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BACKGROUND: Multisite LV stimulation therapy allows for stimulation of two different left ventricular pacing vectors within a single LV lead and may improve responsiveness to cardiac resynchronization therapy (CRT). This study prospectively evaluated the safety and efficacy of the MultiPole Pacing (MPP) feature in CRT non-responder patients. METHODS AND RESULTS: CRT non-responders with a standard CRT-D indication were eligible for enrollment into the MPP Sub-Study. Patient status, NYHA classification, Patient Global Assessment (PGA), and adverse events were collected at follow-up. A clinical composite score (CCS) was determined at the 6 month follow-up visit. The primary objective was defined as the proportion of patients with an improved CCS. Safety was evaluated as freedom from MPP system related adverse events requiring additional invasive intervention to resolve. A total of 53 patients were enrolled across 26 U.S. centers. The cumulative follow-up duration was 24.1 years. CCS was improved in 35.6% of patients (p < .0001 when compared to a performance goal of 3%) after 6 months of MPP therapy. When incorporating patient feedback into a modified CCS, 60.0% of patients showed an improvement. Three patients (5.7%) experienced hospitalization for heart failure, and three patient deaths occurred over the follow-up period. No MPP system-related events were reported for an AE-free rate of 100% (95% CI 93.28% to 100.0%). CONCLUSIONS: The results of this small, non-randomized study suggest that the MPP feature is safe, and may be effective at converting a percentage of CRT non-responders to responders. Larger, randomized studies are needed to confirm this result.
Assuntos
Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , Idoso , Dispositivos de Terapia de Ressincronização Cardíaca , Feminino , Humanos , Masculino , Estudos Prospectivos , Estados UnidosRESUMO
INTRODUCTION: The novel two-lead cardiac resynchronization therapy (CRT)-DX system utilizes a floating atrial dipole on the implantable cardioverter-defibrillator lead, and when implanted with a left ventricular (LV) lead, offers a two-lead CRT system with AV synchrony. This study compared complication rates and CRT response among subjects implanted with a two-lead CRT-DX system to those subjects implanted with a standard three-lead CRT-D system. METHODS AND RESULTS: A total of 240 subjects from the Sentus QP-Extended CRT Evaluation with Quadripolar Left Ventricular Leads postapproval study were selected to identify 120 matched pairs based on similar demographic characteristics using a Greedy algorithm. The complication-free rate was evaluated as the primary endpoint. All-cause mortality, heart failure hospitalizations, device diagnostic data, New York Heart Association (NYHA) class improvement, and defibrillator therapy were evaluated from clinical data, in-office interrogations, and remote monitoring throughout the follow-up period. Complication-free survival favored the CRT-DX group with 92.5% without a major complication compared to 85.0% in the CRT-D cohort (P = .0495; 95% confidence interval: 0.1%-14.9%) over a mean follow-up of 1.3 and 1.4 years, respectively. Incidence of all-cause mortality, heart failure hospitalizations, NYHA changes at 6 months postimplant, and percent of LV pacing during CRT therapy were similar in both device cohorts. Inappropriate shocks were more frequent in the CRT-D cohort with 5.8% of subjects receiving an inappropriate shock vs 0.8% in the CRT-DX cohort. CONCLUSION: The results of this subanalysis demonstrate that the CRT-DX system can provide similar CRT responses and significantly fewer complications when compared to a similar cohort with a conventional three-lead CRT-D system.
