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1.
JCI Insight ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513547

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) is the visceral fat depot of the heart. Inflammation of EAT is thought to contribute to coronary artery disease (CAD). Therefore, we hypothesized that the EAT of patients with CAD would have increased inflammatory gene expression compared to controls without CAD. METHODS: 26 patients referred for cardiac surgery with (n=13) or without CAD (n=13) were consented. Samples of EAT and subcutaneous adipose tissue (SAT) were obtained at the time of surgery. Gene expression analysis was performed using Affymetrix Human Gene 1.0 ST arrays. Differential regulation was defined as a 1.5 fold change (ANOVA p<0.05). RESULTS: When comparing SAT and EAT of controls, 693 genes were differentially expressed. 805 genes were differentially expressed between SAT and EAT in cases. Expression of 326 genes was different between EAT of cases and controls; expression of 14 genes was increased in cases, while 312 were increased in controls. qRT-PCR confirmed that there was no difference in expression of major inflammatory genes (CCL2, CCR2, TNFα, IL6, IL8, PAI1) between cases and controls. Immunohistochemistry demonstrated that there were more macrophages in EAT than SAT, but that there was no difference in the number or activation state between cases and controls. CONCLUSION: In contrast to prior studies, we did not find increased inflammatory gene expression in the EAT of patients with CAD in comparison to controls without CAD. We conclude that specific adipose tissue organ, rather than CAD status, is responsible for the majority of differential gene expression.

2.
Diagn Microbiol Infect Dis ; 95(1): 20-24, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129008

RESUMO

Diagnostic tests for Clostridioides difficile infection (CDI) lack either specificity (nucleic acid amplification tests) or sensitivity (enzyme immunoassays; EIAs). The performance of the Singulex Clarity® C. diff toxins A/B assay was compared to cell cytotoxicity neutralization assay. Testing was also performed using an EIA for glutamate dehydrogenase (GDH) and C. difficile toxins A and B (C. Diff Quik Chek Complete®), polymerase chain reaction (PCR) (BD MAX™ Cdiff Assay), and 2 multistep algorithms: algorithm 1 (discordant GDH/toxin results arbitrated by PCR) and algorithm 2 (PCR-positive samples tested with toxin EIA). The Clarity assay and PCR both had 97% sensitivity, while specificity was 100% for Clarity and 79% for PCR. Algorithm 1 yielded 41% discordant results, and both toxin EIA and algorithm 2 had 58% sensitivity. Median toxin concentrations, as measured by the Clarity C. difficile toxin assay, were 3590, 11.5, 0.4, and 0 pg/mL for GDH+/toxin+, GDH+/toxin-/PCR+, GDH+/toxin-/PCR-, and GDH-/toxin- samples, respectively (P < 0.001). The Clarity assay may offer a single-test solution for CDI.

3.
JAMA ; 321(18): 1788-1798, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31087023

RESUMO

Importance: Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. Objectives: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery. Design, Setting, and Participants: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations. Exposures: Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. Main Outcomes and Measures: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications. Results: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy. Conclusions and Relevance: Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.


Assuntos
Doenças Cardiovasculares/etiologia , Complicações Pós-Operatórias/etiologia , Apneia Obstrutiva do Sono/complicações , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Idoso , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Hipóxia/complicações , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polissonografia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico
4.
J Clin Microbiol ; 56(11)2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30158195

RESUMO

Current tests for the detection of Clostridioides (formerly Clostridium) difficile free toxins in feces lack sensitivity, while nucleic acid amplification tests lack clinical specificity. We have evaluated the Singulex Clarity C. diff toxins A/B assay (currently in development), an automated and rapid ultrasensitive immunoassay powered by single-molecule counting technology, for detection of C. difficile toxin A (TcdA) and toxin B (TcdB) in stool. The analytical sensitivity, analytical specificity, repeatability, and stability of the assay were determined. In a clinical evaluation, frozen stool samples from 311 patients with suspected C. difficile infection were tested with the Clarity C. diff toxins A/B assay, using an established cutoff value. Samples were tested with the Xpert C. difficile/Epi assay, and PCR-positive samples were tested with an enzyme immunoassay (EIA) (C. Diff Quik Chek Complete). EIA-negative samples were further tested with a cell cytotoxicity neutralization assay. The limits of detection for TcdA and TcdB were 0.8 and 0.3 pg/ml in buffer and 2.0 and 0.7 pg/ml in stool, respectively. The assay demonstrated reactivity to common C. difficile strains, did not show cross-reactivity to common gastrointestinal pathogens, was robust against common interferents, allowed detection in fresh and frozen stool samples and in samples after three freeze-thaw cycles, and provided results with high reproducibility. Compared to multistep PCR and toxin-testing procedures, the Singulex Clarity C. diff toxins A/B assay yielded 97.7% sensitivity and 100% specificity. The Singulex Clarity C. diff toxins A/B assay is ultrasensitive and highly specific and may offer a standalone solution for rapid detection and quantitation of free toxins in stool.

