Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
BMC Health Serv Res ; 23(1): 231, 2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36890546

RESUMEN

BACKGROUND: While processes of adoption and the impacts of various health technologies have been extensively studied by health services and policy researchers, the influence of policy makers' governing styles on these processes have been largely neglected. Through a comparative analysis of non-invasive prenatal testing (NIPT) in the Canadian provinces of Ontario and Quebec, this article examines how decisions about this technology were shaped by contrasting political ideologies, resulting in vastly different innovation and adoption strategies and outcomes. METHODS: A comparative qualitative investigation comprising of a document analysis followed by semi-structured interviews with key informants. Interview participants were researchers, clinicians, and private sector medical laboratory employees based in Ontario and Quebec, Canada. Interviews were conducted both in person and virtually- owing partly to the COVID-19 pandemic - to garner perspectives regarding the adoption and innovation processes surrounding non-invasive prenatal testing in both provinces. All interviews were recorded and transcribed verbatim and data were analyzed using thematic analysis. RESULTS: Through an analysis of 21 in-depth interview transcripts and key documents, the research team identified three central themes: 1) health officials in each province demonstrated a unique approach to using the existing scholarly literature on NIPT; 2) each provincial government demonstrated its own preference for service delivery, with Ontario preferring private and Quebec preferring public; and finally, 3) both Ontario and Quebec's strategies to NIPT adoption and innovation was contextualized within each province's unique financial positioning and concerns. These findings illustrate how both Quebec's nationalist focus and use of industrial policy and Ontario's 'New Public Management' style had implications for how this emerging healthcare technology was made available within each province's publicly-financed health system. CONCLUSIONS: Our study reveals how these governments' differing approaches to using data and research, public versus private service delivery, and financial goals and concerns resulted in distinct testing technologies, access, and timelines for NIPT adoption. Our analysis demonstrates the need for health policy researchers, policy makers, and others to move beyond analyses solely considering clinical and health economic evidence to understand the impact of political ideologies and governing styles.


Asunto(s)
COVID-19 , Pandemias , Embarazo , Femenino , Humanos , Ontario , Quebec , Investigación Cualitativa , COVID-19/diagnóstico , COVID-19/epidemiología , Política de Salud , Tecnología Biomédica
2.
BMC Health Serv Res ; 22(1): 92, 2022 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35057805

RESUMEN

BACKGROUND: Choosing Wisely (CW) is an international movement comprised of campaigns in more than 20 countries to reduce low-value care (LVC). De-implementation, the reduction or removal of a healthcare practice that offers little to no benefit or causes harm, is an emerging field of research. Little is known about the factors which (i) sustain LVC; and (ii) the magnitude of the problem of LVC. In addition, little is known about the processes of de-implementation, and if and how these processes differ from implementation endeavours. The objective of this study was to explicate the myriad factors which impact the processes and outcomes of de-implementation initiatives that are designed to address national Choosing Wisely campaign recommendations. METHODS: Semi-structured interviews were conducted with individuals implementing Choosing Wisely Canada recommendations in healthcare settings in four provinces. The interview guide was developed using concepts from the literature and the Implementation Process Model (IPM) as a framework. All interviews were conducted virtually, recorded, and transcribed verbatim. Data were analysed using thematic analysis. FINDINGS: Seventeen Choosing Wisely team members were interviewed. Participants identified numerous provider factors, most notably habit, which sustain LVC. Contrary to reporting in recent studies, the majority of LVC in the sample was not 'patient facing'; therefore, patients were not a significant driver for the LVC, nor a barrier to reducing it. Participants detailed aspects of the magnitude of the problems of LVC, providing insight into the complexities and nuances of harm, resources and prevalence. Harm from potential or common infections, reactions, or overtreatment was viewed as the most significant types of harm. Unique factors influencing the processes of de-implementation reported were: influence of Choosing Wisely campaigns, availability of data, lack of targets and hard-coded interventions. CONCLUSIONS: This study explicates factors ranging from those which impact the maintenance of LVC to factors that impact the success of de-implementation interventions intended to reduce them. The findings draw attention to the significance of unintentional factors, highlight the importance of understanding the impact of harm and resources to reduce LVC and illuminate the overstated impact of patients in de-implementation literature. These findings illustrate the complexities of de-implementation.


Asunto(s)
Atención de Bajo Valor , Sobretratamiento , Canadá , Hospitales , Humanos , Investigación Cualitativa
3.
Healthc Q ; 25(1): 49-56, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35596765

RESUMEN

The healthcare system is complex and requires effective leaders who can navigate team, organizational and system dynamics. The objectives of this study were to explore competencies required to lead emerging healthcare challenges and identify strategies for developing successful leaders. Semi-structured interviews were conducted with 12 healthcare leaders from the government, hospitals and in consulting. This study unpacks competencies such as communication and change management and draws attention to the significance of emotional intelligence and working with data that have not traditionally been identified as key competencies. These findings can inform curriculum and modernization initiatives in healthcare leadership programs.


