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OBJECTIVE: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using immunohistochemical (IHC) analysis are mixed regarding whether and which tumor infiltrating lymphocytes (TILs) impact survival, and IHC does not adequately quantify rare cell populations, including CD137+ (4-1BB) tumor-reactive TILs. Our study investigates if a higher percentage of CD3+ CD137+ TILs is associated with improved overall survival (OS) in OC. METHODS: Flow cytometry was performed on viably banked OC digests. Chart review and statistical analysis were performed. Forty-seven patients were included, 40 of whom were diagnosed with high-grade serous ovarian carcinoma (HGSOC), papillary serous carcinoma, or undifferentiated histology. RESULTS: A high percentage of CD3+ CD137+ TILs correlated with improved OS (n = 40, r = 0.48, P = 0.0016). Subjects were divided into CD3+ CD137+ TIL high and low groups by the median. Subjects with high CD3+CD137+ TIL frequencies (>9.6%) had longer OS (Wilcoxon rank-sum test; P = 0.0032) and improved OS (logrank test; P = 0.007). Differences in CD3+ or CD3+ CD8+ TILs did not impact survival. CD3+ CD137+ TILs were predictive of OS regardless of germline mutation or debulking status. Analysis of subgroups including late stage HGSOC and late stage HGSOC with primary optimal cytoreduction indicated CD3+ CD137+ TILs correlated with improved OS after adjusting for age and PARP inhibitor use (P = 0.034 and P = 0.016, respectively). CONCLUSIONS: Prevalence of CD3+ CD137+ TILs in digested OC specimens is associated with improved OS, while general TIL markers are not. CD137 has the potential to be a novel biomarker for survival in OC.
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Linfócitos do Interstício Tumoral , Neoplasias Ovarianas , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Humanos , Feminino , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/análise , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Pessoa de Meia-Idade , Idoso , Complexo CD3/análise , Adulto , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/mortalidade , Idoso de 80 Anos ou maisRESUMO
The primary underlying contributor for cataract, a leading cause of vision impairment and blindness worldwide, is oxidative stress. Oxidative stress triggers protein damage, cell apoptosis, and subsequent cataract formation. The nuclear factor-erythroid 2-related factor 2 (Nrf2) serves as a principal redox transcriptional factor in the lens, offering a line of defense against oxidative stress. In response to oxidative challenges, Nrf2 dissociates from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1), moves to the nucleus, and binds to the antioxidant response element (ARE) to activate the Nrf2-dependent antioxidant system. In parallel, oxidative stress also induces endoplasmic reticulum stress (ERS). Reactive oxygen species (ROS), generated during oxidative stress, can directly damage proteins, causing them to misfold. Initially, the unfolded protein response (UPR) activates to mitigate excessive misfolded proteins. Yet, under persistent or severe stress, the failure to rectify protein misfolding leads to an accumulation of these aberrant proteins, pushing the UPR towards an apoptotic pathway, further contributing to cataractogenesis. Importantly, there is a dynamic interaction between the Nrf2 antioxidant system and the ERS/UPR mechanism in the lens. This interplay, where ERS/UPR can modulate Nrf2 expression and vice versa, holds potential therapeutic implications for cataract prevention and treatment. This review explores the intricate crosstalk between these systems, aiming to illuminate strategies for future advancements in cataract prevention and intervention. The Nrf2-dependent antioxidant system communicates and cross-talks with the ERS/UPR pathway. Both mechanisms are proposed to play pivotal roles in the onset of cataract formation.
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Antioxidantes , Catarata , Humanos , Antioxidantes/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Many non-invasive prenatal testing (NIPT) platforms screen for sex chromosome aneuploidy (SCA) and SCA analysis is generally included in Australia where NIPT is available as a self-funded test. Little is known about the experience of receiving an NIPT result indicating an increased chance of SCA. This study aimed to explore the experiences of people who received this result and their perspectives on the information, care, and support they received from healthcare practitioners (HCPs). Semi-structured interviews were conducted with people who received an NIPT result indicating an increased chance of SCA and continued their pregnancy. Most participants only had contact with a genetic counselor after receiving their result. Transcribed data were analyzed using rigorous thematic analysis to identify important patterns and themes. Participants (18 women, 2 male partners) described embarking on NIPT, primarily based on advice from their HCP and without much consideration. Consequently, participants expressed feeling unprepared for the unanticipated complexity of their NIPT result and were faced with making a time-sensitive decision about a condition they had not previously considered. While more pre-test information was desired, timely access to genetic counseling post-test assisted with adjustment to the result. These findings suggest that routinization of NIPT may be compromising informed decision-making, resulting in unpreparedness for an increased chance result. Given the increasing uptake and expanding scope of NIPT, resources should be dedicated to educating HCPs offering NIPT and ensuring timely access to genetic counseling post-result. With appropriate funding, genetics services may be able to play a central role in offering information and support to both people who undertake NIPT and their HCPs ordering the testing. Implementing a publicly funded screening program in Australia could assist with standardizing prenatal screening care pathways and consequently better access to appropriate resources.