5.
Nature ; 545(7655): 505-509, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28514442

RESUMO

The physiology of a cell can be viewed as the product of thousands of proteins acting in concert to shape the cellular response. Coordination is achieved in part through networks of protein-protein interactions that assemble functionally related proteins into complexes, organelles, and signal transduction pathways. Understanding the architecture of the human proteome has the potential to inform cellular, structural, and evolutionary mechanisms and is critical to elucidating how genome variation contributes to disease. Here we present BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein-coding genes from the human genome, and constitutes, to our knowledge, the largest such network so far. With more than 56,000 candidate interactions, BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins while enhancing network-based analyses of domain associations, subcellular localization, and co-complex formation. Unsupervised Markov clustering of interacting proteins identified more than 1,300 protein communities representing diverse cellular activities. Genes essential for cell fitness are enriched within 53 communities representing central cellular functions. Moreover, we identified 442 communities associated with more than 2,000 disease annotations, placing numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds previous experimentally derived interaction networks in depth and breadth, and will be a valuable resource for exploring the biology of incompletely characterized proteins and for elucidating larger-scale patterns of proteome organization.


Assuntos
Bases de Dados de Proteínas , Doença , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma/metabolismo , Fenômenos Fisiológicos Celulares/genética , Genoma Humano , Humanos , Espaço Intracelular/metabolismo , Cadeias de Markov , Espectrometria de Massas , Anotação de Sequência Molecular , Fases de Leitura Aberta , Proteoma/análise , Proteoma/química , Proteoma/genética
6.
Mol Syst Biol ; 12(4): 865, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27107014

RESUMO

In cellular systems, biophysical interactions between macromolecules underlie a complex web of functional interactions. How biophysical and functional networks are coordinated, whether all biophysical interactions correspond to functional interactions, and how such biophysical-versus-functional network coordination is shaped by evolutionary forces are all largely unanswered questions. Here, we investigate these questions using an "inter-interactome" approach. We systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter-interactome network. After a billion years of evolutionary divergence, the yeast and human proteomes are still capable of forming a biophysical network with properties that resemble those of intra-species networks. Although substantially reduced relative to intra-species networks, the levels of functional overlap in the yeast-human inter-interactome network uncover significant remnants of co-functionality widely preserved in the two proteomes beyond human-yeast homologs. Our data support evolutionary selection against biophysical interactions between proteins with little or no co-functionality. Such non-functional interactions, however, represent a reservoir from which nascent functional interactions may arise.


Assuntos
Proteínas Fúngicas/metabolismo , Mapeamento de Interação de Proteínas/métodos , Proteoma/metabolismo , Biologia Computacional/métodos , Bases de Dados de Proteínas , Evolução Molecular , Humanos
7.
Cell ; 164(4): 805-17, 2016 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-26871637

RESUMO

While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms" are functionally divergent (i.e., "functional alloforms").


Assuntos
Processamento Alternativo , Isoformas de Proteínas/metabolismo , Proteoma/metabolismo , Animais , Clonagem Molecular , Evolução Molecular , Humanos , Modelos Moleculares , Fases de Leitura Aberta , Domínios e Motivos de Interação entre Proteínas , Mapas de Interação de Proteínas , Proteoma/análise
8.
Cell ; 162(2): 425-440, 2015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-26186194

RESUMO

Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors.