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Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Dispositivos de Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , New York , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND: Insertable cardiac monitors are utilized for the diagnosis of arrhythmias and traditionally have been inserted within hospitals. Recent code updates allow for reimbursement of office-based insertions; however, there is limited information regarding the resources and processes required to support in-office insertions. We sought to determine the safety and feasibility of in-office insertion of the BioMonitor 2 and better understand in-office procedures, including patient selection, pre-insertion protocols, resource availability, and staff support. METHODS: Patients meeting an indication for a rhythm monitor were prospectively enrolled into this single-arm, non-randomized trial. All patients underwent insertion in an office setting. Two follow-up visits at days 7 and 90 were required. Information on adverse events, device performance, office site preparations, and resource utilization were collected. RESULTS: Eighty-two patients were enrolled at six sites. Insertion was successful in all 77 patients with an attempt. Oral anticoagulation was stopped in 20.8% of patients and continued through insertion in 23.4%, while prophylactic antibiotics were infrequently utilized (37.7% of study participants). On average, the procedure required a surgeon plus two support staff and 35 min in an office room to complete the 8.4 min insertion procedure. The mean R-wave amplitude was 0.77 mV at insertion and 0.67 mV at 90-days with low noise burden (2.7%). There were no procedure related complications. Two adverse events were reported (event rate 2.7% [95% CI 0.3, 9.5%]). CONCLUSIONS: In-office insertion of the BioMonitor 2 is safe and feasible. Devices performed well with high R-wave amplitudes and low noise burden. These results further support shifting cardiac monitor insertions to office-based locations. TRIAL REGISTRATION: clinicaltrials.gov, NCT02756338. Registered 29 April 2016.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Arritmias Cardíacas/diagnóstico , Eletrocardiografia Ambulatorial/instrumentação , Frequência Cardíaca , Telemetria/instrumentação , Adulto , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Arritmias Cardíacas/fisiopatologia , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Segurança do Paciente , Valor Preditivo dos Testes , Vigilância de Produtos Comercializados , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Estados UnidosRESUMO
Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models. In this study, we unify these previous findings by demonstrating that TREM2 deficiency ameliorates amyloid pathology early, but exacerbates it late in disease progression in the APPPS1-21 mouse model of AD. We also demonstrate that TREM2 deficiency decreases plaque-associated myeloid cell accumulation by reducing cell proliferation, specifically late in pathology. In addition, TREM2 deficiency reduces myeloid cell internalization of amyloid throughout pathology, but decreases inflammation-related gene transcript levels selectively late in disease progression. Together, these results suggest that TREM2 plays distinct functional roles at different stages in AD pathology. SIGNIFICANCE STATEMENT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder and there are currently no effective treatments that modify disease progression. However, the recent identification of genetic risk factors for AD promises to provide new insight into AD biology and possible new therapeutic targets. Among these risk factors, variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2) confer greatly elevated risk for developing the disease. We demonstrate that TREM2 deficiency has opposing effects on AD-related pathologies at early and late stages of disease progression, unifying previous work in the field. In addition, we examine how TREM2 affects the function of the brain immune cell populations in which it is expressed throughout disease progression to understand possible mechanisms underlying its differential impacts on pathology.
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Doença de Alzheimer/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Glicoproteínas de Membrana/deficiência , Receptores Imunológicos/deficiência , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Knockout , Receptores Imunológicos/genéticaRESUMO
BACKGROUND: Fractalkine (CX3CL1) and its receptor (CX3CR1) play an important role in regulating microglial function. We have previously shown that Cx3cr1 deficiency exacerbated tau pathology and led to cognitive impairment. However, it is still unclear if the chemokine domain of the ligand CX3CL1 is essential in regulating neuronal tau pathology. METHODS: We used transgenic mice lacking endogenous Cx3cl1 (Cx3cl1-/-) and expressing only obligatory soluble form (with only chemokine domain) and lacking the mucin stalk of CX3CL1 (referred to as Cx3cl1105Δ mice) to assess tau pathology and behavioral function in both lipopolysaccharide (LPS) and genetic (hTau) mouse models of tauopathy. RESULTS: First, increased basal tau levels accompanied microglial activation in Cx3cl1105Δ mice compared to control groups. Second, increased CD45+ and F4/80+ neuroinflammation and tau phosphorylation were observed in LPS, hTau/Cx3cl1-/-, and hTau/Cx3cl1105Δ mouse models of tau pathology, which correlated with impaired spatial learning. Finally, microglial cell surface expression of CX3CR1 was reduced in Cx3cl1105Δ mice, suggesting enhanced fractalkine receptor internalization (mimicking Cx3cr1 deletion), which likely contributes to the elevated tau pathology. CONCLUSIONS: Collectively, our data suggest that overexpression of only chemokine domain of CX3CL1 does not protect against tau pathology.
