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We investigated whether cement pastes are a possible source of ecotoxicologically potent substances. For this purpose, leaching according to DIN EN 16637-2 was performed on portland cement pastes as well as blast furnace slag cement with and without an air entraining agent (AEA). The AEA, consisting of wood rosin and resin, contained the stabiliser drometrizole and the biocide octylisothiazolinone (OIT), which was confirmed by our non-target screening (NTS). Our ecotoxicological studies (Daphnia magna, Aliivibrio fischeri and Desmodesmus subspicatus) of the pure cement eluates showed no effects at all. In these samples, it was possible to attribute up to 85 % of the dissolved organic carbon (DOC) to acetate, formate and diethylene glycol (DiEG). Eluates from cement pastes with AEA contained up to 70 µg/L octylisothiazolinone (OIT), and no drometrizole was found. Around 90 % of the total OIT release happened within the first 6 h. It was possible to attribute the observed ecotoxicological effects mainly to the OIT concentrations. Additional leaching with elevated sulphate concentrations (800 mg/L) did not influence the release of DOC and OIT or increase the ecotoxicological effects. As a consequence, we advise curing the cement paste for 24 h prior to use, as this largely avoids the release of OIT and the observed ecotoxicological effects.
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INTRODUCTION: Evidence-based practice (EBP) is essential for ensuring the delivery of effective and efficient healthcare. Despite this, EBP is not always well implemented in the clinical environment. Evidence suggests that the application of EBP is likely impacted by healthcare workers' attitudes, knowledge and skills. While there has been a recent proliferation of international research examining diagnostic radiographers' attitudes towards, knowledge of and skills in EBP, no such research exists in an Australian context. METHODS: This study presents the results of a validated self-report survey, the evidence-based practice questionnaire (EBPQ), administered to Australian diagnostic radiographers. The data were described and aggregated means were calculated for each of the domains. Inferential statistical tests were computed, including Cronbach's alpha, Pearson's correlations and independent t-tests, and Kruskal-Wallis tests. RESULTS: The aggregated mean for the practice domain was 5.02 (SD 1.104), for the attitudes domain it was 5.41 (SD 1.169), and for the knowledge and skills domain, it was 5.20 (SD 1.177) on a seven-point scale. Significant associations were identified among these domains, with individuals holding higher qualifications and occupying leadership positions more likely to score higher. Additionally, the modality in which an individual primarily practiced appeared to also have an impact on their score. However, no significant correlation was found between any domain and the number of years an individual had been practicing. CONCLUSION: This research has established a baseline of Australian diagnostic radiographers' practices, knowledge skills and attitudes towards evidence-based practice. IMPLICATIONS FOR PRACTICE: This baseline can inform the development of interventions aimed at enhancing the role of evidence-based practice in the sampled population.
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Prática Clínica Baseada em Evidências , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Autorrelato , Austrália , Inquéritos e QuestionáriosRESUMO
Animals frequently make adaptive decisions about what to prioritize when faced with multiple, competing demands simultaneously. However, the proximate mechanisms of decision-making in the face of competing demands are not well understood. We explored this question using brain transcriptomics in a classic model system: threespined sticklebacks, where males face conflict between courtship and territorial defence. We characterized the behaviour and brain gene expression profiles of males confronted by a trade-off between courtship and territorial defence by comparing them to males not confronted by this trade-off. When faced with the trade-off, males behaviourally prioritized defence over courtship, and this decision was reflected in their brain gene expression profiles. A distinct set of genes and biological processes was recruited in the brain when males faced a trade-off and these responses were largely non-overlapping across two brain regions. Combined, these results raise new questions about the interplay between the neural and molecular mechanisms involved in decision-making.