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Aneuploidia , Testes Genéticos , Gravidez , Feminino , Masculino , Humanos , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Aberrações dos Cromossomos Sexuais , Austrália , Cromossomos SexuaisRESUMO
BACKGROUND: Acute atrial fibrillation is the most common arrythmia treated in the emergency department. Our primary aim was to compare conversion to sinus rhythm between pharmacological cardioversion followed by electrical cardioversion (drug-shock), and electrical cardioversion alone (shock-only). Our secondary aim was to compare the effectiveness of two pad positions for electrical cardioversion. METHODS: We did a partial factorial trial of two protocols for patients with acute atrial fibrillation at 11 academic hospital emergency departments in Canada. We enrolled adult patients with acute atrial fibrillation. Protocol 1 was a randomised, blinded, placebo-controlled comparison of attempted pharmacological cardioversion with intravenous procainamide (15 mg/kg over 30 min) followed by electrical cardioversion if necessary (up to three shocks, each of ≥200 J), and placebo infusion followed by electrical cardioversion. For patients having electrical cardioversion, we used Protocol 2, a randomised, open-label, nested comparison of anteroposterior versus anterolateral pad positions. Patients were randomly assigned (1:1, stratified by study site) for Protocol 1 by on-site research personnel using an online electronic data capture system. Randomisation for Protocol 2 occurred 30 min after drug infusion for patients who had not converted and was stratified by site and Protocol 1 allocation. Patients and all research and emergency department staff were masked to treatment allocation for Protocol 1. The primary outcome was conversion to normal sinus rhythm for at least 30 min at any time after randomisation and up to a point immediately after three shocks. Protocol 1 was analysed by intention to treat and Protocol 2 excluded patients who did not receive electrical cardioversion. This study is registered at ClinicalTrials.gov, number NCT01891058. FINDINGS: Between July 18, 2013, and Oct 17, 2018, we enrolled 396 patients, and none were lost to follow-up. In the drug-shock group (n=204), conversion to sinus rhythm occurred in 196 (96%) patients and in the shock-only group (n=192), conversion occurred in 176 (92%) patients (absolute difference 4%; 95% CI 0-9; p=0·07). The proportion of patients discharged home was 97% (n=198) versus 95% (n=183; p=0·60). 106 (52%) patients in the drug-shock group converted after drug infusion only. No patients had serious adverse events in follow-up. The different pad positions in Protocol 2 (n=244), had similar conversions to sinus rhythm (119 [94%] of 127 in anterolateral group vs 108 [92%] of 117 in anteroposterior group; p=0·68). INTERPRETATION: Both the drug-shock and shock-only strategies were highly effective, rapid, and safe in restoring sinus rhythm for patients in the emergency department with acute atrial fibrillation, avoiding the need for return to hospital. The drug infusion worked for about half of patients and avoided the resource intensive procedural sedation required for electrical cardioversion. We also found no significant difference between the anterolateral and anteroposterior pad positions for electrical cardioversion. Immediate rhythm control for patients in the emergency department with acute atrial fibrillation leads to excellent outcomes. FUNDING: Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research.
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Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Cardioversão Elétrica , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos Clínicos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
ABSTRACTObjective:Our aims were to report an analysis of the concept of cultural competency and to explore how the cultural competency of the palliative care workforce impacts the holistic care of young people with palliative care needs from South Asian cultures. METHOD: Using keywords, we searched the online databases MEDLINE, CINAHL, ScienceDirect, and PubMed from January of 1990 through to December of 2016. Some 1543 articles were retrieved, and inclusion and exclusion criteria were applied. A total of 38 papers were included in the concept analysis. The data were analyzed using Coad's (2002) adapted framework based on Rodgers's (1989) evolutionary concept analysis, focusing on the attributes, antecedents, consequences, and related terms in relation to culturally competent care. A model case of culturally competent care was also constructed. RESULTS: The literature provides evidence that the concept of culturally competent care is a complex one, which is often expressed ambiguously. In addition, there is a paucity of research that involves service users as experts in defining their own needs and assessing their experiences related to cultural care. SIGNIFICANCE OF RESULTS: Cultural care should be integral to holistic patient care, irrespective of a person's race or ethnicity. There is an urgent need to involve young BAME patients with palliative care needs and their families in the development of a robust tool to assess cultural competency in clinical practice.