Assuntos
Quimiocina CX3CL1/genética , Regulação da Expressão Gênica/genética , Microglia/metabolismo , Tauopatias/patologia , Animais , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Quimiocina CX3CL1/metabolismo , Transtornos Cognitivos/etiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Mutação/genética , Tauopatias/complicações , Tauopatias/genética , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2(V617F) status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mielofibrose Primária/terapia , Adulto , Idoso , Análise de Variância , Soro Antilinfocitário/uso terapêutico , Doadores de Sangue , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histocompatibilidade , Humanos , Janus Quinase 2/genética , Estimativa de Kaplan-Meier , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mutação , Mielofibrose Primária/genética , Estudos Prospectivos , Irmãos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Vidarabina/análogos & derivados , Vidarabina/uso terapêuticoRESUMO
The phenomenon, "huddle moments," can be described as a preparatory briefing among healthcare providers for the purpose of collaborating, exchanging information, and bringing awareness to patient safety concerns. A historical background of huddle communication is described and a systematic literature review was conducted on preoperative briefing and huddle communication. The article also describes a need for increased interprofessional collaboration education in anesthesia and a need for leadership to support initiatives that improve patient safety. The purpose of this article is to provide a systematic review of huddle communication and give future evidence-based recommendations on how the huddle can be used in healthcare as well as how to roll out use of the HUDDLE acronym: Healthcare, Utilizing, Deliberate, Discussion, Linking, Events.
Assuntos
Anestesiologia/métodos , Comportamento Cooperativo , Relações Interprofissionais , Planejamento de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Segurança do Paciente , Cuidados Pré-Operatórios/métodos , Comunicação , Humanos , Recursos Humanos de Enfermagem Hospitalar , Auxiliares de Cirurgia , MédicosRESUMO
AIMS: For most elderly pacemaker patients, evaluation of rate-adaptive pacing using treadmill and bicycle tests is impractical and not representative of typical daily activities. This study was designed to compare the performance and physiological response of the closed-loop stimulation (CLS) rate-adaptive sensor to accelerometer (XL) and no rate sensor (DDD) during typical daily activity testing. METHODS AND RESULTS: Subjects recently implanted with a Cylos pacemaker completed timed activities of daily life testing, which included walking, sweeping, and standing from a seated position. Activity performance and physiological response from each sensor mode was evaluated for subjects requiring ≥80% pacing. Overall, 74 subjects needed ≥80% pacing during at least one test. An increase in the area swept (CLS vs. XL, 1.67 m(2) difference, P = 0.009; CLS vs. DDD, 1.59 m(2) difference, P = 0.025) and a decrease in the prevalence of orthostatic hypotension (OH) after standing 1 min (CLS vs. XL, odds ratio = 0.16, P = 0.006; CLS vs. DDD, odds ratio = 0.18, P = 0.012) was observed in the CLS mode as compared with XL and DDD. No statistical difference in walk distance was observed between CLS and XL or CLS and DDD. CONCLUSION: In acute testing, as compared with XL and DDD, CLS provides a more physiological response during the performance of activities of daily living for subjects with ≥80% pacing. This is clinically reflected in better performance during the sweep test as well as a decrease in the prevalence of OH in our elderly population. Clinicaltrials.gov identifier: NCT00355797.
Assuntos
Actigrafia/métodos , Atividades Cotidianas , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/prevenção & controle , Estimulação Cardíaca Artificial/métodos , Teste de Esforço/métodos , Monitorização Ambulatorial/métodos , Idoso , Feminino , Humanos , Masculino , Atividade Motora , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Estados UnidosRESUMO
With a focus on safety, these nurses manage all infusion needs.