Asunto(s)
Curriculum , Liderazgo , Atención a la Salud , Humanos
4.
N Engl J Med ; 389(22): 2111-2, 2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-38048202

Asunto(s)
Asma , Adulto , Humanos
5.
BMC Health Serv Res ; 21(1): 558, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098952

RESUMEN

BACKGROUND: There is general scarcity of research on key elements of implementation processes and the factors which impact implementation success. Implementation of healthcare interventions is a complex process. Tools to support implementation can facilitate this process and improve effectiveness of the interventions and clinical outcomes. Understanding the impact of implementation support tools is a critical aspect of this process. The objective of this study was to solicit knowledge and agreement from relevant implementation science and knowledge translation healthcare experts in order to develop a process model of key elements in the implementation process. METHODS: A two round, modified Delphi study involving international experts in knowledge translation and implementation (researchers, scientists, professors, decision-makers) was conducted. Participants rated and commented on all aspects of the process model, including the organization, content, scope, and structure. Delphi questions rated at 75% agreement or lower were reviewed and revised. Qualitative comments supported the restructuring and refinement. A second-round survey followed the same process as Round 1. RESULTS: Fifty-four experts participated in Round 1, and 32 experts participated in Round 2. Twelve percent (n = 6) of the Round 1 questions did not reach agreement. Key themes for revision and refinement were: stakeholder engagement throughout the process, iterative nature of the implementation process; importance of context; and importance of using guiding theories or frameworks. The process model was revised and refined based on the quantitative and qualitative data and reassessed by the experts in Round 2. Agreement was achieved on all items in Round 2 and the Delphi concluded. Additional feedback was obtained regarding terminology, target users and definition of the implementation process. CONCLUSIONS: High levels of agreement were attained for all sub-domains, elements, and sub-elements of the Implementation Process Model. This model will be used to develop an Implementation Support Tool to be used by healthcare providers to facilitate effective implementation and improved clinical outcomes.


Asunto(s)
Atención a la Salud , Personal de Salud , Técnica Delphi , Humanos , Encuestas y Cuestionarios , Investigación Biomédica Traslacional
6.
PLoS Biol ; 15(8): e2001992, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28771465

RESUMEN

Mature human B cells infected by Epstein-Barr virus (EBV) become activated, grow, and proliferate. If the cells are infected ex vivo, they are transformed into continuously proliferating lymphoblastoid cell lines (LCLs) that carry EBV DNA as extra-chromosomal episomes, express 9 latency-associated EBV proteins, and phenotypically resemble antigen-activated B-blasts. In vivo similar B-blasts can differentiate to become memory B cells (MBC), in which EBV persistence is established. Three related latency-associated viral proteins EBNA3A, EBNA3B, and EBNA3C are transcription factors that regulate a multitude of cellular genes. EBNA3B is not necessary to establish LCLs, but EBNA3A and EBNA3C are required to sustain proliferation, in part, by repressing the expression of tumour suppressor genes. Here we show, using EBV-recombinants in which both EBNA3A and EBNA3C can be conditionally inactivated or using virus completely lacking the EBNA3 gene locus, that-after a phase of rapid proliferation-infected primary B cells express elevated levels of factors associated with plasma cell (PC) differentiation. These include the cyclin-dependent kinase inhibitor (CDKI) p18INK4c, the master transcriptional regulator of PC differentiation B lymphocyte-induced maturation protein-1 (BLIMP-1), and the cell surface antigens CD38 and CD138/Syndecan-1. Chromatin immunoprecipitation sequencing (ChIP-seq) and chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) indicate that in LCLs inhibition of CDKN2C (p18INK4c) and PRDM1 (BLIMP-1) transcription results from direct binding of EBNA3A and EBNA3C to regulatory elements at these loci, producing stable reprogramming. Consistent with the binding of EBNA3A and/or EBNA3C leading to irreversible epigenetic changes, cells become committed to a B-blast fate <12 days post-infection and are unable to de-repress p18INK4c or BLIMP-1-in either newly infected cells or conditional LCLs-by inactivating EBNA3A and EBNA3C. In vitro, about 20 days after infection with EBV lacking functional EBNA3A and EBNA3C, cells develop a PC-like phenotype. Together, these data suggest that EBNA3A and EBNA3C have evolved to prevent differentiation to PCs after infection by EBV, thus favouring long-term latency in MBC and asymptomatic persistence.