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Povo Asiático/psicologia , Competência Cultural/psicologia , Cuidados Paliativos/normas , Satisfação do Paciente , Ásia/etnologia , Povo Asiático/etnologia , Formação de Conceito , Humanos , Cuidados Paliativos/métodosRESUMO
It is estimated that rare diseases affect the lives of over three million people in the United Kingdom. Of these, a significant proportion are children and young people with genetic life-limiting or life-shortening conditions. This study used a qualitative approach with in-depth semi-structured interviews to explore the experiences of 10 adult siblings of a baby diagnosed with Trisomy 13 (Patau syndrome) or Trisomy 18 (Edward syndrome). Findings illustrate that parental grief from the time of their child's diagnosis onward is also experienced by siblings. Although young adults may have conflicting feelings as a bereaved sibling, there is evidence that the experience impacts on their world views and their attitudes about prospective and expectant parenthood. The study highlights the importance of providing siblings with short-term and long-term support from the time of their brother's or their sister's diagnosis onward and provides new understanding about benefit of professional and peer support in helping young adults develop resilience and coping strategies.
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This article presents an original study commissioned by the UK charity, Together for Short Lives which explored children and young people up to 25 years of age with life-threatening/limiting conditions and their families. Using Appreciative Inquiry and framework analysis, qualitative work sought to explore perceived met and unmet needs of services and care. Fifty-one families were interviewed from one UK area, 18 of which were children/young people up to 25 years old. Findings indicated that children and their families felt medical/nursing needs were well met but provision was needed for broader financial, social and emotional support alongside more responsive specialist therapies.
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Estado Terminal/mortalidade , Atenção à Saúde/estatística & dados numéricos , Expectativa de Vida , Avaliação das Necessidades , Cuidados Paliativos/métodos , Adolescente , Adulto , Fatores Etários , Criança , Doença Crônica , Estado Terminal/terapia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Percepção , Doenças Raras , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Reino UnidoRESUMO
INTRODUCTION: Intravesical sequential doublet chemotherapy (SDC) is being used increasingly as a rescue treatment for nonmuscle-invasive bladder cancer failing bacillus Calmette-Guérin (BCG), as single-agent chemotherapies are less effective, especially for carcinoma in situ. Considering the current BCG shortage, intravesical SDC also provides an efficacious alternative to BCG. Our aim is to detail the implementation to assist with establishing an efficient and practical intravesical SDC clinic for urologic practice. METHODS: We searched PubMed for published studies with the Medical Subject Heading of "intravesical chemotherapy" and "non-muscle invasive bladder cancer." The search was limited to English-language journals and full papers only. The initial search resulted in 260 articles, of which 20 relevant studies were selected. RESULTS: Five important processes were identified in the successful and efficient administration of intravesical SDC: (1) patient preparation, (2) medication procurement, (3) medication administration, (4) medication immediate aftermath, and (5) patient instruction and education. Safety precautions should be taken when handling each chemotherapy drug. A clinical pharmacist may be required for drug preparation. An important step in providing intravesical SDC is to use a closed system for the instillation of the chemo-solution. A special protocol should be adopted for every drug with its proper dwell time. The induction course consists of weekly instillation for 6 weeks. If an initial response is noted, maintenance therapy is recommended, typically monthly for 24 months. CONCLUSIONS: Successful intravesical SDC clinics necessitate appropriate patient selection, standardized workflow procedures, patient education, and good communication between the urologist, clinical pharmacists, and oncology nurses.