Assuntos
Recursos Humanos de Enfermagem Hospitalar , Enfermagem , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: TP53-mutated acute myeloid leukaemia is associated with poor outcomes. Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator. We aimed to evaluate the combination of eprenetapopt and venetoclax with or without azacitidine in patients with TP53-mutated acute myeloid leukaemia. METHODS: This phase 1, multicentre, open-label, dose-finding and cohort expansion study was done at eight academic research hospitals in the USA. Inclusion criteria were age of at least 18 years; at least one pathogenic TP53 mutation; treatment-naive acute myeloid leukaemia according to the 2016 WHO classification; an ECOG performance status of 0-2; and a life expectancy of at least 12 weeks. In dose-finding cohort 1 patients received previous therapy with hypomethylating agents for myelodysplastic syndromes. In dose-finding cohort 2, previous use of hypomethylating agents was not permitted. Treatment cycles were 28 days. Patients in cohort 1 received intravenous eprenetapopt 4·5 g/day on days 1-4 and oral venetoclax 400 mg/day on days 1-28; those in cohort 2 also received subcutaneous or intravenous azacitidine 75 mg/m2 on days 1-7. The expansion part of the study proceeded with patients enrolled as in cohort 2. Primary endpoints were safety in all cohorts (assessed in patients receiving at least one dose of assigned treatment) and complete response in the expansion cohort (assessed in patients who completed at least one treatment cycle and had at least one post-treatment clinical response assessment). The trial is registered with ClinicalTrials.gov, NCT04214860, and is complete. FINDINGS: Between Jan 3, 2020, and July 22, 2021, 49 patients were enrolled across all cohorts. Six patients were initially enrolled into each of dose-finding cohorts 1 and 2; after no dose-limiting toxicities were observed, cohort 2 was expanded to enrol an additional 37 patients. The median age was 67 years (IQR 59-73). 24 (49%) of 49 patients were female and 25 (51%) male, and 40 (82%) were White. At data cutoff (Oct 1, 2021), the median length of follow-up was 9·5 months (IQR 6·1-11·5). No dose-limiting toxicities were recorded and the recommended phase 2 dose for eprenetapopt combinations was 4·5 g/day on days 1-4. Across all patients, adverse events of grade 3 or worse occurring in at least 20% of patients were febrile neutropenia (23 [47%] of 49 patients), thrombocytopenia (18 [37%] patients), leukopenia (12 [25%] patients), and anaemia (11 [22%] patients). Treatment-related serious adverse events occurred in 13 (27%) of 49 patients and there was one (2%) treatment-related death (sepsis). 25 (64%, 95% CI 47-79) of 39 patients had an overall response with eprenetapopt and venetoclax with azacytidine; 15 (38%, 23-55) had a complete response. INTERPRETATION: Eprenetapopt and venetoclax with azacitidine had an acceptable safety profile and encouraging activity, supporting further frontline evaluation of this combination in the treatment of TP53-mutated acute myeloid leukaemia. FUNDING: Aprea Therapeutics.