Asunto(s)
Linfocitos B/virología , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/fisiología , Proteínas Virales/fisiología , Latencia del Virus , Linfocitos B/fisiología , Biomarcadores/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/metabolismo , Código de Histonas , Humanos , Inmunoglobulinas/metabolismo , Células Plasmáticas/metabolismo , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Proteínas Represoras/metabolismo
7.
J Virol ; 92(21)2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30135119

RESUMEN

Epstein-Barr virus nuclear antigen 3C (EBNA3C) is a well-defined repressor of host gene expression in B cells transformed by Epstein-Barr virus (EBV) that cooperates with various cellular factors. It is established that EBNA3C interacts with the cellular factor RBPJ (RBP-Jκ or CBF1) through two distinct motifs: the TFGC motif, also called the homology domain (HD) motif, and the VWTP motif. In this study, we investigated the role of each motif in EBNA3C transcriptional repression activity by using two novel recombinant viruses with single RBPJ interaction motifs mutated (EBNA3C HDmut and EBNA3C W227S). Infection of primary B cells with either of these recombinant EBVs led to the successful establishment of lymphoblastoid cell lines (LCLs). Gene expression analysis showed that full repression of EBNA3C target genes is not achieved by EBNA3C HDmut compared to that with EBNA3C W227S or the EBNA3C wild type (WT). Focusing on the well-characterized EBNA3C-repressed genes COBLL1, ADAM28, and ADAMDEC1, we investigated the mechanism of EBNA3C-mediated transcriptional repression. Chromatin immunoprecipitation (ChIP) analysis indicated that EBNA3C HDmut is still able to recruit Polycomb proteins BMI1 and SUZ12 to COBLL1 as efficiently as EBNA3C WT does, leading to the full deposition of the repressive histone mark H3K27me3. However, we found that the activation-associated chromatin mark H3K4me3 is highly enriched at EBNA3C target genes in LCLs expressing EBNA3C HDmut. We show here that EBNA3C interacts with the histone lysine demethylase KDM2B and that this interaction is important for H3K4me3 removal and for the EBNA3C-mediated repression of COBLL1 and the ADAM28-ADAMDEC1 locus.IMPORTANCE EBV is a virus associated with human cancers and is well known for its ability to transform B lymphocytes into continuously proliferating lymphoblastoid cell lines. EBNA3C is considered an oncoprotein and has been shown to be essential for B cell transformation by EBV. EBNA3C is well characterized as a viral transcription factor, but very little is known about its mechanisms of action. In the present study, we demonstrate that removal of the activating histone mark H3K4me3 and deposition of the repressive mark H3K27me3 by EBNA3C on COBLL1 are achieved by at least two distinct mechanisms. Furthermore, we discovered that EBNA3C interacts with the lysine demethylase KDM2B and that this interaction is important for its transcriptional repressive function. The findings in this study provide new insights into the mechanism used by the oncoprotein EBNA3C to repress cellular target genes.


Asunto(s)
Proteínas ADAM/biosíntesis , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Proteínas F-Box/metabolismo , Histonas/metabolismo , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Factores de Transcripción/biosíntesis , Linfocitos B/metabolismo , Células Cultivadas , Inmunoprecipitación de Cromatina , Antígenos Nucleares del Virus de Epstein-Barr/genética , Expresión Génica/fisiología , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/genética , Proteínas de Neoplasias , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 2/metabolismo
8.
Int Urogynecol J ; 30(5): 705-710, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30306193

RESUMEN

INTRODUCTION AND HYPOTHESIS: To identify the association between the symptom severity and outcome of conservative management for OAB, SUI and MUI. Conservative treatments are recommended for overactive bladder (OAB), stress urinary incontinence (SUI) and mixed incontinence (MUI). It is unclear whether disease severity affects treatment outcome. METHODS: Patients receiving conservative management were reviewed. Disease-specific questionnaires (OAB-q SF, ICIQ-UI SF) and bladder diaries recorded baseline symptoms. Success was defined by Patient Global Impression of Improvement questionnaire (PGI-I) response of "very much better" or "much better". Non-parametric statistical tests and logistic regression were used. RESULTS: In 50 OAB patients success was associated with lower symptom severity [30 (0-80) vs. 80 (23-100), p = 0.0001], fewer urgency episodes [4 (0-12) vs. 6 (0-11), p = 0.032] and lower ICIQ-UI SF [5.5 (0-20) vs. 15 (0-21), p = 0.002], but higher QoL [67 (20-101) vs. 24 (6-58), p = 0.0001]. In 50 MUI patients, variables were fewer urgency episodes [3 (0-10) vs. 6 (0-16), p = 0.004] and lower ICIQ-UI [11 (1-18) vs. 15 (5-21), p = 0.03]. In 40 SUI patients, variables were fewer incontinence episodes [1 (0-4) vs. 2 (0-5), p = 0.05] and lower ICIQ-UI [11 (6-16) vs. 13.5 (11-19), p = 0.003]. Multiple regression confirmed OAB-q QoL [odds ratio (OR) 1.10 (95% confidence intervals 1.04, 1.1)] for OAB, urgency episodes [OR 0.74 (0.56, 0.98)] and ICIQ-UI [OR 0.83 (0.71, 0.98] for MUI and ICIQ-UI [OR 0.57 (0.40, 0.83)] for SUI. CONCLUSIONS: Milder baseline disease severity was associated with successful outcome. There is potential for triage at initial assessment to second-line interventions for women unlikely to achieve success.