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Smegmamorpha , Animais , Masculino , Smegmamorpha/genética , Territorialidade , Perfilação da Expressão GênicaRESUMO
Background: We report the radiological and functional outcomes at five years in patients with severe osteoarthritis of the glenohumeral joint and a Walch type B glenoid who have undergone stemless anatomic total shoulder replacement. Methods: A retrospective analysis of case notes, computed tomography scans and plain radiographs of patients undergoing anatomic total shoulder replacement for primary glenohumeral osteoarthritis were performed. Patients were grouped by the severity of their osteoarthritis using the modified Walch classification, glenoid retroversion and posterior humeral head subluxation. An evaluation was made using modern planning software. Functional outcomes were assessed using the American shoulder and elbow surgeons score, shoulder pain and disability index and visual analogue scale. Annual Lazarus scores were reviewed as regard to glenoid loosening. Results: Thirty patients were reviewed at 5 years. Analysis of all patient-reported outcome measures demonstrated significant improvement at 5-year review, American shoulder and elbow surgeons (p = <0.0001), shoulder pain and disability index (p = 0.0001), visual analogue scale (p = 0.0001). Radiological associations between Walch scores and Lazarus scores were not statistically significant (p = 0.1251) at 5 years. There were no associations between features of glenohumeral osteoarthritis and patient-reported outcome measures. Discussion: The severity of osteoarthritis did not show any association with glenoid component survivorship or with patient-reported outcome measures at 5 years review. Level of evidence: IV.
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AIMS: To investigate the frequency of carriage of methicillin-susceptible and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in a population of clinically normal dogs within the Christchurch and wider Canterbury region, an area in which MRSP has been detected. METHODS: Buccal and perianal swabs were collected from 126 clinically normal dogs presenting at veterinary clinics in the Christchurch/Canterbury region for de-sexing or routine vaccination. S. pseudintermedius was isolated by selective culture. Isolates were tested for susceptibility to 12 antimicrobials by disc diffusion. RESULTS: S. pseudintermedius was isolated from 92/126 (73.0 (95% CI = 64.4-80.5)%) dogs, with 38/126 (30.2 (95% CI = 22.3-39.0)%) positive dogs carrying S. pseudintermedius at both sampled sites. More animals (78/126; 61.9 (95% CI = 52.8-70.4)%) had positive mouth cultures than positive perianal region cultures (52/126; 41.3 (95% CI = 32.6-50.4)%). No MRSP was isolated from clinically normal dogs. However, resistance to penicillin (106/130 (85.1%) swabs) and tetracycline (33/130 (25.4%) swabs) was seen. CONCLUSIONS: The majority of the dogs in this sample were carriers of S. pseudintermedius. However, none of these isolates were MRSP. CLINICAL RELEVANCE: While most clinically normal dogs in the studied region are likely to be carriers of S. pseudintermedius, only a small proportion, if any, are likely to be carriers of MRSP. Antibiotic stewardship practices may be important to maintain low-level circulation of drug-resistant bacterial lineages.
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Doenças do Cão , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Cães , Animais , Resistência a Meticilina , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/microbiologia , Nova Zelândia/epidemiologia , Antibacterianos/farmacologia , Doenças do Cão/epidemiologia , Doenças do Cão/microbiologia , Testes de Sensibilidade Microbiana/veterináriaRESUMO
Resilience can be defined as the ability of an animal to remain productive in the face of diverse environmental challenges. Several factors contribute to an animal's resilience including its ability to resist disease, cope with climatic extremes and respond to stressors. Immune competence, a proxy trait for general disease resistance, is expected to contribute to an animal's resilience. This research aimed to develop a practical method to assess immune competence in Merino sheep which would not restrict the future sale of tested animals, and to estimate genetic parameters associated with the novel trait. We also aimed to explore associations between immune competence and other industry-relevant disease resistance and fitness-related traits and to assess the ability of immune competence phenotypes to predict health outcomes. Here, the ability of Merino wethers (nâ¯=â¯1â¯339) to mount both an antibody-mediated and cell-mediated immune response was used to define their immune competence phenotype. For that purpose, antigens in a commercial vaccine were administered at the commencement of weaning and their responses were assessed. Univariate sire models were used to estimate variance components and heritabilities for immune competence and its component traits. Bivariate sire models were used to estimate genetic correlations between immune competence and a range of disease resistance and fitness-related traits. The heritability of immune competence and its component traits, antibody-mediated immune response and cell-mediated immune response were estimated at 0.49⯱â¯0.14, 0.52⯱â¯0.14 and 0.36⯱â¯0.11, respectively. Immune competence was favourably genetically correlated with breech flystrike incidence (-0.44⯱â¯0.39), worm egg count (-0.19⯱â¯0.23), dag score (-0.26⯱â¯0.31) and fitness compromise (-0.35⯱â¯0.24) but not fleece rot (0.17⯱â¯0.23). Results suggest that selection for immune competence has the potential to improve the resilience of Merino sheep; however, due to the large standard errors associated with correlation estimates reported here, further studies will be required in larger populations to validate associations between immune competence and disease resistance and fitness traits in Australian Merino sheep.