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Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Administração Intravesical , Invasividade Neoplásica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Instituições de Assistência Ambulatorial/organização & administraçãoRESUMO
BACKGROUND: We sought to improve the immediate and subsequent care of emergency department (ED) patients with acute atrial fibrillation (AF) and flutter (AFL) by implementing the principles of the Canadian Association of Emergency Physicians AF/AFL Best Practices Checklist. METHODS: This cohort study included 3 periods: before (7 months), intervention introduction (1 month), and after (7 months), and was conducted at a major academic centre. We included patients who presented with an episode of acute AF or AFL and used multiple strategies to support ED adoption of the Canadian Association of Emergency Physicians checklist. We developed new cardiology rapid-access follow-up processes. The main outcomes were unsafe and suboptimal treatments in the ED. RESULTS: We included 1108 patient visits, with 559 in the before and 549 in the after period. In a comparison of the periods, there was an increase in use of chemical cardioversion (20.6% vs 25.0%; absolute difference [AD], 4.4%) and in electrical cardioversion (39.2% vs 51.2%; AD, 12.0%). More patients were discharged with sinus rhythm restored (66.9% vs 75.0%; AD, 8.1%). The proportion seen in a follow-up cardiology clinic increased from 24.2% to 39.9% (AD, 15.7%) and the mean time until seen decreased substantially (103.3 vs 49.0 days; AD, -54.3 days). There were very few unsafe cases (0.4% vs 0.7%) and, although there was an increase in suboptimal care (19.5% vs 23.1%), overall patient outcomes were excellent. CONCLUSIONS: We successfully improved the care for ED patients with acute AF/AFL and achieved more frequent and more rapid cardiology follow-up. Although cases of unsafe management were uncommon and patient outcomes were excellent, there are opportunities for physicians to improve their care of acute AF/AFL patients. GOV IDENTIFIER: NCT05468281.
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Background: Acute heart failure (AHF) is a common emergency department (ED) presentation that may have poor outcomes but often does not require hospital admission. There is little evidence to guide dispositional decisions. Objectives: The authors sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF. Methods: We pooled data from 3 prospective cohorts: 2 published studies and 1 new cohort. The 3 cohorts prospectively enrolled patients who required treatment for AHF at 10 tertiary care hospital EDs. The primary outcome was SSO, defined as death <30 days, intubation or noninvasive ventilation (NIV), myocardial infarction, or relapse to ED <14 days. The logistic regression model evaluated 13 predictors, used an AIC-based step-down procedure, and bootstrapped internal validation. Results: Of the 2,246 patients in the 3 cohorts (N = 559; 1,100; 587), the mean age was 77.4 years, 54.5% were male, 3.1% received intravenous nitroglycerin, 5.2% received ED NIV, and 48.6% were admitted to the hospital. There were 281 (12.5%) SSOs including 70 deaths (3.1%) with many in discharged patients. The final HEARTRISK6 Scale included 6 variables: valvular heart disease, tachycardia, need for NIV, creatinine, troponin, and failed reassessment (walk test). Choosing HEARTRISK6 total-point admission thresholds of ≥1 or ≥2 would yield, respectively, sensitivities of 88.3% (95% CI: 83.9%-91.8%) and 71.5% (95% CI: 65.9%-76.7%) and specificities of 24.7% (95% CI: 22.8%-26.7%) and 50.1% (95% CI: 47.9%-52.4%) for SSO. Conclusions: Using 3 large prospectively collected datasets, we created a concise and sensitive risk scale for patients with AHF in the ED. Implementation of the HEARTRISK6 scale could lead to safer and more efficient disposition decisions.
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INTRODUCTION: Acute heart failure patients often have an uncertain or delayed follow-up after discharge from the ED. Our goal was to introduce rapid-access specialty clinics to ensure acute heart failure patients were seen within 7 days, in an effort to reduce admissions and improve follow-up care. METHODS: This prospective cohort study was conducted at two campuses of a large tertiary care hospital. We enrolled acute heart failure patients who presented to the ED with shortness of breath and were later discharged. Following a 12-month before period, we introduced rapid-access acute heart failure clinics staffed by cardiology and internal medicine. We allowed for a 3-month implementation period and then observed outcomes over the subsequent 12-month after period. The primary outcome was hospital admission within 30 days. Secondary outcomes included mortality and actual access to specialty care. RESULTS: Patients in the before (N = 355) and after periods (N = 374) were similar for age and most characteristics. Segmented autoregression analysis demonstrated there was a pre-existing trend to fewer admissions. Attendance at a specialty clinic increased from 17.8 to 42.1% (P < 0.01) and the median days to the clinic decreased from 13 to 6 days (P < 0.01). 30-days mortality did not change. CONCLUSION: Implementation of rapid-access clinics for acute heart failure patients discharged from the ED did not lead to an overall decrease in hospital admissions. It did, however, lead to increased access to specialist care, reduced follow-up times, without an increase in return ED visits or mortality. Widespread use of this rapid-access approach to a specialist can improve care for acute heart failure patients discharged home from the ED.