Asunto(s)
Tratamiento Conservador/métodos , Índice de Severidad de la Enfermedad , Vejiga Urinaria Hiperactiva/terapia , Incontinencia Urinaria de Esfuerzo/terapia , Incontinencia Urinaria de Urgencia/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento
9.
Nucleic Acids Res ; 45(5): 2368-2383, 2017 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-27903901

RESUMEN

ChIP-seq performed on lymphoblastoid cell lines (LCLs), expressing epitope-tagged EBNA3A, EBNA3B or EBNA3C from EBV-recombinants, revealed important principles of EBNA3 binding to chromatin. When combined with global chromatin looping data, EBNA3-bound loci were found to have a singular character, each directly associating with either EBNA3-repressed or EBNA3-activated genes, but not with both. EBNA3A and EBNA3C showed significant association with repressed and activated genes. Significant direct association for EBNA3B loci could only be shown with EBNA3B-repressed genes. A comparison of EBNA3 binding sites with known transcription factor binding sites in LCL GM12878 revealed substantial co-localization of EBNA3s with RUNX3-a protein induced by EBV during B cell transformation. The beta-subunit of core binding factor (CBFß), that heterodimerizes with RUNX3, could co-immunoprecipitate robustly EBNA3B and EBNA3C, but only weakly EBNA3A. Depletion of either RUNX3 or CBFß with lentivirus-delivered shRNA impaired epitope-tagged EBNA3B and EBNA3C binding at multiple regulated gene loci, indicating a requirement for CBF heterodimers in EBNA3 recruitment during target-gene regulation. ShRNA-mediated depletion of CBFß in an EBNA3C-conditional LCL confirmed the role of CBF in the regulation of EBNA3C-induced and -repressed genes. These results reveal an important role for RUNX3/CBF during B cell transformation and EBV latency that was hitherto unexplored.


Asunto(s)
Factores de Unión al Sitio Principal/metabolismo , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Regulación de la Expresión Génica , Sitios de Unión , Línea Celular , Cromatina/química , Cromatina/metabolismo , Inmunoprecipitación de Cromatina , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 3 del Factor de Unión al Sitio Principal/fisiología , Subunidad beta del Factor de Unión al Sitio Principal/metabolismo , Factores de Unión al Sitio Principal/fisiología , Elementos de Facilitación Genéticos , Genoma Humano , Humanos , Factores de Transcripción/metabolismo , Sitio de Iniciación de la Transcripción
10.
PLoS Pathog ; 11(7): e1005031, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26153983

RESUMEN

We show that two host-encoded primary RNAs (pri-miRs) and the corresponding microRNA (miR) clusters--widely reported to have cell transformation-associated activity--are regulated by EBNA3A and EBNA3C. Utilising a variety of EBV-transformed lymphoblastoid cell lines (LCLs) carrying knockout-, revertant- or conditional-EBV recombinants, it was possible to demonstrate unambiguously that EBNA3A and EBNA3C are both required for transactivation of the oncogenic miR-221/miR-222 cluster that is expressed at high levels in multiple human tumours--including lymphoma/leukemia. ChIP, ChIP-seq, and chromosome conformation capture analyses indicate that this activation results from direct targeting of both EBV proteins to chromatin at the miR-221/miR-222 genomic locus and activation via a long-range interaction between enhancer elements and the transcription start site of a long non-coding pri-miR located 28 kb upstream of the miR sequences. Reduced levels of miR-221/miR-222 produced by inactivation or deletion of EBNA3A or EBNA3C resulted in increased expression of the cyclin-dependent kinase inhibitor p57KIP2, a well-established target of miR-221/miR-222. MiR blocking experiments confirmed that miR-221/miR-222 target p57KIP2 expression in LCLs. In contrast, EBNA3A and EBNA3C are necessary to silence the tumour suppressor cluster miR-143/miR-145, but here ChIP-seq suggests that repression is probably indirect. This miR cluster is frequently down-regulated or deleted in human cancer, however, the targets in B cells are unknown. Together these data indicate that EBNA3A and EBNA3C contribute to B cell transformation by inhibiting multiple tumour suppressor proteins, not only by direct repression of protein-encoding genes, but also by the manipulation of host long non-coding pri-miRs and miRs.