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Resistência à Doença , Animais , Austrália , Fenótipo , DesmameRESUMO
Venetian quarantine 400 years ago was an important public health measure. Since 1900 this has been refined to include "challenge" or deliberate infection with pathogens be they viruses, bacteria, or parasites. Our focus is virology and ranges from the early experiments in Cuba with Yellow Fever Virus to the most widespread pathogen of our current times, COVID-19. The latter has so far caused over four million deaths worldwide and 190 million cases of the disease. Quarantine and challenge were also used to investigate the Spanish Influenza of 1918 which caused over 100 million deaths. We consider here the merits of the approach, that is the speeding up of knowledge in a practical sense leading to the more rapid licensing of vaccines and antimicrobials. At the core of quarantine and challenge initiatives is the design of the unit to allow safe confinement of the pathogen and protection of the staff. Most important though is the safety of volunteers. We can see now, as in 1900, that members of our society are prepared and willing to engage in these experiments for the public good. Our ethnology study, where the investigator observed the experiment from within the quarantine, gave us the first indication of changing attitudes amongst volunteers whilst in quarantine. These quarantine experiments, referred to as challenge studies, human infection studies, or "controlled human infection models" involve thousands of clinical samples taken over two to three weeks and can provide a wealth of immunological and molecular data on the infection itself and could allow the discovery of new targets for vaccines and therapeutics. The Yellow Fever studies from 121 years ago gave the impetus for development of a successful vaccine still used today whilst also uncovering the nature of the Yellow Fever agent, namely that it was a virus. We outline how carefully these experiments are approached and the necessity to have high quality units with self-contained air-flow along with extensive personal protective equipment for nursing and medical staff. Most important is the employment of highly trained scientific, medical and nursing staff. We face a future of emerging pathogens driven by the increasing global population, deforestation, climate change, antibiotic resistance and increased global travel. These emerging pathogens may be pathogens we currently are not aware of or have not caused outbreaks historically but could also be mutated forms of known pathogens including viruses such as influenza (H7N9, H5N1 etc.) and coronaviruses. This calls for challenge studies to be part of future pandemic preparedness as an additional tool to assist with the rapid development of broad-spectrum antimicrobials, immunomodulators and new vaccines.