RéSUMé: INTRODUCTION: Les patients atteints d'insuffisance cardiaque aiguë ont souvent un suivi incertain ou retardé après leur sortie de l'urgence. Notre objectif était de mettre en place des cliniques spécialisées à accès rapide pour veiller à ce que les patients de d'insuffisance cardiaque aiguë soient vus dans les sept jours, afin de réduire les admissions et d'améliorer les soins de suivi. MéTHODES: Cette étude de cohorte prospective a été menée sur deux campus d'un grand hôpital de soins tertiaires. Nous avons recruté des patients atteints de d'insuffisance cardiaque aiguë qui se sont présentés aux urgences avec un essoufflement et qui ont ensuite été renvoyés chez eux. Après une période antérieure de 12 mois, nous avons mis en place des cliniques de d'insuffisance cardiaque aiguë à accès rapide dotées de personnel en cardiologie et en médecine interne. Nous avons prévu une période de mise en Åuvre de 3 mois et avons ensuite observé les résultats au cours des 12 mois suivants. Le résultat principal était l'admission à l'hôpital dans les 30 jours. Les résultats secondaires comprenaient la mortalité et l'accès réel aux soins spécialisés. RéSULTATS: Les patients des périodes avant (N = 355) et après (N = 374) étaient similaires pour l'âge et la plupart des caractéristiques. Une analyse d'autorégression segmentée a démontré qu'il y avait une tendance préexistante à moins d'admissions. La fréquentation d'une clinique spécialisée est passée de 17,8 % à 42,1 % (P < 0,01) et les jours médians à la clinique ont diminué de 13 à 6 jours (P < 0,01). La mortalité à 30 jours n'a pas changé. CONCLUSION: La mise en place de cliniques à accès rapide pour les patients d'insuffisance cardiaque aiguë sortant de l'urgence n'a pas entraîné une diminution globale des admissions à l'hôpital Elle a toutefois permis d'améliorer l'accès aux soins spécialisés et de réduire les délais de suivi, sans pour autant augmenter les visites de retour aux urgences ou la mortalité. L'utilisation généralisée de cette approche d'accès rapide à un spécialiste peut améliorer les soins pour les patients atteints de d'insuffisance cardiaque aiguë renvoyés chez eux par les services d'urgence.
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Serviço Hospitalar de Emergência , Insuficiência Cardíaca , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hospitalização , Humanos , Alta do Paciente , Estudos ProspectivosRESUMO
BACKGROUND: Acute atrial flutter has one-tenth the prevalence of acute atrial fibrillation in the emergency department (ED) but shares many management strategies. Our aim was to compare conversion from acute atrial flutter to sinus rhythm between pharmacological cardioversion followed by electrical cardioversion (Drug-Shock), and electrical cardioversion alone (Shock-Only). METHODS: We conducted a randomized, blinded, placebo-controlled comparison of attempted pharmacological cardioversion with IV procainamide followed by electrical cardioversion if necessary, and placebo infusion followed by electrical cardioversion. We enrolled stable patients with a primary diagnosis of acute acute atrial flutter at 11 academic EDs. The primary outcome was conversion to normal sinus rhythm. FINDINGS: From July 2013 to October 2018, we enrolled 76 patients, and none were lost to follow-up. Comparing the Drug-Shock to the Shock-Only group, conversion to sinus rhythm occurred in 33 (100%) versus 40 (93%) (absolute difference 7.0%; 95% CI - 0.6 to 14.6; P = 0.25). Median time to conversion from start of infusion in the Drug-Shock group was 24 min (IQR 21-82) but only 9 (27%) cases were converted with IV procainamide. Patients in both groups had similar outcomes at 14 days; there were no strokes or deaths. INTERPRETATION: This trial found that the Drug-Shock strategy is potentially superior but that either approach to immediate rhythm control in the ED for patients with acute acute atrial flutter is highly effective, rapid, and safe in restoring sinus rhythm and allowing patients to go home and return to normal activities. Unlike the case of atrial fibrillation, we found that IV procainamide alone was infrequently effective.