Asunto(s)
Transformación Celular Neoplásica/genética , Antígenos Nucleares del Virus de Epstein-Barr/genética , MicroARNs/genética , Linfocitos B/virología , Western Blotting , Inmunoprecipitación de Cromatina , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/biosíntesis , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Inmunoprecipitación , MicroARNs/biosíntesis , Oncogenes , Reacción en Cadena en Tiempo Real de la Polimerasa
11.
BMC Health Serv Res ; 16(a): 375, 2016 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-27514660

RESUMEN

BACKGROUND: Reablement is a time-limited intervention that aims to support people to regain independence and enable them to resume their daily activities after they return home from an in-patient care setting, or to maintain independence to enable them to remain at home. There is some evidence that reablement can enhance independence and has the potential to contain costs. However, reablement services are funded and provided in different ways and by different organisations, and there is limited research evidence about the effectiveness of different reablement service models. This study will evaluate the effectiveness and cost-effectiveness of different reablement service models and service users' and carers' experiences of reablement in England, UK. METHODS/DESIGN: The study will use a quasi-experimental mixed methods design that comprises three work packages (WP) extending over a period of 34 months. WP1 will conduct cluster analysis on survey data to develop a typology of current models of reablement services in order to describe the current reablement service landscape. WP2 will comprise a quantitative outcomes evaluation of the effectiveness of the different service models; a process evaluation and an economic evaluation. WP2 will be set within generic reablement services, where providers are using the most commonly employed generic reablement service types identified in WP1; the primary outcome measure is health-related quality of life measured by the EQ-5D-5L. WP3 will provide evidence about specialist reablement services and how specialist approaches and practices are organised and delivered. DISCUSSION: Managing demands on care services is, and will remain, a crucial factor for the UK National Health Service as the number of people with long-term conditions rise. There has been, and will continue to be, significant investment in reablement services. The proposed study will address several key areas where there is limited evidence regarding the organisation and delivery of reablement services in England, UK. Specifically, it will provide new evidence on different models of reablement services that will be of direct benefit to health and social care managers, commissioners and their partner organisations.


Asunto(s)
Programas de Gobierno/organización & administración , Servicios de Atención de Salud a Domicilio/organización & administración , Análisis por Conglomerados , Análisis Costo-Beneficio , Inglaterra/epidemiología , Encuestas de Atención de la Salud , Necesidades y Demandas de Servicios de Salud , Humanos , Vida Independiente , Calidad de Vida
12.
PLoS Pathog ; 9(2): e1003187, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23436997

RESUMEN

To explore the role of p16(INK4a) as an intrinsic barrier to B cell transformation by EBV, we transformed primary B cells from an individual homozygous for a deletion in the CDKN2A locus encoding p16(INK4a) and p14(ARF). Using recombinant EBV-BAC viruses expressing conditional EBNA3C (3CHT), we developed a system that allows inactivation of EBNA3C in lymphoblastoid cell lines (LCLs) lacking active p16(INK4a) protein but expressing a functional 14(ARF)-fusion protein (p14/p16). The INK4a locus is epigenetically repressed by EBNA3C--in cooperation with EBNA3A--despite the absence of functional p16(INK4a). Although inactivation of EBNA3C in LCLs from normal B cells leads to an increase in p16(INK4a) and growth arrest, EBNA3C inactivation in the p16(INK4a)-null LCLs has no impact on the rate of proliferation, establishing that the repression of INK4a is a major function of EBNA3C in EBV-driven LCL proliferation. This conditional LCL system allowed us to use microarray analysis to identify and confirm genes regulated specifically by EBNA3C, independently of proliferation changes modulated by the p16(INK4a)-Rb-E2F axis. Infections of normal primary B cells with recombinant EBV-BAC virus from which EBNA3C is deleted or with 3CHT EBV in the absence of activating ligand 4-hydroxytamoxifen, revealed that EBNA3C is necessary to overcome an EBV-driven increase in p16(INK4a) expression and concomitant block to proliferation 2-4 weeks post-infection. If cells are p16(INK4a)-null, functional EBNA3C is dispensable for the outgrowth of LCLs.