Assuntos
Leucemia Mieloide Aguda , Trombocitopenia , Idoso , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética , Pessoa de Meia-IdadeRESUMO
Matrix metalloproteinases (MMPs) are widely hypothesized to regulate signaling events through processing of extracellular matrix (ECM) molecules. We previously demonstrated that membrane-associated Mmp2 is expressed in exit glia and contributes to motor axon targeting. To identify possible substrates, we undertook a yeast interaction screen for Mmp2-binding proteins and identified the novel ECM protein faulty attraction (Frac). Frac encodes a multidomain extracellular protein rich in epidermal growth factor (EGF) and calcium-binding EGF domains, related to the vertebrate Fibrillin and Fibulin gene families. It is expressed in mesodermal domains flanking Mmp2-positive glia. The juxtaposition of Mmp2 and Frac proteins raises the possibility that Frac is a proteolytic target of Mmp2. Consistent with this hypothesis, levels of full-length Frac are increased in Mmp2 loss-of-function (LOF) and decreased in Mmp2 gain-of-function (GOF) embryos, indicating that Frac cleavage is Mmp2 dependent. To test whether frac is necessary for axon targeting, we characterized guidance in frac LOF mutants. Motor axons in frac LOF embryos are loosely associated and project ectopically, a phenotype essentially equivalent to that of Mmp2 LOF. The phenotypic similarity between enzyme and substrate mutants argues that Mmp2 activates Frac. In addition, Mmp2 overexpression pathfinding phenotypes depend on frac activity, indicating that Mmp2 is genetically upstream of frac. Last, overexpression experiments suggest that Frac is unlikely to have intrinsic signaling activity, raising the possibility that an Mmp2-generated Frac fragment acts as a guidance cue cofactor. Indeed, we present genetic evidence that Frac regulates a non-canonical LIM kinase 1-dependent bone morphogenetic protein signaling pathway in motoneurons necessary for axon pathfinding during embryogenesis.
Assuntos
Axônios/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Metaloproteinase 2 da Matriz/metabolismo , Neurônios Motores/citologia , Transdução de Sinais/fisiologia , Fatores Etários , Animais , Animais Geneticamente Modificados , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Ligação ao Cálcio/genética , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Embrião não Mamífero , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Sequências Hélice-Alça-Hélice/genética , Humanos , Quinases Lim/genética , Quinases Lim/metabolismo , Metaloproteinase 2 da Matriz/genética , Proteínas dos Microfilamentos/metabolismo , Modelos Biológicos , Neurônios Motores/metabolismo , Mutação/genética , Neuroglia/metabolismo , Oligodesoxirribonucleotídeos Antissenso/farmacologia , RNA/metabolismo , Transdução de Sinais/genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry represents a revolution in the rapid identification of bacterial and fungal pathogens in the clinical microbiology laboratory. Recently, MALDI-TOF has been applied directly to positive blood culture bottles for the rapid identification of pathogens, leading to reductions in turnaround time and potentially beneficial patient impacts. The development of a commercially available extraction kit (Bruker Sepsityper) for use with the Bruker MALDI BioTyper has facilitated the processing required for identification of pathogens directly from positive from blood cultures. We report the results of an evaluation of the accuracy, cost, and turnaround time of this method for 61 positive monomicrobial and 2 polymicrobial cultures representing 26 species. The Bruker MALDI BioTyper with the Sepsityper gave a valid (score, >1.7) identification for 85.2% of positive blood cultures with no misidentifications. The mean reduction in turnaround time to identification was 34.3 h (P < 0.0001) in the ideal situation where MALDI-TOF was used for all blood cultures and 26.5 h in a more practical setting where conventional identification or identification from subcultures was required for isolates that could not be directly identified by MALDI-TOF. Implementation of a MALDI-TOF-based identification system for direct identification of pathogens from blood cultures is expected to be associated with a marginal increase in operating costs for most laboratories. However, the use of MALDI-TOF for direct identification is accurate and should result in reduced turnaround time to identification.