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Purpose: The aim was to assess the cost-effectiveness of robotic arm-assisted total hip arthroplasty (rTHA) compared with manual total hip arthroplasty (mTHA) and to assess the influence of annual volume on the relative cost-effectiveness of rTHA. Methods: A database of both rTHA (n = 48 performed in a private centre) and mTHA (n = 512 performed in the National Health Service) was used. Patient demographics, preoperative Oxford hip score, forgotten joint score, EuroQol 5-dimensional 3-level (EQ-5D), and postoperative EQ-5D were recorded. Two models for incremental cost-effectiveness ratios using cost per quality-adjusted life year (QALY) for rTHA were calculated based on a unit performing 100 rTHAs per year: 10-year follow-up and a lifetime time horizon (remaining life expectancy of a 69-year-old patient). Results: When adjusting for confounding factors, rTHA was independently associated with a 0.091 (p=0.029) greater improvement in the EQ-5D compared to mTHA. This resulted in a 10-year time horizon cost per QALY for rTHA of £1,910 relative to mTHA, which increased to £2,349 per QALY when discounted (5%/year). When using the 10-year time horizon cost per QALY was approximately £3,000 for a centre undertaking 50 rTHAs per year and decreased to £1,000 for centre undertaking 200 rTHAs per year. Using a lifetime horizon, the incremental unadjusted cost per QALY gained was £980 and £1432 when discounted (5%/year) for rTHA compared with mTHA. Conclusions: Despite the increased cost associated with rTHA, it was a cost-effective intervention relative to mTHA due to the associated greater health-related quality of health gain, according to the EQ-5D outcome measure.
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Pig production faces seasonal fluctuations. The low farrowing rate of sows mated in summer, increased carcass fatness of progeny born to the sows mated in summer, and slower growth rate of finisher pigs in summer are three economically important impacts identified in the pig industry. The purpose of this review is to examine advances over the past decade in understanding the mechanisms underlying the three impacts associated with summer conditions, particularly heat stress (HS), and to provide possible amelioration strategies. For impact 1, summer mating results in low farrowing rates mainly caused by the high frequency of early pregnancy disruptions. The contributions of semen DNA damage, poor oocyte quality, local progesterone concentrations, and suboptimal embryonic oestrogen secretion are discussed, as these all may contribute to HS-mediated effects around conception. Despite this, it is still unclear what the underlying mechanisms might be and thus, there is currently a lack of commercially viable solutions. For impact 2, there have been recent advances in the understanding of gestational HS on both the sow and foetus, with gestational HS implicated in decreased foetal muscle fibre number, a greater proportion of lighter piglets, and increased carcass fatness at slaughter. So far, no effective strategies have been developed to mitigate the impacts associated with gestational HS on foetuses. For impact 3, the slowed growth rate of pigs during summer is one reason for the reduced carcass weights in summer. Studies have shown that the reduction in growth rates may be due to more than reductions in feed intake alone, and the impaired intestinal barrier function and inflammatory response may also play a role. In addition, it is consistently reported that HS attenuates fat mobilisation which can potentially exacerbate carcass fatness when carcass weight is increased. Novel feed additives have exhibited the potential to reduce the impacts of HS on intestinal barrier function in grower pigs. Collectively, based on these three impacts, the economic loss associated with HS can be estimated. A review of these impacts is warranted to better align the future research directions with the needs of the pig industry. Ultimately, a better understanding of the underlying mechanisms and continuous investments in developing commercially viable strategies to combat HS will benefit the pig industry.
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Transtornos de Estresse por Calor , Doenças dos Suínos , Animais , Ingestão de Alimentos , Feminino , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico , Parto , Gravidez , Reprodução , SuínosRESUMO
Using an electronic medical record (EMR)-based dashboard, this study explored osteoporosis care gaps in primary care. Eighty-four physicians shared their practice activities related to bone mineral density testing, 10-year fracture risk calculation and treatment for those at high risk. Significant gaps in fracture risk calculation and osteoporosis management were identified. PURPOSE: To identify care gaps in osteoporosis management focusing on Canadian clinical practice guidelines (CPG) related to bone mineral density (BMD) testing, 10-year fracture risk calculation and treatment for those at high risk. METHODS: The ADVANTAGE OP EMR tool consists of an interactive algorithm to facilitate assessment and management of fracture risk using CPG. The FRAX® and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools were embedded to facilitate 10-year fracture risk calculation. Physicians managed patients as clinically indicated but with EMR reminders of guideline recommendations; participants shared practice level data on management activities after 18-month use of the tool. RESULTS: Eighty-four physicians (54%) of 154 who agreed to participate in this study shared their aggregate practice activities. Across all practices, there were 171,310 adult patients, 40 years of age and older, of whom 17,214 (10%) were at elevated risk for fracture. Sixty-two percent of patients potentially at elevated risk for fractures did not have BMD testing completed; most common reasons for this were intention to order BMD later (48%), physician belief that BMD was not required (15%) and patient refusal (20%). For patients with BMD completed, fracture risk was calculated in 29%; 19% were at high risk, of whom 37% were not treated with osteoporosis medications as recommended by CPG. CONCLUSION: Despite access to CPG and fracture risk calculators through the ADVANTAGE OP EMR tool, significant gaps remain in fracture risk calculation and osteoporosis management. Additional strategies are needed to address this clinical inertia among family physicians.
