as grouping are needed for streamlining hazard assessment. The GRACIOUS Framework provides a logical and science evidenced approach to group similar NFs, allowing read-across of hazard information from source NFs (or non-NFs) with adequate hazard data to target NFs that lack such data. Here, we propose a simple three-tiered testing strategy to gather evidence to determine whether different NFs are sufficiently similar with respect to their potential to induce genotoxicity, in order to be grouped. The tiered testing strategy includes simple in vitro models as well as a number of alternative more complex multi-cellular in vitro models to allow for a better understanding of secondary NM-induced DNA damage, something that has been more appropriate in vivo until recently.
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Nanoestruturas , Dano ao DNA , Humanos , Nanoestruturas/química , Nanoestruturas/toxicidade , Medição de Risco/métodosRESUMO
BACKGROUND: Nanomaterials can exist in different nanoforms (NFs). Their grouping may be supported by the formulation of hypotheses which can be interrogated via integrated approaches to testing and assessment (IATA). IATAs are decision trees that guide the user through tiered testing strategies (TTS) to collect the required evidence needed to accept or reject a grouping hypothesis. In the present paper, we investigated the applicability of IATAs for ingested NFs using a case study that includes different silicon dioxide, SiO2 NFs. Two oral grouping hypotheses addressing local and systemic toxicity were identified relevant for the grouping of these NFs and verified through the application of oral IATAs. Following different Tier 1 and/or Tier 2 in vitro methods of the TTS (i.e., in vitro dissolution, barrier integrity and inflammation assays), we generated the NF datasets. Furthermore, similarity algorithms (e.g., Bayesian method and Cluster analysis) were utilized to identify similarities among the NFs and establish a provisional group(s). The grouping based on Tier 1 and/or Tier 2 testing was analyzed in relation to available Tier 3 in vivo data in order to verify if the read-across was possible and therefore support a grouping decision. RESULTS: The measurement of the dissolution rate of the silica NFs in the oro-gastrointestinal tract and in the lysosome identified them as gradually dissolving and biopersistent NFs. For the local toxicity to intestinal epithelium (e.g. cytotoxicity, membrane integrity and inflammation), the biological results of the gastrointestinal tract models indicate that all of the silica NFs were similar with respect to the lack of local toxicity and, therefore, belong to the same group; in vivo data (although limited) confirmed the lack of local toxicity of NFs. For systemic toxicity, Tier 1 data did not identify similarity across the NFs, with results across different decision nodes being inconsistent in providing homogeneous group(s). Moreover, the available Tier 3 in vivo data were also insufficient to support decisions based upon the obtained in vitro results and relating to the toxicity of the tested NFs. CONCLUSIONS: The information generated by the tested oral IATAs can be effectively used for similarity assessment to support a grouping decision upon the application of a hypothesis related to toxicity in the gastrointestinal tract. The IATAs facilitated a structured data analysis and, by means of the expert's interpretation, supported read-across with the available in vivo data. The IATAs also supported the users in decision making, for example, reducing the testing when the grouping was well supported by the evidence and/or moving forward to advanced testing (e.g., the use of more suitable cellular models or chronic exposure) to improve the confidence level of the data and obtain more focused information.
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Nanoestruturas , Dióxido de Silício , Humanos , Dióxido de Silício/toxicidade , Teorema de Bayes , Nanoestruturas/toxicidade , Medição de Risco , InflamaçãoRESUMO
INTRODUCTION: It is purported that patients with peripheral arterial disease (PAD) may have impaired cognitive function due to concomitant cerebrovascular disease. Such disease may be clinically unrecognized but can impact on a patient's recovery and prognosis. The purpose of this systematic review was to interrogate the body of published evidence on undiagnosed cognitive impairment in PAD patients. METHODS: A search strategy encompassing MEDLINE, Scopus, and the Cochrane database was developed to identify peer-reviewed articles examining rates of undiagnosed cognitive impairment in patients with PAD. The following search terms were used: 'PAD'; 'PVD'; 'dementia'; 'peripheral arterial disease'; 'peripheral vascular disease'; 'cognitive impairment'; 'alzheimer's disease' and 'cogniti∗'. Our primary outcome was the incidence of previously undiagnosed cognitive impairment in patients with PAD. RESULTS: The initial search yielded 1492 titles. After removal of duplicates, 961 abstracts were screened to ascertain if they were eligible for inclusion. Abstract review yielded 62 full texts for further evaluation. Eight case-control studies consisting of 1161 patients were included. Analysis of these studies revealed that PAD patients performed significantly worse than controls on a variety of neuropsychological measures. CONCLUSION: Our review indicated that PAD patients are more likely to suffer with undiagnosed cognitive impairment than healthy controls.