Assuntos
Bacteriemia/diagnóstico , Sangue/microbiologia , Fungemia/diagnóstico , Técnicas Microbiológicas/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Bacteriemia/microbiologia , Custos e Análise de Custo , Fungemia/microbiologia , Humanos , Técnicas Microbiológicas/economia , Manejo de Espécimes/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/economia , Fatores de TempoRESUMO
OBJECTIVE: Our objective was to demonstrate that, despite recognition by both the gastroenterology and headache communities, abdominal migraine (AM) is an under-diagnosed cause of chronic, recurrent, abdominal pain in childhood in the USA. BACKGROUND: Chronic, recurrent abdominal pain occurs in 9-15% of all children and adolescents. After exclusion of anatomic, infectious, inflammatory, or other metabolic causes, "functional abdominal pain" is the most common diagnosis of chronic, idiopathic, abdominal pain in childhood. Functional abdominal pain is typically categorized into one, or a combination of, the following 4 groups: functional dyspepsia, irritable bowel syndrome, AM, or functional abdominal pain syndrome. International Classification of Headache Disorders--(ICHD-2) defines AM as an idiopathic disorder characterized by attacks of midline, moderate to severe abdominal pain lasting 1-72 hours with vasomotor symptoms, nausea and vomiting, and included AM among the "periodic syndromes of childhood that are precursors for migraine." Rome III Gastroenterology criteria (2006) separately established diagnostic criteria and confirmed AM as a well-defined cause of recurrent abdominal pain. METHODS: Following institutional review board approval, a retrospective chart review was conducted on patients referred to an academic pediatric gastroenterology practice with the clinical complaint of recurrent abdominal pain. ICHD-2 criteria were applied to identify the subset of children fulfilling criteria for AM. Demographics, diagnostic evaluation, treatment regimen and outcomes were collected. RESULTS: From an initial cohort of 600 children (ages 1-21 years; 59% females) with recurrent abdominal pain, 142 (24%) were excluded on the basis of their ultimate diagnosis. Of the 458 patients meeting inclusion criteria, 1824 total patient office visits were reviewed. Three hundred eighty-eight (84.6%) did not meet criteria for AM, 20 (4.4%) met ICHD-2 formal criteria for AM and another 50 (11%) had documentation lacking at least 1 criterion, but were otherwise consistent with AM (probable AM). During the observation period, no children seen in this gastroenterology practice had received a diagnosis of AM. CONCLUSION: Among children with chronic, idiopathic, recurrent abdominal pain, AM represents about 4-15%. Given the spectrum of treatment modalities now available for pediatric migraine, increased awareness of cardinal features of AM by pediatricians and pediatric gastroenterologists may result in improved diagnostic accuracy and early institution of both acute and preventative migraine-specific treatments.
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Dor Abdominal/complicações , Dor Abdominal/epidemiologia , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Dor Abdominal/classificação , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Transtornos de Enxaqueca/classificação , Prevalência , Estados Unidos/epidemiologia , Adulto JovemRESUMO
There remains a large gender imbalance in the science, technology, engineering and mathematics (STEM) workforce deriving from a leaky pipeline where women start losing interest and confidence in science and engineering as early as primary school. To address this disparity, the Science Research & Engineering Program (SREP) at Hathaway Brown School was established in 1998 to engage and expose their all-female high school students to STEM fields through an internship-like multi-year research experience at partnering institutions. We compare data from existing Hathaway Brown School SREP alumnae records from 1998-2018 (n = 495) to Non-SREP students and national datasets (National Center for Educational Statistics, National Science Foundation, and US Census data) to assess how SREP participation may influence persistence in the STEM pipeline and whether SREP alumnae attribute differences in these outcomes to the confidence and skill sets they learned from the SREP experience. The results reveal that women who participate in the SREP are more likely to pursue a major in a STEM field and continue on to a STEM occupation compared to non-SREP students, national female averages, and national subsets. Participants attribute their outcomes to an increase in confidence, establishment of technical and professional skills, and other traits strengthened through the SREP experience. These data suggest that implementing similar experiential programs for women in science and engineering at the high school stage could be a promising way to combat the remaining gender gap in STEM fields.