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Osteoporose , Fraturas por Osteoporose , Adulto , Densidade Óssea , Canadá , Registros Eletrônicos de Saúde , Humanos , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Medição de Risco , Fatores de RiscoRESUMO
To date, projections of human migration induced by sea-level change (SLC) largely suggest large-scale displacement away from vulnerable coastlines. However, results from our model of Bangladesh suggest counterintuitively that people will continue to migrate toward the vulnerable coastline irrespective of the flooding amplified by future SLC under all emissions scenarios until the end of this century. We developed an empirically calibrated agent-based model of household migration decision-making that captures the multi-faceted push, pull and mooring influences on migration at a household scale. We then exposed ~4800 000 simulated migrants to 871 scenarios of projected 21st-century coastal flooding under future emissions pathways. Our model does not predict flooding impacts great enough to drive populations away from coastlines in any of the scenarios. One reason is that while flooding does accelerate a transition from agricultural to non-agricultural income opportunities, livelihood alternatives are most abundant in coastal cities. At the same time, some coastal populations are unable to migrate, as flood losses accumulate and reduce the set of livelihood alternatives (so-called 'trapped' populations). However, even when we increased access to credit, a commonly-proposed policy lever for incentivizing migration in the face of climate risk, we found that the number of immobile agents actually rose. These findings imply that instead of a straightforward relationship between displacement and migration, projections need to consider the multiple constraints on, and preferences for, mobility. Our model demonstrates that decision-makers seeking to affect migration outcomes around SLC would do well to consider individual-level adaptive behaviors and motivations that evolve through time, as well as the potential for unintended behavioral responses.
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The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.
Le programme de lignes directrices de la Société canadienne de cardiologie (SCC) en matière de fibrillation auriculaire (FA) a été élaboré pour aider les cliniciens à prendre en charge ces patients complexes, ainsi que pour orienter les décideurs politiques et les systèmes de soins de santé sur des questions connexes. La dernière édition complète des lignes directrices de la SCC en matière de FA a été publiée en 2010. Depuis lors, des mises à jour périodiques ont été publiées, traitant de domaines en évolution rapide. Cependant, en 2020, un grand nombre de développements s'y étaient ajoutés, couvrant un large éventail de domaines, ce qui a motivé le comité à créer une refonte complète des lignes directrices. L'édition 2020 des lignes directrices de la SCC en matière de FA représente un renouvellement complet qui intègre, met à jour et remplace les lignes directrices, les recommandations et les conseils pratiques des dix dernières années. Elle est destinée à être utilisée par les cliniciens praticiens de toutes les disciplines qui s'occupent de patients souffrant de FA. L'approche GRADE (Gradation des Recommandations, de l'Appréciation, du Développement et des Évaluations) a été utilisée pour évaluer la pertinence des recommandations et la qualité des résultats. Les domaines d'intérêt incluent : la classification et les définitions de la FA, son épidémiologie, sa physiopathologie, l'évaluation clinique, le dépistage de la FA, la détection et la gestion des facteurs de risque modifiables, l'approche intégrée de la gestion de la FA, la prévention des accidents vasculaires cérébraux, la gestion de l'arythmie, les différences entre les sexes et la FA dans des populations particulières. Des tableaux et figures ont été largement utilisés pour synthétiser les éléments importants et présenter les concepts clés. Ce document devrait représenter une aide importante pour l'intégration des connaissances et un outil pour aider à améliorer la gestion clinique de cette arythmie importante et difficile à traiter.