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Doença de Alzheimer , Disfunção Cognitiva , Doença Arterial Periférica , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Cognição , Disfunção Cognitiva/complicações , Disfunção Cognitiva/etiologia , Humanos , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnósticoRESUMO
Improved strategies are required for testing nanomaterials (NMs) to make hazard and risk assessment more efficient and sustainable. Including reduced reliance on animal models, without decreasing the level of human health protection. Acellular detection of reactive oxygen species (ROS) may be useful as a screening assay to prioritize NMs of high concern. To improve reliability and reproducibility, and minimize uncertainty, a standard operating procedure (SOP) has been developed for the detection of ROS using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH2-DA) assay. The SOP has undergone an inter- and intra-laboratory comparison, to evaluate robustness, reliability, and reproducibility, using representative materials (ZnO, CuO, Mn2O3, and BaSO4 NMs), and a number of calibration tools to normalize data. The SOP includes an NM positive control (nanoparticle carbon black (NPCB)), a chemical positive control (SIN-1), and a standard curve of fluorescein fluorescence. The interlaboratory comparison demonstrated that arbitrary fluorescence units show high levels of partner variability; however, data normalization improved variability. With statistical analysis, it was shown that the SIN-1 positive control provided an extremely high level of reliability and reproducibility as a positive control and as a normalization tool. The NPCB positive control can be used with a relatively high level of reproducibility, and in terms of the representative materials, the reproducibility CuO induced-effects was better than for Mn2O3. Using this DCFH2-DA acellular assay SOP resulted in a robust intra-laboratory reproduction of ROS measurements from all NMs tested, while effective reproduction across different laboratories was also demonstrated; the effectiveness of attaining reproducibility within the interlaboratory assessment was particle-type-specific.
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Nanopartículas , Nanoestruturas , Animais , Bioensaio , Nanoestruturas/toxicidade , Espécies Reativas de Oxigênio , Reprodutibilidade dos TestesRESUMO
Arthrodesis of the first metatarsal phalangeal joint (MTPJ) is a widely utilized surgical procedure for a wide array of metatarsal pathologies. This study aims to explore the functional limitations following first MTPJ arthrodesis, overall satisfaction and patient's abilities to achieve activities of daily living (ADL). This prospective cohort study assessed functional limitations as well as footwear and lifestyle restrictions using several questionnaires. One hundred and three participants who had a first MTPJ arthrodesis under the care of a single surgeon were recruited. Pre- and postoperative patient-reported outcome measures were recorded. The American Orthopaedic Foot and Ankle Score (AOFAS) and the Manchester-Oxford Foot Questionnaire were also used to further examine functional status. Hallux valgus angle (HVA) and intermetatarsal angle (IMA) were compared using preoperative and postoperative weightbearing radiographs and successful fusion was recorded. Complications were documented and are discussed in detail. The duration of follow-up was more than 12 months. There was one nonunion in the cohort while 2 patients experienced delay to fusion. Approximately 97% of patients were very satisfied with the procedure and their ability to achieve ADLs post operatively. A further 82.5% of patients were able to return to wearing nonadaptive footwear. The mean reduction in HVA and IMA was 21.78° and 6.84°, respectively. This study demonstrates the safe and successful use of a compression screw/locking plate construct for arthrodesis of the first MTPJ. Furthermore, the study provides clear evidence of high levels of functionality after the procedure with statistically significant differences (p value <.05) in all 4 facets of the AOFAS questionnaire as well as several notable differences in activity levels and footwear restrictions pre and postoperatively.