Assuntos
Mapas de Interação de Proteínas , Proteômica/métodos , Esclerose Amiotrófica Lateral/genética , Humanos , Espectrometria de Massas , Mapeamento de Interação de Proteínas , Proteínas/química , Proteínas/isolamento & purificação , Proteínas/metabolismo
9.
Acad Med ; 90(10): 1340-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26222322

RESUMO

The service line (SL) model has been proven to help shift health care toward value-based services, which is characterized by coordinated, multidisciplinary, high-quality, and cost-effective care. However, academic medical centers struggle with how to effectively set up SL structures that overcome the organizational and cultural challenges associated with simultaneously delivering the highest-value care for the patient and advancing the academic mission. In this article, the authors examine the evolution of UMass Memorial Health Care's heart and vascular service line (HVSL) from 2006 to 2011 and describe the impact on its success of multiple strategic decisions. These include key academic physician leadership recruitments and engagement via a matrixed governance and management model; development of multidisciplinary teams; empowerment of SL leadership through direct accountability and authority over programs and budgets; joint educational and training programs; incentives for academic achievement; and co-localization of faculty, personnel, and facilities. The authors also explore the barriers to success, including the need to overcome historical departmental-based silos, cultural and training differences among disciplines, confusion engendered by a matrixed reporting structure, and faculty's unfamiliarity with the financial and organizational skills required to operate a successful SL. Also described here is the impact that successful implementation of the SL has on creating high-quality services, increased profitability, and contribution to the financial stability and academic achievement of the academic medical center.


Assuntos
Centros Médicos Acadêmicos/organização & administração , Cardiologia/organização & administração , Administração de Serviços de Saúde , Serviços de Saúde/economia , Qualidade da Assistência à Saúde , Cirurgia Torácica/organização & administração , Centros Médicos Acadêmicos/economia , Centros Médicos Acadêmicos/normas , Cardiologia/economia , Cardiologia/normas , Procedimentos Cirúrgicos Cardiovasculares , Análise Custo-Benefício , Serviços de Saúde/normas , Humanos , Massachusetts , Cirurgia Torácica/economia , Cirurgia Torácica/normas
10.
Age Ageing ; 44(1): 143-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25355620

RESUMO

BACKGROUND: home visits and telephone calls are two often used approaches in transitional care, but their differential economic effects are unknown. OBJECTIVE: to examine the differential economic benefits of home visits with telephone calls and telephone calls only in transitional discharge support. DESIGN: cost-effectiveness analysis conducted alongside a randomised controlled trial (RCT). PARTICIPANTS: patients discharged from medical units randomly assigned to control (control, N = 210), home visits with calls (home, N = 196) and calls only (call, N = 204). METHODS: cost-effectiveness analyses were conducted from the societal perspective comparing monetary benefits and quality-adjusted life years (QALYs) gained. RESULTS: the home arm was less costly but less effective at 28 days and was dominating (less costly and more effective) at 84 days. The call arm was dominating at both 28 and 84 days. The incremental QALY for the home arm was -0.0002/0.0008 (28/84 days), and the call arm was 0.0022/0.0104 (28/84 days). When the three groups were compared, the call arm had a higher probability being cost-effective at 84 days but not at 28 days (home: 53%, call: 35% (28 days) versus home: 22%, call: 73% (84 days)) measuring against the NICE threshold of £20,000. CONCLUSION: the original RCT showed that the bundled intervention involving home visits and calls was more effective than calls only in the reduction of hospital readmissions. This study adds a cost perspective to inform policymakers that both home visits and calls only are cost-effective for transitional care support, but calls only have a higher chance of being cost-effective for a sustained period after intervention.


Assuntos
Continuidade da Assistência ao Paciente/economia , Custos de Cuidados de Saúde , Visita Domiciliar/economia , Alta do Paciente , Telefone/economia , Análise Custo-Benefício , Hong Kong , Humanos , Tempo de Internação/economia , Modelos Econômicos , Readmissão do Paciente/economia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
11.
Heart Rhythm ; 12(1): 3-10, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25257092