Asunto(s)
Linfocitos B/virología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Represión Epigenética/genética , Herpesvirus Humano 4/fisiología , Activación de Linfocitos , Antígenos Virales/genética , Antígenos Virales/metabolismo , Línea Celular , Proliferación Celular , Supervivencia Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Antígenos Nucleares del Virus de Epstein-Barr/genética , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Sitios Genéticos , Herpesvirus Humano 4/inmunología , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación , Cultivo Primario de Células , Latencia del Virus
13.
Clin Orthop Relat Res ; 473(2): 615-22, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25287520

RESUMEN

BACKGROUND: The Bernese periacetabular osteotomy (PAO) has entered its fourth decade and is frequently used for corrective osteotomy in patients with acetabular dysplasia. Although our capacity to preserve the joint after corrective osteotomy is excellent, gaining a better understanding on how well patients function after this surgery is important as well. QUESTIONS/PURPOSES: (1) What changes in patient-reported outcomes scores occur in patients treated with PAO for hip dysplasia in the setting of a single-surgeon practice? (2) What are the predictors of clinical function and survivorship? METHODS: All 67 patients presenting to a single surgeon's clinic with hip dysplasia treated with PAO between October 2005 and January 2013 were prospectively followed. Baseline demographic data as well as pre- and postoperative radiographic and functional measurements were obtained with a minimum of 1-year followup. Radiographic criteria included Tönnis grade, Tönnis angle, minimum joint space width, center-edge angle, presence of crossover sign, medial translation of the hip center, and alpha angle. We also used validated outcome measures including the WOMAC, the UCLA Activity Scale, and the SF-12. Multiple regression analysis was used to determine predictors of functional outcome scores. RESULTS: There were increases in WOMAC, UCLA, and SF-12 Physical scores. Higher preoperative alpha angle was associated with a lower postoperative WOMAC score (ß=-0.47; 95% confidence interval [CI], -0.92 to -0.02; R2=0.08; p=0.04). The 5-year Kaplan-Meier survivorship was 94.1% (95% CI, 90.7-97.5) with reoperation (ie, hip arthroscopy and/or total hip arthroplasty) used as the endpoint for failure. With the limited numbers available, we could not identify any demographic or radiographic factors associated with reoperation. CONCLUSIONS: Overall survivorship for the PAO at our center at 5 years is comparable to other clinical series with overall functional scores improving. A greater alpha angle preoperatively was associated with poorer patient-reported outcome scores. Further research is needed to determine how and when intraarticular cartilage damage associated with dysplasia needs to be addressed. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Asunto(s)
Luxación de la Cadera/cirugía , Osteotomía/métodos , Evaluación de Resultado en la Atención de Salud , Acetábulo/cirugía , Adulto , Femenino , Luxación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/cirugía , Humanos , Masculino , Radiografía , Reoperación , Adulto Joven
14.
J Arthroplasty ; 30(9): 1502-5, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25913231

RESUMEN

The purpose of this study was to report the clinical results of surgical dislocation of the hip in the treatment of pre-arthritic hip disease. Between 2005 and 2010, eighty-two patients (89 hips) underwent a surgical dislocation of the hip at a mean age of 30.5 years (range 14.8-51.7); 10 females and 72 males. At a mean follow-up of 7.1 years (range 5-9.6) clinical function improved significantly. 6 patients were converted to total hip arthroplasty and 3 patients underwent an arthroscopy and an additional three patients had >1mm of joint space narrowing at latest follow-up giving us a 9-year cumulative Kaplan-Meier survivorship of 86.4% (CI, 79% to 94%). Thirty-four patients underwent internal fixation removal at a mean of 12.0 months (range 0.3-40.8 months). Although effective in the treatment of early hip disease, the surgical dislocation approach carries a high re-operation rate for removal of internal fixation; consequently, less invasive approaches should be considered for less complex deformities.


Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Cadera/cirugía , Luxaciones Articulares/cirugía , Adolescente , Adulto , Artroscopía , Remoción de Dispositivos , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/métodos , Articulación de la Cadera/cirugía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Reoperación , Adulto Joven
15.
Nucleic Acids Res ; 40(15): 7233-46, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22584624

RESUMEN

Detailed analyses of the chromatin around the BIM promoter has revealed that latent Epstein-Barr virus (EBV) triggers the recruitment of polycomb repressive complex 2 (PRC2) core subunits and the trimethylation of histone H3 lysine 27 (H3K27me3) at this locus. The recruitment is absolutely dependent on nuclear proteins EBNA3A and EBNA3C; what is more, epitope-tagged EBNA3C could be shown bound near the transcription start site (TSS). EBV induces no consistent changes in the steady-state expression of PRC2 components, but lentivirus delivery of shRNAs against PRC2 and PRC1 subunits disrupted EBV repression of BIM. The activation mark H3K4me3 is largely unaltered at this locus irrespective of H3K27me3 status, suggesting the establishment of a 'bivalent' chromatin domain. Consistent with the 'poised' nature of these domains, RNA polymerase II (Pol II) occupancy was not altered by EBV at the BIM TSS, but analysis of phospho-serine 5 on Pol II indicated that EBNA3A and EBNA3C together inhibit initiation of BIM transcripts. B cell lines carrying EBV encoding a conditional EBNA3C-oestrogen receptor-fusion revealed that this epigenetic repression of BIM was reversible, but took more than 3 weeks from when EBNA3C was inactivated.