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Hallux Valgus , Ossos do Metatarso , Articulação Metatarsofalângica , Atividades Cotidianas , Artrodese , Parafusos Ósseos , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Articulação Metatarsofalângica/diagnóstico por imagem , Articulação Metatarsofalângica/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: This commentary aims to describe a case of how meaningful co-design between rural health service leaders and a health service-embedded research unit can identify emerging research priorities and optimise translation. CONTEXT: The challenges facing rural health services are unique, and the important role of health service leaders in the research response is increasingly recognised. Poorly-designed research can contribute to research waste through reduced applicability of results to rural communities, and an opportunity exists to increase research co-designed with rural health services through the involvement of research users during study planning. APPROACH: In early 2020, leaders at a rural Victorian health service approached the embedded health service research unit to request research be conducted on an emerging issue: rural staff well-being in the face of the COVID-19 pandemic. This was based on their concern regarding the lack of available COVID-19-specific evidence to inform organisational policy. In collaboration with the rural health service executive, a translation-focused study of staff well-being with nine rural Victorian health services was developed. Key co-design activities of the project included involving research end-users as study investigators and conducting formal stakeholder engagement regarding study design and outcomes. CONCLUSION: Meaningful co-design of research with health services is a multifaceted process that can assist researchers and end-users alike in identifying and responding to emerging health issues. In the rural setting where there is a vital need for impactful health research, we recommend that researchers should consider employing co-design processes in order to minimise research waste and optimise the translatability of research findings.
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COVID-19 , Serviços de Saúde Rural , Humanos , Pandemias , População RuralRESUMO
Rationale: Acute respiratory distress syndrome is defined by the presence of systemic hypoxia and consequent on disordered neutrophilic inflammation. Local mechanisms limiting the duration and magnitude of this neutrophilic response remain poorly understood. Objectives: To test the hypothesis that during acute lung inflammation tissue production of proresolution type 2 cytokines (IL-4 and IL-13) dampens the proinflammatory effects of hypoxia through suppression of HIF-1α (hypoxia-inducible factor-1α)-mediated neutrophil adaptation, resulting in resolution of lung injury. Methods: Neutrophil activation of IL4Ra (IL-4 receptor α) signaling pathways was explored ex vivo in human acute respiratory distress syndrome patient samples, in vitro after the culture of human peripheral blood neutrophils with recombinant IL-4 under conditions of hypoxia, and in vivo through the study of IL4Ra-deficient neutrophils in competitive chimera models and wild-type mice treated with IL-4. Measurements and Main Results: IL-4 was elevated in human BAL from patients with acute respiratory distress syndrome, and its receptor was identified on patient blood neutrophils. Treatment of human neutrophils with IL-4 suppressed HIF-1α-dependent hypoxic survival and limited proinflammatory transcriptional responses. Increased neutrophil apoptosis in hypoxia, also observed with IL-13, required active STAT signaling, and was dependent on expression of the oxygen-sensing prolyl hydroxylase PHD2. In vivo, IL-4Ra-deficient neutrophils had a survival advantage within a hypoxic inflamed niche; in contrast, inflamed lung treatment with IL-4 accelerated resolution through increased neutrophil apoptosis. Conclusions: We describe an important interaction whereby IL4Rα-dependent type 2 cytokine signaling can directly inhibit hypoxic neutrophil survival in tissues and promote resolution of neutrophil-mediated acute lung injury.
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Lesão Pulmonar Aguda/imunologia , Subunidade alfa de Receptor de Interleucina-4/imunologia , Interleucina-4/imunologia , Neutrófilos/imunologia , Receptores de Superfície Celular/imunologia , Síndrome do Desconforto Respiratório/imunologia , Lesão Pulmonar Aguda/metabolismo , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular/imunologia , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Subunidade alfa de Receptor de Interleucina-4/genética , Subunidade alfa de Receptor de Interleucina-4/metabolismo , Camundongos , Camundongos Knockout , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Receptores de Superfície Celular/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Admission to an emergency department (ED) may expose the older person with dementia to a range of negative consequences, including a deterioration in their behavioural symptoms. The authors conducted a review of primary research relating to the experiences of older people with dementia, their carers and ED nurses, to understand how these experiences might inform nursing practice. METHODS: Integrative review with a search of the electronic databases of Medline, CINAHL and PSYCHINFO using specified inclusion and exclusion criteria. RESULTS: Three themes were identified: carers and older people with dementia-waiting and worrying; nurses juggling priorities; and strategies for improvement-taking a partnership approach. CONCLUSION: Older people with dementia may be exposed to disparities in treatment in the ED. A practice partnership between carers and ED nurses may help to prevent this. ED nurses need support to blend technical- and relationship-centred care. Participatory research exploring the experiences of older people with dementia, their carers and ED nurses is needed.