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are associated with cardiovascular disease and control gene expression and are detectable in the circulation. OBJECTIVE: The purpose of this study was to test the hypothesis that circulating miRNAs may be associated with atrial fibrillation (AF). METHODS: Using a prospective study design powered to detect subtle differences in miRNAs, we quantified plasma expression of 86 miRNAs by high-throughput quantitative reverse transcriptase-polymerase chain reaction in 112 participants with AF and 99 without AF. To examine parallels between cardiac and plasma miRNA profiles, we quantified atrial tissue and plasma miRNA expression using quantitative reverse transcriptase-polymerase chain reaction in 31 participants undergoing surgery. We also explored the hypothesis that lower AF burden after ablation would be reflected in the circulating blood pool by examining change in plasma miRNAs after AF ablation (n = 47). RESULTS: Mean age of the cohort was 59 years; 58% of participants were men. Plasma miRs-21 and 150 were 2-fold lower in participants with AF than in those without AF after adjustment (P ≤.0006). Plasma levels of miRs-21 and 150 also were lower in participants with paroxysmal AF than in those with persistent AF (P <.05). Expression of miR-21, but not of miR-150, was lower in atrial tissue from patients with AF than in those without AF (P <.05). Plasma levels of miRs-21 and 150 increased 3-fold after AF ablation (P ≤.0006). CONCLUSION: Cardiac miRs-21 and 150 are known to regulate genes implicated in atrial remodeling. Our findings show associations between plasma miRs-21 and 150 and AF, suggesting that circulating miRNAs can provide insights into cardiac gene regulation.


Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/cirurgia , Ablação por Cateter , MicroRNAs/sangue , Adulto , Idoso , Fibrilação Atrial/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Regulação da Expressão Gênica , Átrios do Coração/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Nat Commun ; 5: 3650, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24722188

RESUMO

Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases.


Assuntos
Transtorno Autístico/metabolismo , Processamento Alternativo/genética , Processamento Alternativo/fisiologia , Transtorno Autístico/genética , Predisposição Genética para Doença/genética , Humanos , Dados de Sequência Molecular , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/fisiologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fatores de Risco
13.
BMJ Open ; 4(1): e004097, 2014 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-24413351

RESUMO

INTRODUCTION: Emerging epidemiological data suggest that obstructive sleep apnoea (OSA) is common in the general surgical population. Unfortunately, the majority of these patients are unrecognised and untreated at the time of surgery. There is substantial biological rationale to indicate that patients with unrecognised OSA are at a higher risk of postoperative vascular events. However, the extent of this morbidity is currently unknown. We have initated the postoperative vascular complications in the unrecognised obstructive sleep apnoea (POSA) study to determine the associations between OSA, nocturnal hypoxia and major postoperative vascular events in 1200 moderate-to-high risk patients undergoing major non-cardiac surgery. METHODS AND ANALYSIS: The POSA study is an international prospective observational cohort study. Using a type 3 portable sleep monitoring device and ambulatory oximetry, we will quantify the severity of OSA. The primary outcome is a composite of vascular death, myocardial infarction; non-fatal cardiac arrest; stroke; pulmonary embolism; congestive heart failure and new arrhythmia within 30 days of surgery. As of November 2013, we have recruited over 700 patients from nine centres in six countries. The mean age is 68 years, the mean body mass index is 27 kg/m(2) and 55% of patients are men. 27.9% of patients have known coronary artery disease, over 76% have diabetes. The majority of patients underwent orthopaedic surgery (28%) and colorectal resection (18.5%). ETHICS AND DISSEMINATION: The POSA study has received ethics approval from all study sites before patient recruitment. Informed consent will be obtained from all patients. The POSA study will determine the risk of unrecognised OSA in major non-cardiac surgery. We will publish these findings in peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01494181.


Assuntos
Complicações Pós-Operatórias/etiologia , Apneia Obstrutiva do Sono/complicações , Procedimentos Cirúrgicos Operatórios , Doenças Vasculares/etiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Projetos de Pesquisa , Medição de Risco
14.
Age Ageing ; 43(1): 91-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23978408

RESUMO

BACKGROUND: home visits and telephone calls are two often used approaches in transitional care but their differential effects are unknown. OBJECTIVE: to examine the overall effects of a transitional care programme for discharged medical patients and the differential effects of telephone calls only. DESIGN: randomised controlled trial. SETTING: a regional hospital in Hong Kong. PARTICIPANTS: patients discharged from medical units fitting the inclusion criteria (n = 610) were randomly assigned to: control ('control', n = 210), home visits with calls ('home', n = 196) and calls only ('call', n = 204). INTERVENTION: the home groups received alternative home visits and calls and the call groups calls only for 4 weeks. The control group received two placebo calls. The nurse case manager was supported by nursing students in delivering the interventions. RESULTS: the home visit group (after 4 weeks 10.7%, after 12 weeks 21.4%) and the call group (11.8, 20.6%) had lower readmission rates than the control group (17.6, 25.7%). Significance differences were detected in intention-to-treat (ITT) analysis for the home and intervention group (home and call combined) at 4 weeks. In the per-protocol analysis (PPA) results, significant differences were found in all groups at 4 weeks. There was significant improvement in quality of life, self-efficacy and satisfaction in both ITT and PPA for the study groups. CONCLUSIONS: this study has found that bundled interventions involving both home visits and calls are more effective in reducing readmissions. Many of the transitional care programmes use all-qualified nurses, and this study reveals that a mixed skills model seems to bring about positive effects as well.


Assuntos
Continuidade da Assistência ao Paciente , Enfermagem Domiciliar , Visita Domiciliar , Pacotes de Assistência ao Paciente , Alta do Paciente , Telefone , Idoso , Idoso de 80 Anos ou mais , Feminino , Hong Kong , Hospitais Gerais , Humanos , Análise de Intenção de Tratamento , Masculino , Readmissão do Paciente , Satisfação do Paciente , Qualidade de Vida , Autoeficácia , Fatores de Tempo , Resultado do Tratamento
15.
BMC Health Serv Res ; 12: 479, 2012 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-23259498

RESUMO

BACKGROUND: Readmissions are costly and have implications for quality of care. Studies have been reported to support effects of transitional care programs in reducing hospital readmissions and enhancing clinical outcomes. However, there is a paucity of studies executing full economic evaluation to assess the cost-effectiveness of these transitional care programs. This study is therefore launched to fill this knowledge gap. METHODS: Cost-effectiveness analysis was conducted alongside a randomized controlled trial that examined the effects of a Health-Social Transitional Care Management Program (HSTCMP) for medical patients discharged from an acute regional hospital in Hong Kong. The cost and health outcomes were compared between the patients receiving the HSTCMP and usual care. The total costs comprised the pre-program, program, and healthcare utilization costs. Quality of life was measured with SF-36 and transformed to utility values between 0 and 1. RESULTS: The readmission rates within 28 (control 10.2%, study 4.0%) and 84 days (control 19.4%, study 8.1%) were significantly higher in the control group. Utility values showed no difference between the control and study groups at baseline (p = 0.308). Utility values for the study group were significantly higher than in the control group at 28 (p < 0.001) and 84 days (p = 0.002). The study group also had a significantly higher QALYs gain (p < 0.001) over time at 28 and 84 days when compared with the control group. The intervention had an 89% chance of being cost-effective at the threshold of £20000/QALY. CONCLUSIONS: Previous studies on transitional care focused mainly on clinical outcomes and not too many included cost as an outcome measure. Studies examining the cost-effectiveness of the post-discharge support services are scanty. This study is the first to examine the cost-effectiveness of a transitional care program that used nurse-led services participated by volunteers. Results have shown that a health-social partnership transitional care program is cost-effective in reducing healthcare costs and attaining QALY gains. Economic evaluation helps to inform funders and guide decisions for the effective use of competing healthcare resources.


Assuntos
Continuidade da Assistência ao Paciente , Alta do Paciente , Readmissão do Paciente , Intervalos de Confiança , Continuidade da Assistência ao Paciente/economia , Continuidade da Assistência ao Paciente/organização & administração , Análise Custo-Benefício/métodos , Hong Kong , Humanos , Readmissão do Paciente/economia , Readmissão do Paciente/tendências , Qualidade de Vida , Inquéritos e Questionários
16.
Microbes Infect ; 14(13): 1133-43, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22634423

RESUMO

The early host response during pulmonary nocardiosis is highly dependent on neutrophils and the successful clearance of bacteria in tissue. The data presented in this study showed that IL-17 mediated the neutrophil response following intranasal inoculation with Nocardia asteroides strain GUH-2. Flow cytometry revealed that neutrophil levels in C57BL/6 mice were increased by day 1 post inoculation and remained elevated until day 3, during which time the majority of bacterial clearance occurred. Intracellular cytokine staining for IL-17 showed a 3.5- to 5-fold increase in IL-17 producing T-lymphocytes that were predominately comprised by CD4(-)CD8(-) γδ T-lymphocytes. The importance of IL-17 and γδ T-cells was determined by the in vivo administration of antibody, capable of blocking IL-17 binding or TCR δ, respectively. Neutralization of either IL-17 or γδ T-cells in Nocardia treated mice resulted in attenuated neutrophil infiltration. Paralleling this impaired neutrophil recruitment, nearly a 10-fold increase in bacterial burden was observed in both anti-IL-17 and anti-TCR δ treated animals. Together, these data indicate a protective role for IL-17 and suggest that IL-17 producing γδ T-lymphocytes contribute to neutrophil infiltration during pulmonary nocardiosis.