Assuntos
Engenharia/estatística & dados numéricos , Aprendizagem/fisiologia , Ciência/estatística & dados numéricos , Sexismo , Adolescente , Adulto , Engenharia/normas , Feminino , Humanos , Estudos Longitudinais , Masculino , Matemática/estatística & dados numéricos , Instituições Acadêmicas , Ciência/normas , Estudantes , Tecnologia/estatística & dados numéricos , Recursos Humanos , Adulto JovemRESUMO
BACKGROUND: Cardiac implantable electronic devices (CIED)-ie, pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices-have recently been designed to allow for patients to safely undergo magnetic resonance imaging (MRI) when specific programming is implemented. MRI AutoDetect is a feature that automatically switches CIED's programming into and out of an MR safe mode when exposed to an MRI environment. OBJECTIVE: The purpose was to analyze de-identified daily remote transmission data to characterize the utilization of the MRI AutoDetect feature. METHODS: Home Monitoring transmission data collected from MRI AutoDetect-capable devices were retrospectively analyzed to determine the workflow and usage in patients experiencing an MRI using the MRI AutoDetect feature. RESULTS: Among 48,756 capable systems, 2197 devices underwent an MRI using the MRI AutoDetect feature. In these 2197 devices, the MRI AutoDetect feature was used a total of 2806 times with an average MRI exposure of 40.83 minutes. The majority (88.9%) of MRI exposures occurred on the same day as the MRI AutoDetect programming. A same day post-MRI exposure follow-up device interrogation was performed 8.6% of the time. A device-related complaint occurred within 30 days of the MRI exposure in 0.25% of MRI exposures using MRI AutoDetect but with no adverse clinical outcome. CONCLUSION: As a result of automation in device programming, the MRI AutoDetect feature eliminated post-MRI device reprogramming in 91.4% of MRI exposures and, while less frequent, allowed for pre-MRI interrogations prior to the day of the MRI exposure-reducing resource utilization and creating workflow flexibility.
RESUMO
In Canada, responsibility for corrections is divided between federal, provincial and territorial governments, with nurses being the largest group of healthcare professionals working in correctional institutions (penitentiaries, jails, prisons, correctional centres and secure correctional treatment centres) across the country. Correctional institutions are among the most challenging workplace settings for nurses, as they face competing tensions between the provision of quality care and strict security requirements for safety. They also experience unique workforce issues with high reports of burnout and emotional exhaustion. Nursing leadership at all levels of the correctional system is critical in creating work environments that optimize workplace well-being and minimize burnout. The purpose of this paper is to discuss the role of nursing leadership in facilitating and enabling a healthy workforce in corrections. Minimal research has examined leadership and healthy work environments in correctional institutions. Several authors have, however, discussed transformational leadership as a strategy to positively influence correctional nursing practice. In this article, we expand on this previous work to describe the full range leadership model and how it can be used to form the foundation of effective leadership and support the creation of healthy work environments in the correctional context.
Assuntos
Mão de Obra em Saúde/normas , Liderança , Prisões/estatística & dados numéricos , Canadá , Mão de Obra em Saúde/estatística & dados numéricos , Humanos , Satisfação no Emprego , Enfermagem/métodosRESUMO
BACKGROUND: Outcomes of patients with nonischemic cardiomyopathy and low ejection fraction implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D), especially in contemporary, real-life cohorts, are not fully understood. OBJECTIVE: We aimed to better characterize outcomes of death and ventricular tachyarrhythmias in patients with nonischemic cardiomyopathy, implanted with an ICD or CRT-D, and specifically assess differences by sex. METHODS: The AnaLysIs of Both Sex and Device Specific FactoRs on Outcomes in PAtients with Non-Ischemic Cardiomyopathy (BIO-LIBRA) study was designed to prospectively assess outcomes of device-treated ventricular tachyarrhythmias and all-cause mortality events in nonischemic cardiomyopathy patients, indicated for an ICD or CRT-D implantation for the primary prevention of sudden cardiac death (SCD), with a specific focus on sex differences. We will enroll a total of 1000 subjects across 50 U.S. sites and follow patients for up to 3 years. RESULTS: The primary objective of BIO-LIBRA is to evaluate the combined risk of all-cause mortality and treated ventricular tachycardia (VT) or ventricular fibrillation (VF) events by subject sex and by implanted device type. We will also assess all-cause mortality, VT or VF alone, cardiac death, and SCD in the total cohort, as well as by subject sex and by the implanted device type. In addition, the previously validated Seattle Proportional Risk Model (SPRM) will be used to compare the SPRM predicted incidence of SCD to the observed incidence. CONCLUSIONS: The BIO-LIBRA study will provide novel and contemporary information regarding outcomes in patients with a NICM who receive a defibrillator.