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Demência , Serviço Hospitalar de Emergência , Idoso , Idoso de 80 Anos ou mais , Cuidadores , HumanosRESUMO
BACKGROUND: Nursing process quality care metrics and indicators are quantifiable measures of the nursing care delivered to clients. They can be used to identify and support nurses' contribution to high quality, safe, client care and are lacking in specialist intellectual disability nursing. In a national Nursing Quality Care-Metrics project for Irish intellectual disability services, a set of nursing quality care process metrics and associated indicators were established for intellectual disability services. METHODS: A two-stage design approach was undertaken; a broad scoping review of the literature and a modified Delphi consensus process. The Delphi included a four round e-Delphi survey and a consensus meeting. Four hundred one intellectual disability nurses working in Ireland were recruited for the surveys and 20 stakeholders attended the consensus meeting. RESULTS: From the review, 20 existing and 16 potential intellectual disability nursing metrics were identified for nurses to prioritise in the e-surveys. After the four survey rounds, 12 intellectual disability nursing metrics and 84 associated indicators were identified. Following the consensus meeting, these were reduced to 12 metrics and 79 indicators. CONCLUSIONS: This first set of intellectual disability nursing process metrics and associated indicators has been identified for implementation in practice. These metrics while developed in Ireland have international relevance and their application and appropriateness in practice needs to be evaluated.
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Deficiência Intelectual/enfermagem , Processo de Enfermagem , Indicadores de Qualidade em Assistência à Saúde/organização & administração , Qualidade da Assistência à Saúde/organização & administração , Consenso , Técnica Delphi , HumanosRESUMO
AIM: To develop a suite of nursing quality care process metrics and indicators for older persons care settings in Ireland. BACKGROUND: Regulatory investigations of health system failures highlight non-adherence to clinical guidelines and standards resulting in deficiencies in nursing care delivery. Limited attention has been paid to measuring nursing care processes particularly in the care of older people. Quality care process metrics can facilitate measurement of nurse-sensitive measures of care. DESIGN: A scoping literature review and modified Delphi-Consensus Technique. METHODS: A scoping review of literature published between January 2007 - January 2017 was conducted to identify nursing process metrics and indicators. The Delphi Consensus phase incorporated a four-round electronic survey of 404 nurses and a consensus meeting with 13 stakeholders working in Older Persons Care Settings in Ireland. FINDINGS: From the review, 33 potential metrics were identified. After all Delphi survey rounds, 20 metrics and 90 associated indicators were selected by the nurses. Following the consensus meeting, 19 metrics and 80 indicators were included in the final suite of nursing quality care process metrics and indicators. CONCLUSION: Developing this suite of nursing quality care process metrics and indicators for use in older persons care settings provided consensus on what nursing processes should be measured to improve the quality and safety of care delivery. IMPACT: The nursing processes identified, provide a framework for future research and educational programmes in the care of older persons. Although conducted in the Irish healthcare system, there is potential for adoption or adaption in other healthcare settings.
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Técnica Delphi , Serviços de Saúde para Idosos/organização & administração , Qualidade da Assistência à Saúde , Idoso , HumanosRESUMO
AIMS AND OBJECTIVES: To generate insights about what matters and is valued by family members of older people with dementia in the emergency department. To explore the experiences of emergency nurses looking after older people with dementia in an episode of care. BACKGROUND: In the emergency department, older people with dementia are at risk of suboptimal care. Little is known of the experiences of family members of being with an older person with dementia in the emergency department or the experiences of emergency nurses looking after older people with dementia in this environment. DESIGN AND METHODS: Phase 1 Data Analysis of the Discovery Phase of an Appreciative Inquiry study. Study participants were family members of older people with dementia and emergency nurses. Data collection methods included interviews with family members of older people with dementia and 30 hr of participant observation working alongside emergency nurses. This study was guided by the Standards for Reporting Qualitative Research. RESULTS: Two themes emerged from the analysis: What matters to family members with four subthemes and challenges for family members and nurses in the emergency department with two subthemes. CONCLUSION: This study demonstrates that some emergency nurses are connecting with family members even in the briefest of clinical encounters. It is feasible for more emergency nurses to do the same more of the time. RELEVANCE TO CLINICAL PRACTICE: The older person with dementia must be given a triage category of no less than 3 (to be seen by the doctor within the hour) on arrival in the department. Further education is needed to assist emergency nurses to establish rapport and incorporate family member insights as part of care planning and assessment of the needs of the older person with dementia.