RéSUMé: CONTEXTE: Le flutter auriculaire aigu a un dixième de la prévalence de la fibrillation auriculaire aiguë aux services d'urgence (SU) mais partage de nombreuses stratégies de gestion. Notre objectif était de comparer la conversion du flutter auriculaire aigu en rythme sinusal entre la cardioversion pharmacologique suivie de la cardioversion électrique (Drug-Shock) et la cardioversion électrique seule (Shock-Only). MéTHODES: Nous avons effectué une comparaison randomisée, en aveugle et contrôlée par placebo d'une tentative de cardioversion pharmacologique avec le procaïnamide IV suivie d'une cardioversion électrique si nécessaire, et une perfusion de placebo suivie d'une cardioversion électrique. Nous avons inscrit des patients stables avec un diagnostic primaire de flutter auriculaire aigu aigu dans 11 services d'urgence universitaires. Le résultat principal était la conversion à un rythme sinusal normal. RéSULTATS: De juillet 2013 à octobre 2018, nous avons inscrit 76 patients qui ont tous poursuivi le suivi médical jusqu'au terme prévu. En comparant le groupe Drug-Shock au groupe Shock-Only, la conversion au rythme sinusal s'est produite dans 33 (100%) contre 40 (93%) (différence absolue 7,0%; IC à 95% − 0.6 à 14,6; P = 0,25). Le temps médian de conversion depuis le début de la perfusion dans le groupe Drug-Shock était de 24 min (IQR 2182) mais seulement 9 (27%) cas ont converti avec le procaïnamide IV. Les patients des deux groupes ont eu des résultats similaires à 14 jours; il n'y a pas eu d'accident vasculaire cérébral ni de décès. INTERPRéTATION: Cet essai a révélé que la stratégie Drug-Shock s'est avérée potentiellement supérieure, mais quelle que soit l'approche du contrôle immédiat du rythme cardiaque aux urgences pour les patients atteints de flutter auriculaire aigu aigu, elles sont, tous les deux, très efficaces, rapides et sûres pour rétablir le rythme sinusal et permettre aux patients de rentrer chez eux et reprendre leurs activités normales. Contrairement au cas de la fibrillation auriculaire, nous avons constaté que le procaïnamide IV seul était rarement efficace.
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Fibrilação Atrial , Flutter Atrial , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Flutter Atrial/tratamento farmacológico , Cardioversão Elétrica , Serviço Hospitalar de Emergência , Humanos , ProcainamidaRESUMO
BACKGROUND: We sought to evaluate safety of electrical cardioversion (ECV) for patients with acute atrial fibrillation (AF) or atrial flutter (AFL) in the emergency department (ED). METHODS: This was an analysis of data from 4 multicentre AF/AFL studies conducted from 2008 to 2019 at 23 large EDs. We included adult patients who received attempts at ECV and who had presented acutely after symptom onset. Staff manually reviewed study and clinical records to abstract data. RESULTS: We evaluated 1736 ECV cases with a mean age of 60.1 years and 67.1% male. The overall success of ECV was 90.2% (95% confidence interval 88.7%-91.6%), with 4.9% of patients admitted. ED physicians performed the ECV in 95.2% and provided sedation in 96.5%; 13.9% (12.3%-15.7%) of cases experienced important adverse events that required treatment, and 0.4% were classified as life threatening. Another 5.6% had adverse events that did not require treatment. Logistic regression found that the RAFF-3 study cohort (odds ratio [OR] 2.0), age ≥ 85 years (OR 2.1), coronary artery disease (OR 1.5), midazolam (OR 1.9), and fentanyl (OR 1.5) were associated with important adverse events. CONCLUSIONS: This large evaluation of the safety of ECV for acute AF/AFL in the ED found that while serious adverse events were rare, there were a concerning number of events following sedation that required intervention. Physicians should be aware that older age, coronary artery disease, and fentanyl are associated with higher risks of important adverse events. This study provides more information for shared decision making discussions with patients when choosing between drug-shock and shock-only cardioversion strategies.