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Humanos , Masculino , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Fibrilação Atrial/classificação , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/epidemiologia , Grupos de Risco , Algoritmos , Fatores Sexuais , Fatores de Risco , Procedimentos Clínicos , Acidente Vascular Cerebral/prevenção & controleRESUMO
The ^{80}Ge structure was investigated in a high-statistics ß-decay experiment of ^{80}Ga using the GRIFFIN spectrometer at TRIUMF-ISAC through γ, ß-e, e-γ, and γ-γ spectroscopy. No evidence was found for the recently reported 0_{2}^{+} 639-keV level suggested as evidence for low-energy shape coexistence in ^{80}Ge. Large-scale shell model calculations performed in ^{78,80,82}Ge place the 0_{2}^{+} level in ^{80}Ge at 2 MeV. The new experimental evidence combined with shell model predictions indicate that low-energy shape coexistence is not present in ^{80}Ge.
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Virtually all climate monitoring and forecasting efforts concentrate on hazards rather than on impacts, while the latter are a priority for planning emergency activities and for the evaluation of mitigation strategies. Effective disaster risk management strategies need to consider the prevailing "human terrain" to predict who is at risk and how communities will be affected. There has been little effort to align the spatiotemporal granularity of socioeconomic assessments with the granularity of weather or climate monitoring. The lack of a high-resolution socioeconomic baseline leaves methodical approaches like machine learning virtually untapped for pattern recognition of extreme climate impacts on livelihood conditions. While the request for "better" socioeconomic data is not new, we highlight the need to collect and analyze environmental and socioeconomic data together and discuss novel strategies for coordinated data collection via mobile technologies from a drought risk management perspective. A better temporal, spatial, and contextual understanding of socioeconomic impacts of extreme climate conditions will help to establish complex causal pathways and quantitative proof about climate-attributable livelihood impacts. Such considerations are particularly important in the context of the latest big data-driven initiatives, such as the World Bank's Famine Action Mechanism (FAM).
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AIM: To report the outcome of 150 patients using the Hologic LOCalizer RFID (radiofrequency identification) tag system, including the first reported use of RFID tags in the axilla. MATERIALS AND METHODS: Data were collected prospectively from the first tag insertion (12 June 2019) until 150 consecutive patients had undergone surgery (excision date 9 January 2020). RESULTS: A total of 177 tags were targeted to 177 malignant lesions in 150 women. Tags were inserted an average of 7.8 days before surgery (range 0-71 days). One hundred and twenty-six tags were targeted to a single lesion in one breast only; the remainder of tags were targeted to multiple lesions in one or both breasts, as well as to axillary lymph nodes. In addition, two cases involved the use of two tags to bracket microcalcification. All except three tags were satisfactorily deployed at their initial intended target. The majority of target lesions were masses (n=142, mean size 13.8 mm), with a range of other targets including post-vacuum-assisted biopsy cavities, marker clips post-neoadjuvant chemotherapy, architectural distortions, and clipped metastatic lymph nodes. All tags were successfully retrieved at surgical excision. Re-excision rate was 8.7%. There were no tag-specific surgical complications. CONCLUSIONS: The RFID tag system demonstrates many advantages over guidewires, and is effective at targeting axillary lymph nodes and multiple sites within the same breast.
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Neoplasias da Mama/patologia , Metástase Linfática/patologia , Dispositivo de Identificação por Radiofrequência , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estudos Prospectivos , Técnicas Estereotáxicas , Ultrassonografia de Intervenção , Reino UnidoRESUMO
The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.