RESUMO
Functional and biochemical data have suggested a role for the cytochrome P450 arachidonate monooxygenases in the pathophysiology of hypertension, a leading cause of cardiovascular, cerebral, and renal morbidity and mortality. We show here that disruption of the murine cytochrome P450, family 4, subfamily a, polypeptide 10 (Cyp4a10) gene causes a type of hypertension that is, like most human hypertension, dietary salt sensitive. Cyp4a10-/- mice fed low-salt diets were normotensive but became hypertensive when fed normal or high-salt diets. Hypertensive Cyp4a10-/- mice had a dysfunctional kidney epithelial sodium channel and became normotensive when administered amiloride, a selective inhibitor of this sodium channel. These studies (a) establish a physiological role for the arachidonate monooxygenases in renal sodium reabsorption and blood pressure regulation, (b) demonstrate that a dysfunctional Cyp4a10 gene causes alterations in the gating activity of the kidney epithelial sodium channel, and (c) identify a conceptually novel approach for studies of the molecular basis of human hypertension. It is expected that these results could lead to new strategies for the early diagnosis and clinical management of this devastating disease.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Hipertensão , Rim/metabolismo , Canais de Sódio/metabolismo , Sódio na Dieta , Amilorida/metabolismo , Animais , Ácidos Araquidônicos/química , Ácidos Araquidônicos/metabolismo , Pressão Sanguínea/fisiologia , Família 2 do Citocromo P450 , Eletrofisiologia , Canais Epiteliais de Sódio , Feminino , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Masculino , Camundongos , Camundongos Knockout , Pirimidinas/metabolismo , Sódio/metabolismo , Bloqueadores dos Canais de Sódio/metabolismo , Canais de Sódio/genéticaRESUMO
BACKGROUND: Correctional nursing requires a strong knowledge base with access to continuing education (CE) to maintain and enhance competencies. Nurses working in provincial prisons have reported many challenges in accessing CE, with online learning being identified as a potential solution. Limited research was found, however, which examined the correctional context in the development and delivery of online learning for nurses. The purpose of this study was to develop an online educational intervention tailored to correctional nurses and determine the feasibility and acceptability of implementing the intervention in a provincial prison context. METHODS: A sequential mixed methods study was conducted. Participants included nurses from three correctional settings in the province of Ontario, Canada. Semistructured interviews examined contextual factors and educational needs. Delphi surveys determined the educational topic. Preintervention and postintervention questionnaires examined the context, educational content, and intervention's acceptability and feasibility. RESULTS: The online intervention focused on mental health and addictions with two 30-minute webinars delivered back-to-back over 15 weeks. Respondents expressed satisfaction with the convenience of online learning at work using short webinars, as well as the topics, relevance of information, and teaching materials, but dissatisfaction with presentation style. The feasibility of the intervention was limited by access to technology, time to attend, education space, and comfort with technology. DISCUSSION: The findings from this study provide insight to guide the future development of online CE for correctional nurses. If changes are made within correctional facilities in collaboration with nurses and managers, online learning holds the potential to facilitate access to ongoing professional development.
Assuntos
Instrução por Computador , Internet , Recursos Humanos de Enfermagem , Prisões , Desenvolvimento de Pessoal , Técnica Delphi , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Ontário , Especialidades de EnfermagemRESUMO
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer's disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2's involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45(hi)Ly6C(+) myeloid cells, but not on P2RY12(+) parenchymal microglia. In AD mice deficient for TREM2, the CD45(hi)Ly6C(+) macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2(+) macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.