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Fibrilação Atrial/terapia , Flutter Atrial/terapia , Tomada de Decisão Compartilhada , Cardioversão Elétrica/efeitos adversos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Greenberg dysplasia is a rare, autosomal recessive, prenatal lethal bone dysplasia caused by biallelic pathogenic variants in the lamin B receptor (LBR) gene. Pathogenic variants in LBR are also associated with Pelger-Huët anomaly, an autosomal dominant benign abnormality of the nuclear shape and chromatin organization of blood granulocytes, and Pelger-Huët anomaly with variable skeletal anomalies, a mild, regressing to moderate-severe autosomal recessive condition. Conditions with abnormal sterol metabolism and different genetic basis have clinical and radiographic features similar to Greenberg dysplasia, for example X-linked dominant chondrodysplasia punctata, Conradi-Hünermann type, and CHILD syndrome, and other conditions with unknown genetic etiology display very similar features, for example, dappled diaphyseal dysplasia and Astley-Kendall dysplasia. METHODS: We present a fetus with typical clinical and radiographic features of Greenberg dysplasia, and review the literature. RESULTS: Genetic testing confirmed the diagnosis Greenberg dysplasia: homozygosity for a pathogenic variant in LBR. CONCLUSION: Comparing the clinical and radiographic phenotypes of Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley-Kendall dysplasia, we suggest that these are allelic disorders.
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Condrodisplasia Punctata/genética , Nanismo/genética , Osteocondrodisplasias/genética , Osteogênese Imperfeita/genética , Fenótipo , Receptores Citoplasmáticos e Nucleares/genética , Adulto , Alelos , Condrodisplasia Punctata/diagnóstico por imagem , Condrodisplasia Punctata/patologia , Nanismo/diagnóstico por imagem , Nanismo/patologia , Feminino , Feto/patologia , Homozigoto , Humanos , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/patologia , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/patologia , Gravidez , Receptor de Lamina BRESUMO
BACKGROUND: The Canadian CT Head Rule (CCHR), the Canadian Transient Ischemic Attack (TIA) Score, and the Subarachnoid Hemorrhage (SAH) Rule have all previously demonstrated the potential to significantly standardize care and improve the management of patients in emergency departments (EDs). On the basis of user feedback, we believe that the addition of these rules to the Ottawa Rules App has the potential to increase the app's usability and user acceptability. OBJECTIVE: This study aimed to evaluate the perceived usefulness, acceptability, and uptake of the enhanced Ottawa Rules App (which now includes CCHR, TIA, and SAH Rules) among ED clinicians (medical students, residents, nurses, and physicians). METHODS: The enhanced Ottawa Rules App was publicly released for free on iOS and Android operating systems in November 2018. This study was conducted across 2 tertiary EDs in Ottawa, Canada. Posters, direct enrollment, snowball sampling, and emails were used for study recruitment. A 24-question Web-based survey was administered to participants via email, and this was used to determine user acceptability of the app and Technology Readiness Index (TRI) scores. In-app user analytics were collected to track user behavior, such as the number of app sessions, length of app sessions, frequency of rule use, and the date app was first opened. RESULTS: A total of 77 ED clinicians completed the study, including 34 nurses, 12 residents, 14 physicians, and 17 medical students completing ED rotations. The median TRI score for this group was 3.38, indicating a higher than average propensity to embrace and adopt new technologies to accomplish goals in their work or daily lives. The majority of respondents agreed or strongly agreed that the app helped participants accurately carry out the clinical rules (56/77, 73%) and that they would recommend this app to their colleagues (64/77, 83%). Feedback from study participants suggested further expansion of the app-more clinical decision rules (CDRs) and different versions of the app tailored to the clinician role. Analysis and comparison of Google Analytics data and in-app data revealed similar usage behavior among study-enrolled users and all app users globally. CONCLUSIONS: This study provides evidence that using the Ottawa Rules App (version 3.0.2) to improve and guide patient care would be feasible and widely accepted. The ability to verify self-reported user data (via a Web-based survey) against server analytics data is a notable strength of this study. Participants' continued app use and request for the addition of more CDRs warrant the further development of this app and call for additional studies to evaluate its feasibility and usability in different settings as well as assessment of clinical impact.