Asunto(s)
Antígenos Virales/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Herpesvirus Humano 4/fisiología , Proteínas de la Membrana/genética , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/metabolismo , Proteína 11 Similar a Bcl2 , Línea Celular , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Histonas/metabolismo , Humanos , Histona Demetilasas con Dominio de Jumonji/metabolismo , Proteínas del Grupo Polycomb , Subunidades de Proteína/antagonistas & inhibidores , Subunidades de Proteína/metabolismo , ARN Polimerasa II/metabolismo , Proteínas Represoras/antagonistas & inhibidores , Transcripción Genética
16.
J Ment Health ; 23(3): 146-55, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24803221

RESUMEN

BACKGROUND: Personal budgets are a key policy priority in adult social care in England and are expected to become increasingly important in the care of adults with mental health problems. AIMS: This article systematically reviews evidence for the effectiveness of personal budgets for people with mental health problems across diverse outcomes. METHODS: The review, conducted in 2013, used the EPPI-Centre methodology for conducting a systematic review informed by Social Care Institute for Excellence guidelines. Data were extracted from studies and combined using meta-synthesis. RESULTS: Fifteen studies were included in the review which found mostly positive outcomes in terms of choice and control, quality of life, service use and cost-effectiveness. However, methodological limitations make these findings rather unreliable and insufficient to inform personal budgets policy and practice for mental health service users. CONCLUSIONS: Further high quality studies are required to inform policy and practice for mental health service users, which lags behind other adult social care groups in the use of personal budgets.


Asunto(s)
Presupuestos , Trastornos Mentales/psicología , Enfermos Mentales/psicología , Adulto , Femenino , Humanos , Masculino , Calidad de Vida
17.
BMC Med Educ ; 13: 140, 2013 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-24119470

RESUMEN

BACKGROUND: The demand for health professionals continues to increase, partially due to the aging population and the high proportion of practitioners nearing retirement. The University of British Columbia (UBC) has developed a program to address this demand, by providing support for internationally trained Physiotherapists in their preparation for taking the National Physiotherapy competency examinations.The aim was to create a program comprised of the educational tools and infrastructure to support internationally educated physiotherapists (IEPs) in their preparation for entry to practice in Canada and, to improve their pass rate on the national competency examination. METHODS: The program was developed using a logic model and evaluated using program evaluation methodology. Program tools and resources included educational modules and curricular packages which were developed and refined based on feedback from clinical experts, IEPs and clinical physical therapy mentors. An examination bank was created and used to include test-enhanced education. Clinical mentors were recruited and trained to provide clinical and cultural support for participants. RESULTS: The IEP program has recruited 124 IEPs, with 69 now integrated into the Canadian physiotherapy workforce, and more IEPs continuing to apply to the program. International graduates who participated in the program had an improved pass rate on the national Physiotherapy Competency Examination (PCE); participation in the program resulted in them having a 28% (95% CI, 2% to 59%) greater possibility of passing the written section than their counterparts who did not take the program. In 2010, 81% of all IEP candidates who completed the UBC program passed the written component, and 82% passed the clinical component. CONCLUSION: The program has proven to be successful and sustainable. This program model could be replicated to support the successful integration of other international health professionals into the workforce.


Asunto(s)
Médicos Graduados Extranjeros , Fisioterapeutas/educación , Colombia Británica , Competencia Clínica/normas , Curriculum , Evaluación Educacional , Humanos , Licencia Médica/normas , Mentores , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud
18.
PLoS One ; 18(4): e0285122, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37104298

RESUMEN

BACKGROUND: Decision impact studies have become increasingly prevalent in genomic medicine, particularly in cancer research. Such studies are designed to provide evidence of clinical utility for genomic tests by evaluating their impact on clinical decision-making. This paper offers insights into understanding of the origins and intentions of these studies through an analysis of the actors and institutions responsible for the production of this new type of evidence. METHODS: We conducted bibliometric and funding analyses of decision impact studies in genomic medicine research. We searched databases from inception to June 2022. The datasets used were primarily from Web of Science. Biblioshiny, additional R-based applications, and Microsoft Excel were used for publication, co-authorship and co-word analyses. RESULTS: 163 publications were included for the bibliometric analysis; a subset of 125 studies were included for the funding analysis. Included publications started in 2010 and increased steadily over time. Decision impact studies were primarily produced for proprietary genomic assays for use in cancer care. The author and affiliate analyses reveal that these studies were produced by 'invisible colleges' of researchers and industry actors with collaborations focused on producing evidence for proprietary assays. Most authors had an industry affiliation, and the majority of studies were funded by industry. While studies were conducted in 22 countries, the majority had at least one author from the USA. DISCUSSION: This study is a critical step in understanding the role of industry in the production of new types of research. Based on the data collected, we conclude that decision impact studies are industry-conceived and -produced evidence. The findings of this study demonstrate the depth of industry involvement and highlight a need for further research into the use of these studies in decision-making for coverage and reimbursement.