Assuntos
Interleucina-17/imunologia , Neutrófilos/imunologia , Nocardiose/imunologia , Nocardia asteroides/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Feminino , Imunidade Inata , Interleucina-17/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos/imunologia , Neutrófilos/metabolismo , Nocardiose/microbiologia , Nocardia asteroides/crescimento & desenvolvimento , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/metabolismo
17.
Soc Sci Med ; 73(7): 960-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21839564

RESUMO

Hospital readmission is an indicator of care quality. Studies have been conducted to test whether post-discharge transitional care programs can reduce hospital readmission, but results are not conclusive. The contemporary development of post-discharge support advocates a health and social partnership approach. There is a paucity of experimental studies examining the effects of such efforts. This study designed a health-social transitional care management program (HSTCMP) and subjected it to empirical testing using a randomized controlled trial in the medical units of an acute general hospital with 1700 beds in Hong Kong during the period of February 2009 to July 2010. Results using per-protocol analysis revealed that the HSTCMP significantly reduced readmission at 4-weeks (study 4.0%, control 10.2%, χ(2) = 7.98, p = 0.005). The intention-to-treat result also showed a lower readmission rate with the study group but the result was not significant (study 11.5%, control 14.7%, χ(2) = 1.53, p = 0.258). There was however significant improvement in quality of life, self-efficacy and satisfaction in the study group in both per-protocol and intention-to-treat analyses. The study suggests that a health-social partnership, using volunteers as substitutes for some of the professional care, may be effective for general medical patients.


Assuntos
Redes Comunitárias , Continuidade da Assistência ao Paciente , Readmissão do Paciente/tendências , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Qualidade de Vida , Autoeficácia
18.
Science ; 333(6042): 596-601, 2011 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-21798943

RESUMO

Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.


Assuntos
Arabidopsis/imunologia , Arabidopsis/metabolismo , Interações Hospedeiro-Patógeno , Doenças das Plantas/imunologia , Imunidade Vegetal , Receptores Imunológicos/metabolismo , Fatores de Virulência/metabolismo , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Bactérias/metabolismo , Evolução Molecular , Genes de Plantas , Imunidade Inata , Oomicetos/patogenicidade , Mapeamento de Interação de Proteínas , Pseudomonas syringae/patogenicidade
19.
Nat Methods ; 8(6): 478-80, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21516116

RESUMO

Next-generation sequencing has not been applied to protein-protein interactome network mapping so far because the association between the members of each interacting pair would not be maintained in en masse sequencing. We describe a massively parallel interactome-mapping pipeline, Stitch-seq, that combines PCR stitching with next-generation sequencing and used it to generate a new human interactome dataset. Stitch-seq is applicable to various interaction assays and should help expand interactome network mapping.


Assuntos
Bases de Dados de Proteínas/estatística & dados numéricos , Mapeamento de Interação de Proteínas/estatística & dados numéricos , Análise de Sequência de DNA/estatística & dados numéricos , Humanos , Fases de Leitura Aberta , Reação em Cadeia da Polimerase , Técnicas do Sistema de Duplo-Híbrido
20.
Ann Thorac Surg ; 89(1): 283-5, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20103258

RESUMO

Partial anomalous pulmonary venous connection with infradiaphragmatic drainage into the inferior vena cava (scimitar syndrome) constitutes a rare diagnosis in adults. Diagnosis is suggested by plain chest roentgenogram and confirmed by computed tomography angiography or magnetic resonance imaging. Reported operations for scimitar syndrome are complex, often requiring circulatory arrest. Reoperation for pulmonary vein stenosis is a troubling complication. We report an effective simplified operation for use in adults.


Assuntos
Veias Pulmonares/anormalidades , Malformações Vasculares/diagnóstico , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Seguimentos , Humanos , Angiografia por Ressonância Magnética , Masculino , Radiografia Torácica , Malformações Vasculares/cirurgia
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