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Demência/enfermagem , Enfermagem em Emergência/métodos , Serviço Hospitalar de Emergência/normas , Família/psicologia , Relações Profissional-Família , Idoso , Feminino , Humanos , Masculino , Pesquisa QualitativaRESUMO
The first definitive hematopoietic stem cells (dHSCs) in the mouse emerge in the dorsal aorta of the embryonic day (E) 10.5 to 11 aorta-gonad-mesonephros (AGM) region. Notch signaling is essential for early HSC development but is dispensable for the maintenance of adult bone marrow HSCs. How Notch signaling regulates HSC formation in the embryo is poorly understood. We demonstrate here that Notch signaling is active in E10.5 HSC precursors and involves both Notch1 and Notch2 receptors, but is gradually downregulated while they progress toward dHSCs at E11.5. This downregulation is accompanied by gradual functional loss of Notch dependency. Thus, as early as at final steps in the AGM region, HSCs begin acquiring the Notch independency characteristic of adult bone marrow HSCs as part of the maturation program. Our data indicate that fine stage-dependent tuning of Notch signaling may be required for the generation of definitive HSCs from pluripotent cells.
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Aorta/embriologia , Embrião de Mamíferos/citologia , Gônadas/embriologia , Células-Tronco Hematopoéticas/citologia , Mesonefro/embriologia , Receptor Notch2/metabolismo , Células Estromais/citologia , Animais , Aorta/metabolismo , Células Cultivadas , Embrião de Mamíferos/metabolismo , Gônadas/metabolismo , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Mesonefro/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais , Células Estromais/metabolismoRESUMO
BACKGROUND: Oropharyngeal dysphagia post-stroke is well known, with its presence increasing the risk of poor outcomes in particular aspiration and aspiration pneumonia. Management to minimize the risk of aspiration and improve swallow safety post-stroke includes the treatment of thickened liquids (TL), an established bolus modification intervention. Despite widespread use, there is a lack of robust empirical evidence and minimal patient evidence as to the experience and acceptability of using thickeners by people who experience dysphagia after a stroke. AIMS: To explore people with swallowing disorders post-stroke experiences of and acceptability regarding the bolus modification treatment of thickened liquids. METHODS & PROCEDURES: A qualitative, descriptive study exploring the experiences of individuals given TL after their stroke. A purposive sample of 14 adults was obtained with data collection and generation through the medium of individual semi-structured interviews. Inductive thematic analysis was used to analyse the data. OUTCOMES & RESULTS: Three overarching themes of 'uncertainty', 'an unpleasant experience' and 'a trade-off' were identified. These themes highlight that participants disliked TL and this dislike may have impacted clinically in terms of adherence, hydration and quality of life. Lack of sensory appeal was important in framing patient dislike. Participants' involvement in and understanding of reasons for prescription of TL was poor leading to uncertainty regarding the treatment. Notwithstanding, some participants felt it was necessary for their stroke recovery. CONCLUSIONS & IMPLICATIONS: TL can be considered a burdensome treatment from multiple perspectives including product palatability, treatment uncertainty and treatment adherence issues. Despite intensely disliking this treatment, some patients ultimately understand why the treatment is prescribed. Improvements in product palatability are required in order to improve adherence and patient quality of life. Consideration of other treatment options and newer products to manage aspiration post-stroke is also warranted.
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Transtornos de Deglutição/psicologia , Comportamento de Ingestão de Líquido , Acidente Vascular Cerebral/psicologia , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , ViscosidadeRESUMO
Glucose-6-phosphate dehydrogenase deficiency affects approximately 400 million people worldwide and is an X-linked disorder most commonly found in individuals of African, Asian, Mediterranean, and Middle Eastern descent. It can present with acute hemolysis in response to certain drugs, infections, or fava beans, and affected individuals may not be aware that they have glucose-6-phosphate dehydrogenase deficiency. This case illustrates the importance of those working in the acute and urgent care sector having an awareness of the condition and the value of a full set of vital signs in an unwell child.