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Insuficiência Cardíaca , Coração Auxiliar , Adulto , Estudos de Viabilidade , Terapia Genética , Vetores Genéticos/genética , Insuficiência Cardíaca/terapia , Humanos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
AIMS: The primary aim of the study was to compare the knee-specific functional outcome of robotic unicompartmental knee arthroplasty (rUKA) with manual total knee arthroplasty (mTKA) for the management of isolated medial compartment osteoarthritis. Secondary aims were to compare length of hospital stay, general health improvement, and satisfaction between rUKA and mTKA. METHODS: A powered (1:3 ratio) cohort study was performed. A total of 30 patients undergoing rUKA were propensity score matched to 90 patients undergoing mTKA for isolated medial compartment arthritis. Patients were matched for age, sex, body mass index (BMI), and preoperative function. The Oxford Knee Score (OKS) and EuroQol five-dimension questionnaire (EQ-5D) were collected preoperatively and six months postoperatively. The Forgotten Joint Score (FJS) and patient satisfaction were collected six months postoperatively. Length of hospital stay was also recorded. RESULTS: There were no significant differences in the preoperative demographics (p ⩾ 0.150) or function (p ⩾ 0.230) between the groups. The six-month OKS was significantly greater in the rUKA group when compared with the mTKA group (difference 7.7, p < 0.001). There was also a greater six-month postoperative EQ-5D (difference 0.148, p = 0.002) and FJS (difference 24.2, p < 0.001) for the rUKA when compared to the mTKA. No patient was dissatisfied in the rUKA group and five (6%) were dissatisfied in the mTKA, but this was not significant (p = 0.210). Length of stay was significantly (p < 0.001) shorter in the rUKA group (median two days, interquartile range (IQR) 1 to 3) compared to the mTKA (median four days, IQR 3 to 5). CONCLUSION: Patients with isolated medial compartment arthritis had a greater knee-specific functional outcome and generic health with a shorter length of hospital stay after rUKA when compared to mTKA.Cite this article: Bone Joint Res 2019;9(1):15-22.
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OBJECTIVES: We described the epidemiology and healthcare exposures during a measles outbreak in London and identified factors associated with isolation on arrival to healthcare premises. STUDY DESIGN: We conducted a cohort study including all confirmed measles cases in London residents from February 1, 2016, to June 30, 2016, and semistructured interviews with two infection prevention and control teams (IPCTs). METHODS: We described the outbreak and conducted a multilevel mixed-effects analysis to assess the relationship between sociodemographic and clinical factors and isolation on arrival to healthcare premises. We summarised the interviews. RESULTS: There were 182 cases, mostly aged 17-35 years (46%; 84). Excluding cases younger than one year, 76% (92/120) were unvaccinated, including two healthcare workers. The majority presented with rash (97%; 174), and 42% (70/166) required hospitalisation. Of the recorded cases, 93% of cases (164/178) had visited a healthcare setting during their infectious period (median number of visits = 2). In 33% (59/178) of the visits, the case was isolated on arrival; when not isolated, four healthcare exposures resulted in further transmission. Presenting to the hospital as opposed to a general practitioner (GP) was associated with higher odds of isolation (odds ratio = 2.23, 95% confidence interval = 1.1-4.4) when adjusted for age, gender and presenting with a cough. The IPCT identified measles training using standardised risk assessments by triage nurses in accident and emergency and intelligence regarding measles activity in the community as positive measures to prevent healthcare exposures. CONCLUSIONS: We recommend opportunistic immunisation of unvaccinated young adults by GPs and that occupational health departments ensure their staff are protected against measles. Raising measles awareness in healthcare settings via training or regular sharing of current measles surveillance activity from public health to the IPCT and GP may improve triage and isolation of cases on arrival to healthcare premises.