Assuntos
Tomada de Decisão Clínica , Serviço Hospitalar de Emergência , Aplicativos Móveis , Adulto , Canadá , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
The selective permeability of the blood-brain barrier (BBB) is controlled by tight junction-expressing brain endothelial cells. The integrity of these junctional proteins, which anchor to actin via zonula occludens (e.g., ZO-1), plays a vital role in barrier function. While disrupted junctions are linked with several neurodegenerative diseases, the mechanisms underlying disruption are not fully understood. This is largely due to the lack of appropriate models and efficient techniques to quantify edge-localized protein. Here, we developed a novel junction analyzer program (JAnaP) to semi-automate the quantification of junctional protein presentation. Because significant evidence suggests a link between myosin-II mediated contractility and endothelial barrier properties, we used the JAnaP to investigate how biochemical and physical cues associated with altered contractility influence ZO-1 presentation in brain endothelial cells. Treatment with contractility-decreasing agents increased continuous ZO-1 presentation; however, this increase was greatest on soft gels of brain-relevant stiffness, suggesting improved barrier maturation. This effect was reversed by biochemically inhibiting protein phosphatases to increase cell contractility on soft substrates. These results promote the use of brain-mimetic substrate stiffness in BBB model design and motivates the use of this novel JAnaP to provide insight into the role of junctional protein presentation in BBB physiology and pathologies.
Assuntos
Encéfalo/citologia , Células Endoteliais/fisiologia , Junções Intercelulares/fisiologia , Proteína da Zônula de Oclusão-1/fisiologia , Células Cultivadas , Humanos , FenótipoRESUMO
A 16-year-old Hispanic man was transferred to our level I paediatric trauma centre with pancreatitis. Ten days prior, he had sustained a gunshot wound to the abdomen requiring an exploratory laparotomy for repair of a traumatic left diaphragmatic injury. Additional injuries included gastric, renal, liver and pancreatic lacerations as well as a T12 burst fracture that resulted in paraplegia. Conservative management of pancreatitis was unsuccessful over the next 10 days, resulting in progressive symptoms of severe unresolved pain, nausea, emesis and rising lipase. Workup for post-traumatic, biliary and drug-associated causes of pancreatitis was negative, and no anatomical abnormalities were found on imaging. A fever workup on hospital day 10 revealed a urinary tract infection with non-typhoid Salmonella sp, and subsequent stool and imaging studies revealed salmonellosis associated with right-sided colitis and Clostridium difficile infection. Pancreatitis resolved within 48 hours following treatment of salmonellosis and Clostridium.
Assuntos
Enterocolite Pseudomembranosa/complicações , Pancreatite/complicações , Infecções por Salmonella/complicações , Ferimentos por Arma de Fogo/microbiologia , Abdome/microbiologia , Adolescente , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Clostridioides difficile/isolamento & purificação , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/tratamento farmacológico , Humanos , Masculino , Metronidazol/uso terapêutico , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Salmonella/isolamento & purificação , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológico , Sulfametoxazol/uso terapêutico , Trimetoprima/uso terapêuticoRESUMO
OBJECTIVE: The objective of this panel was to generate recommendations to promote the engagement of front-line emergency department (ED) clinicians in clinical and implementation research. METHODS: Panel members conducted semi-structured interviews with 37 Canadian adult and pediatric emergency medicine researchers to elicit barriers and facilitators to clinician engagement in research activities, and to glean strategies for promoting clinician engagement. RESULTS: Responses were organized by themes, and, based on these responses, recommendations were developed and refined in an iterative fashion by panel members. CONCLUSIONS: We offer eight recommendations to promote front-line clinician engagement in clinical research activities. Recommendations to promote clinician engagement specifically address the creation of a research-friendly culture in the ED, minimizing the burden of data collection on clinical staff through the careful design of data collection tools and the use of research staff, and communication between researchers and clinical staff to promote adherence to study protocols.
Assuntos
Pesquisa Biomédica/organização & administração , Comunicação , Medicina de Emergência , Serviço Hospitalar de Emergência/normas , Pesquisa Qualitativa , Canadá , HumanosRESUMO
OBJECTIVE: The objective of Panel 2b was to present an overview of and recommendations for the conduct of implementation trials and multicentre studies in emergency medicine. METHODS: Panel members engaged methodologists to discuss the design and conduct of implementation and multicentre studies. We also conducted semi-structured interviews with 37 Canadian adult and pediatric emergency medicine researchers to elicit barriers and facilitators to conducting these kinds of studies. RESULTS: Responses were organized by themes, and, based on these responses, recommendations were developed and refined in an iterative fashion by panel members. CONCLUSIONS: We offer eight recommendations to facilitate multicentre clinical and implementation studies, along with guidance for conducting implementation research in the emergency department. Recommendations for multicentre studies reflect the importance of local study investigators and champions, requirements for research infrastructure and staffing, and the cooperation and communication between the coordinating centre and participating sites.