Asunto(s)
Investigación Biomédica , Medicina Genómica , Bibliometría , Industrias
19.
PLoS One ; 18(3): e0280582, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36897859

RESUMEN

BACKGROUND: Decision impact studies have become increasingly prevalent in cancer prognostic research in recent years. These studies aim to evaluate the impact of a genomic test on decision-making and appear to be a new form of evidence of clinical utility. The objectives of this review were to identify and characterize decision impact studies in genomic medicine in cancer care and categorize the types of clinical utility outcomes reported. METHODS: We conducted a search of four databases, Medline, Embase, Scopus and Web of Science, from inception to June 2022. Empirical studies that reported a "decision impact" assessment of a genomic assay on treatment decisions or recommendations for cancer patients were included. We followed scoping review methodology and adapted the Fryback and Thornbury Model to collect and analyze data on clinical utility. The database searches identified 1803 unique articles for title/abstract screening; 269 articles moved to full-text review. RESULTS: 87 studies met inclusion criteria. All studies were published in the last 12 years with the majority for breast cancer (72%); followed by other cancers (28%) (lung, prostate, colon). Studies reported on the impact of 19 different proprietary (18) and generic (1) assays. Across all four levels of clinical utility, outcomes were reported for 22 discrete measures, including the impact on provider/team decision-making (100%), provider confidence (31%); change in treatment received (46%); patient psychological impacts (17%); and costing or savings impacts (21%). Based on the data synthesis, we created a comprehensive table of outcomes reported for clinical utility. CONCLUSIONS: This scoping review is a first step in understanding the evolution and uses of decision impact studies and their influence on the integration of emerging genomic technologies in cancer care. The results imply that DIS are positioned to provide evidence of clinical utility and impact clinical practice and reimbursement decision-making in cancer care. Systematic review registration: Open Science Framework osf.io/hm3jr.


Asunto(s)
Neoplasias de la Mama , Masculino , Humanos , Pronóstico , Próstata , Genómica
20.
Clin Orthop Relat Res ; 470(12): 3361-7, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23001504

RESUMEN

BACKGROUND: Substantial acetabular cartilage damage is commonly present in patients suffering from femoral acetabular impingement (FAI). A better understanding of which patient is at risk of developing substantial cartilage damage is critical for establishing appropriate treatment guidelines. QUESTIONS/PURPOSES: We asked: (1) Does the cam deformity severity in FAI as assessed by alpha angle predict acetabular cartilage delamination? And (2) what are the clinical and radiographic findings in patients with acetabular cartilage delamination? METHODS: One hundred sixty-seven patients (129 males, 38 females) with a mean age of 38 years (range, 17-59 years) underwent joint preservation surgery for cam-type FAI. All data were collected prospectively. We assessed center-edge angle and Tönnis grade on AP radiographs and alpha angle on specialized lateral radiographs. Acetabular cartilage damage was assessed intraoperatively using the classification of Beck et al., with Type 3 and greater qualifying as delamination. RESULTS: For all hips, mean alpha angle was 65.5° (range, 41°-90°), and mean center-edge angle was 33.3° (range, 21°-52.5°). Patients with an alpha angle of 65° or greater had an odds ratio (OR) of 4.00 (95% CI, 1.26-12.71) of having Type 3 or greater damage. Increased age (OR, 1.04; 95% CI, 1.01-1.07) and male sex (OR, 2.24; 95% CI, 1.09-4.62) were associated with Type 3 or greater damage, while this was the opposite for acetabular coverage as assessed by center-edge angle (OR, 0.94; 95% CI, 0.89-0.99). CONCLUSIONS: Patients with cam-type FAI and an alpha angle of 65° or more are at increased risk of substantial cartilage damage while increasing acetabular coverage appears to have a protective effect. LEVEL OF EVIDENCE: Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Acetábulo/diagnóstico por imagen , Cartílago Articular/diagnóstico por imagen , Pinzamiento Femoroacetabular/diagnóstico por imagen , Acetábulo/cirugía , Adolescente , Adulto , Cartílago Articular/cirugía , Progresión de la Enfermedad , Femenino , Pinzamiento Femoroacetabular/complicaciones , Pinzamiento Femoroacetabular/cirugía , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Osteoartritis de la Cadera/diagnóstico por imagen , Osteoartritis de la Cadera/etiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Radiografía , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA