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1.
Nucleic Acids Res ; 51(22): 12092-12110, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37889078

RESUMO

Epstein-Barr virus (EBV) establishes lifelong asymptomatic infection by replication of its chromatinized episomes with the host genome. EBV exhibits different latency-associated transcriptional repertoires, each with distinct three-dimensional structures. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents 1.3-30.9% of all gastric cancers globally. EBV-positive gastric cancers exhibit an intermediate viral transcription profile known as 'Latency II', expressing specific viral genes and noncoding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II and III latencies exhibit different 3D structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV genome at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Infecções por Vírus Epstein-Barr/virologia , Expressão Gênica , Genoma Viral , Herpesvirus Humano 4/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/virologia , Latência Viral/genética , Regulação Viral da Expressão Gênica
2.
JAMA Netw Open ; 6(9): e2332556, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37695586

RESUMO

Importance: Despite the benefits of goals-of-care (GOC) communication, many hospitalized individuals never communicate their goals or preferences to clinicians. Objective: To assess whether a GOC video intervention delivered by palliative care educators (PCEs) increased the rate of GOC documentation. Design, Setting, and Participants: This pragmatic, stepped-wedge cluster randomized clinical trial included patients aged 65 years or older admitted to 1 of 14 units at 2 urban hospitals in New York and Boston from July 1, 2021, to October 31, 2022. Intervention: The intervention involved PCEs (social workers and nurses trained in GOC communication) facilitating GOC conversations with patients and/or their decision-makers using a library of brief, certified video decision aids available in 29 languages. Patients in the control period received usual care. Main Outcome and Measures: The primary outcome was GOC documentation, which included any documentation of a goals conversation, limitation of life-sustaining treatment, palliative care, hospice, or time-limited trials and was obtained by natural language processing. Results: A total of 10 802 patients (mean [SD] age, 78 [8] years; 51.6% male) were admitted to 1 of 14 hospital units. Goals-of-care documentation during the intervention phase occurred among 3744 of 6023 patients (62.2%) compared with 2396 of 4779 patients (50.1%) in the usual care phase (P < .001). Proportions of documented GOC discussions for Black or African American individuals (865 of 1376 [62.9%] vs 596 of 1125 [53.0%]), Hispanic or Latino individuals (311 of 548 [56.8%] vs 218 of 451 [48.3%]), non-English speakers (586 of 1059 [55.3%] vs 405 of 863 [46.9%]), and people living with Alzheimer disease and related dementias (520 of 681 [76.4%] vs 355 of 570 [62.3%]) were greater during the intervention phase compared with the usual care phase. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of older adults, a GOC video intervention delivered by PCEs resulted in higher rates of GOC documentation compared with usual care, including among Black or African American individuals, Hispanic or Latino individuals, non-English speakers, and people living with Alzheimer disease and related dementias. The findings suggest that this form of patient-centered care delivery may be a beneficial decision support tool. Trial Registration: ClinicalTrials.gov Identifier: NCT04857060.


Assuntos
Doença de Alzheimer , Humanos , Masculino , Idoso , Feminino , Objetivos , Comunicação , Documentação , Cuidados Paliativos
3.
J Virol ; 96(20): e0133622, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36218358

RESUMO

Nidogen 1 (NID1) is an important basement membrane protein secreted by many cell types. We previously found that human cytomegalovirus (HCMV) infection rapidly induced chromosome 1 breaks and that the basement membrane protein NID1, encoded near the 1q42 break site, was downregulated. We have now determined that the specific breaks in and of themselves did not regulate NID1, rather interactions between several viral proteins and the cellular machinery and DNA regulated NID1. We screened a battery of viral proteins present by 24 hours postinfection (hpi) when regulation was induced, including components of the incoming virion and immediate early (IE) proteins. Adenovirus (Ad) delivery of the tegument proteins pp71 and UL35 and the IE protein IE1 influenced steady-state (ss) NID1 levels. IE1's mechanism of regulation was unclear, while UL35 influenced proteasomal regulation of ss NID1. Real-time quantitative PCR (RT-qPCR) experiments determined that pp71 downregulated NID1 transcription. Surprisingly, WF28-71, a fibroblast clone that expresses minute quantities of pp71, suppressed NID1 transcription as efficiently as HCMV infection, resulting in the near absence of ss NID1. Sequence analysis of the region surrounding the 1q42 break sites and NID1 promoter revealed CCCTC-binding factor (CTCF) binding sites. Chromatin immunoprecipitation experiments determined that pp71 and CTCF were both bound at these two sites during HCMV infection. Expression of pp71 alone replicated this binding. Binding was observed as early as 1 hpi, and colocalization of pp71 and CTCF occurred as quickly as 15 min postinfection (pi) in infected cell nuclei. In fibroblasts where CTCF was knocked down, Adpp71 infection did not decrease NID1 transcription nor ss NID1 protein levels. Our results emphasize another aspect of pp71 activity during infection and identify this viral protein as a key contributor to HCMV's efforts to eliminate NID1. Further, we show, for the first time, direct interaction between pp71 and the cellular genome. IMPORTANCE We have found that human cytomegalovirus (HCMV) utilizes multiple viral proteins in multiple pathways to regulate a ubiquitous cellular basement membrane protein, nidogen-1 (NID1). The extent of the resources and the redundant methods that the virus has evolved to affect this control strongly suggest that its removal provides a life cycle advantage to HCMV. Our discoveries that one of the proteins that HCMV uses to control NID1, pp71, binds directly to the cellular DNA and can exert control when present in vanishingly small quantities may have broad implications in a wide range of infection scenarios. Dysregulation of NID1 in an immunocompetent host is not known to manifest complications during infection; however, in the naive immune system of a developing fetus, disruption of this developmentally critical protein could initiate catastrophic HCMV-induced birth defects.


Assuntos
Citomegalovirus , Proteínas Imediatamente Precoces , Humanos , Citomegalovirus/fisiologia , Proteínas Virais/metabolismo , Fator de Ligação a CCCTC/genética , Regulação Viral da Expressão Gênica , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Membrana Basal/metabolismo
4.
BMJ Open ; 12(7): e065236, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879001

RESUMO

INTRODUCTION: Despite the known benefit to patients and families, discussions about goals, values and preferences for medical care in advancing serious illness often do not occur. Many system and clinician factors, such as patient and clinician reticence and shortage of specialty palliative care teams, contribute to this lack of communication. To address this gap, we designed an intervention to promote goals-of-care conversations and palliative care referrals in the hospital setting by using trained palliative care educators and video decision aids. This paper presents the rationale, design and methods for a trial aimed at addressing barriers to goals-of-care conversations for hospitalised adults aged 65 and older and those with Alzheimer's disease and related Dementias, regardless of age. METHODS AND ANALYSIS: The Video Image about Decisions to Improve Ethical Outcomes with Palliative Care Educators is a pragmatic stepped wedge, cluster randomised controlled trial, which aims to improve and extend goals-of-care conversations in the hospital setting with palliative care educators trained in serious illness communication and video decision aids. The primary outcome is the proportion of patients with goals-of-care documentation in the electronic health record. We estimate that over 9000 patients will be included. ETHICS AND DISSEMINATION: The Institutional Review Board (IRB) at Boston Medical Center will serve as the single IRB of record for all regulatory and ethical aspects of this trial. BMC Protocol Number: H-41482. Findings will be presented at national meetings and in publications. This trial is registered at ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04857060; ClinicalTrials.gov.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Adulto , Comunicação , Hospitalização , Hospitais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Crit Care Med ; 49(10): 1739-1748, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34115635

RESUMO

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.


Assuntos
COVID-19/terapia , Intervenção em Crise/normas , Alocação de Recursos/métodos , Centros Médicos Acadêmicos/organização & administração , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , COVID-19/epidemiologia , Intervenção em Crise/métodos , Intervenção em Crise/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Massachusetts , Pessoa de Meia-Idade , Alocação de Recursos/estatística & dados numéricos , Estudos Retrospectivos , Provedores de Redes de Segurança/organização & administração , Provedores de Redes de Segurança/estatística & dados numéricos , Padrão de Cuidado/normas , Padrão de Cuidado/estatística & dados numéricos , População Urbana/estatística & dados numéricos
6.
Gastric Cancer ; 24(5): 1076-1088, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33929613

RESUMO

BACKGROUND AND AIMS: Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is the most common EBV-associated cancer and accounts for ~ 10% of all gastric cancers (GC). Epstein-Barr virus nuclear antigen 1 (EBNA1), which is critical for the replication and maintenance of the EBV latent genome, is consistently expressed in all EBVaGC tumors. We previously developed small molecule inhibitors of EBNA1. In this study, we investigated the efficacy and selectivity of an EBNA1 inhibitor in cell-based and animal xenograft models of EBV-positive and EBV-negative gastric carcinoma. METHODS: We tested the potency of an EBNA1 inhibitor, VK-1727, in vitro and in xenograft studies, using EBV-positive (SNU719 and YCCEL1) and EBV-negative (AGS and MKN74) GC cell lines. After treatment, we analyzed cell viability, proliferation, and RNA expression of EBV genes by RT-qPCR. RESULTS: Treatment with VK-1727 selectively inhibits cell cycle progression and proliferation in vitro. In animal studies, treatment with an EBNA1 inhibitor resulted in a significant dose-dependent decrease in tumor growth in EBVaGC xenograft models, but not in EBV-negative GC xenograft studies. Gene expression analysis revealed that short term treatment in cell culture tended towards viral gene activation, while long-term treatment in animal xenografts showed a significant decrease in viral gene expression. CONCLUSIONS: EBNA1 inhibitors are potent and selective inhibitors of cell growth in tissue culture and animal models of EBV-positive GC. Long-term treatment with EBNA1 inhibitors may lead to loss of EBV in mouse xenografts. These results suggest that pharmacological targeting of EBNA1 may be an effective strategy to treat patients with EBVaGC.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Animais , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Antígenos Nucleares do Vírus Epstein-Barr/genética , Herpesvirus Humano 4 , Xenoenxertos , Humanos , Camundongos , Neoplasias Gástricas/tratamento farmacológico
9.
PLoS Pathog ; 14(11): e1007394, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30395643

RESUMO

Latent membrane protein 1 (LMP1) is the major transforming protein of Epstein-Barr virus (EBV) and is critical for EBV-induced B-cell transformation in vitro. Poly(ADP-ribose) polymerase 1 (PARP1) regulates accessibility of chromatin, alters functions of transcriptional activators and repressors, and has been directly implicated in transcriptional activation. Previously we showed that LMP1 activates PARP1 and increases Poly(ADP-ribos)ylation (PARylation) through PARP1. Therefore, to identify targets of LMP1 that are regulated through PARP1, LMP1 was ectopically expressed in an EBV-negative Burkitt's lymphoma cell line. These LMP1-expressing cells were then treated with the PARP inhibitor olaparib and prepared for RNA sequencing. The LMP1/PARP targets identified through this RNA-seq experiment are largely involved in metabolism and signaling. Interestingly, Ingenuity Pathway Analysis of RNA-seq data suggests that hypoxia-inducible factor 1-alpha (HIF-1α) is an LMP1 target mediated through PARP1. PARP1 is acting as a coactivator of HIF-1α-dependent gene expression in B cells, and this co-activation is enhanced by LMP1-mediated activation of PARP1. HIF-1α forms a PARylated complex with PARP1 and both HIF-1α and PARP1 are present at promoter regions of HIF-1α downstream targets, leading to accumulation of positive histone marks at these regions. Complex formation, PARylation and binding of PARP1 and HIF-1α at promoter regions of HIF-1α downstream targets can all be attenuated by PARP1 inhibition, subsequently leading to a buildup of repressive histone marks and loss of positive histone marks. In addition, LMP1 switches cells to a glycolytic 'Warburg' metabolism, preferentially using aerobic glycolysis over mitochondrial respiration. Finally, LMP1+ cells are more sensitive to PARP1 inhibition and, therefore, targeting PARP1 activity may be an effective treatment for LMP1+ EBV-associated malignancies.


Assuntos
Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas da Matriz Viral/metabolismo , Linfócitos B/virologia , Linhagem Celular Tumoral , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Fator 1 Induzível por Hipóxia/genética , Ftalazinas/farmacologia , Piperazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Transdução de Sinais , Ativação Transcricional , Proteínas da Matriz Viral/genética
10.
J Virol ; 92(18)2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29976663

RESUMO

Epstein Barr virus (EBV) is a potentially oncogenic gammaherpesvirus that establishes a chronic, latent infection in memory B cells. The EBV genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type. CTCF is posttranslationally modified by the host enzyme PARP1. PARP1, or poly(ADP-ribose) polymerase 1, catalyzes the transfer of a poly(ADP-ribose) (PAR) moiety from NAD+ onto acceptor proteins, including itself, histone proteins, and CTCF. PARylation of CTCF by PARP1 can affect CTCF's insulator activity, DNA binding capacity, and ability to form chromatin loops. Both PARP1 and CTCF have been implicated in the regulation of EBV latency and lytic reactivation. Thus, we predicted that pharmacological inhibition with PARP1 inhibitors would affect EBV latency type through a chromatin-specific mechanism. Here, we show that PARP1 and CTCF colocalize at specific sites throughout the EBV genome and provide evidence to suggest that PARP1 acts to stabilize CTCF binding and maintain the open chromatin landscape at the active Cp promoter during type III latency. Further, PARP1 activity is important in maintaining latency type-specific viral gene expression. The data presented here provide a rationale for the use of PARP inhibitors in the treatment of EBV-associated cancers exhibiting type III latency and ultimately could contribute to an EBV-specific treatment strategy for AIDS-related or posttransplant lymphomas.IMPORTANCE EBV is a human gammaherpesvirus that infects more than 95% of individuals worldwide. Upon infection, EBV circularizes as an episome and establishes a chronic, latent infection in B cells. In doing so, the virus utilizes host cell machinery to regulate and maintain the viral genome. In otherwise healthy individuals, EBV infection is typically nonpathological; however, latent infection is potentially oncogenic and is responsible for 1% of human cancers. During latent infection, EBV expresses specific sets of proteins according to the given latency type, each of which is associated with specific types of cancers. For example, type III latency, in which the virus expresses its full repertoire of latent proteins, is characteristic of AIDS-associated and posttransplant lymphomas associated with EBV infection. Understanding how viral latency type is regulated at the chromatin level may reveal potential targets for EBV-specific pharmacological intervention in EBV-associated cancers.


Assuntos
Fator de Ligação a CCCTC/genética , Herpesvirus Humano 4/fisiologia , Poli(ADP-Ribose) Polimerase-1/genética , Latência Viral/genética , Fator de Ligação a CCCTC/metabolismo , Linhagem Celular Tumoral , Cromatina/genética , Cromatina/metabolismo , Epigenômica , Regulação Viral da Expressão Gênica , Genoma Viral , Herpesvirus Humano 4/química , Herpesvirus Humano 4/genética , Humanos , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Regiões Promotoras Genéticas , Transcrição Gênica , Latência Viral/efeitos dos fármacos
11.
Acad Med ; 93(9): 1341-1347, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29877915

RESUMO

PURPOSE: Nongeriatricians must acquire skills and knowledge in geriatric medicine to ensure coordinated care of older adults' complex conditions by interspecialty and interprofessional teams. Chief residents (CRs) are an ideal target for an educational intervention. This study examined whether the Boston Medical Center Chief Resident Immersion Training (CRIT) in the Care of Older Adults was replicable at diverse medical institutions. METHOD: Between 2008 and 2010, 12 institutions in 11 states received funding, technical support, and a common program model. Each implemented 2.5-day CRITs, consisting of a patient case, geriatrics-related lectures, CR leadership sessions, action project planning, and networking time. Site faculty conducted 21 CRITs for 295 CRs representing 28 specialties. CRs completed knowledge pre- and posttests, and self-report baseline and six-month follow-up surveys. Outcome measures were change in pre- and posttest score, and change from baseline to six months in self-reported surveys. RESULTS: Response rate for CRs was 99% (n = 293) for the pre-post tests and 78% (n = 231) for matchable baseline and follow-up surveys. Participants' knowledge increased from 6.32 to 8.39 (P < .001) averaged from 12 questions. CRs' self-reported ability to apply clinical problem-solving skills to older patients (P < .001), number of geriatrics topics taught (P < .001), frequency of geriatrician consultations (P = .017), confidence in leadership skills (P < .001), and confidence to conduct CR work (P < .001) increased from baseline to follow-up. CONCLUSIONS: CRIT is an innovative way to give nongeriatricians knowledge and skills to treat complex older patients.


Assuntos
Geriatria/educação , Internato e Residência/métodos , Idoso , Competência Clínica , Avaliação Educacional , Humanos , Inquéritos e Questionários
12.
Oncotarget ; 9(12): 10585-10605, 2018 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-29535829

RESUMO

The enzyme Poly(ADP-ribose) polymerase 1 (PARP1) plays a very important role in the DNA damage response, but its role in numerous aspects is not fully understood. We recently showed that in the absence of DNA damage, PARP1 regulates the expression of the chromatin-modifying enzyme EZH2. Work from other groups has shown that EZH2 participates in the DNA damage response. These combined data suggest that EZH2 could be a target of PARP1 in both untreated and genotoxic agent-treated conditions. In this work we tested the hypothesis that, in response to DNA damage, PARP1 regulates EZH2 activity. Here we report that PARP1 regulates EZH2 activity after DNA damage. In particular, we find that EZH2 is a direct target of PARP1 upon induction of alkylating and UV-induced DNA damage in cells and in vitro. PARylation of EZH2 inhibits EZH2 histone methyltransferase (H3K27me) enzymatic activity. We observed in cells that the induction of PARP1 activity by DNA alkylating agents decreases the association of EZH2 with chromatin, and PARylation of histone H3 reduces EZH2 affinity for its target histone H3. Our findings establish that PARP1 and PARylation are important regulators of EZH2 function and link EZH2-mediated heterochromatin formation, DNA damage and PARylation. These findings may also have clinical implications, as they suggest that inhibitors of EZH2 can improve anti-tumor effects of PARP1 inhibitors in BRCA1/2-deficient cancers.

13.
Virology ; 507: 220-230, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28456021

RESUMO

The Epstein Barr virus (EBV) genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type, and in other herpesviruses, loss of CTCF binding at specific regions correlates with viral reactivation. Here, we demonstrate that binding of PARP1, an important cofactor of CTCF, at the BZLF1 lytic switch promoter restricts EBV reactivation. Knockdown of PARP1 in the Akata-EBV cell line significantly increases viral copy number and lytic protein expression. Interestingly, CTCF knockdown has no effect on viral reactivation, and CTCF binding across the EBV genome is largely unchanged following reactivation. Moreover, EBV reactivation attenuates PARP activity, and Zta expression alone is sufficient to decrease PARP activity. Here we demonstrate a restrictive function of PARP1 in EBV lytic reactivation.


Assuntos
Infecções por Vírus Epstein-Barr/enzimologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Regiões Promotoras Genéticas , Transativadores/genética , Ativação Viral , Linhagem Celular , Infecções por Vírus Epstein-Barr/genética , Regulação Viral da Expressão Gênica , Herpesvirus Humano 4/genética , Interações Hospedeiro-Patógeno , Humanos , Poli(ADP-Ribose) Polimerase-1/genética , Ligação Proteica , Transativadores/metabolismo , Latência Viral
14.
J Aging Res ; 2014: 873043, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24678422

RESUMO

Following up on recommendations made at the time of a hospital discharge is important to patient safety. While data is lacking, specifically around the transition of patient to nursing home, it has been postulated that missed items such as laboratory tests may result in adverse patient outcomes. To determine the extent of this problem, a retrospective cohort study of subjects discharged from an academic medical center and admitted to nursing homes (NH) was followed to determine the type of discharge recommendations and the rate of completion. In addition, for the purpose of generalizability, the 30-day hospital readmission rate was calculated. 152 recommendations were made on 51 subjects. Almost a quarter of the recommendations made by the hospital discharging team were not acted upon. Furthermore, for the majority of those recommendations that were not acted upon, a reason could not be determined. In concert with national data, 20% of the subjects returned to the hospital within 30 days. Further investigation is warranted to determine if an association exists between missed recommendations and hospital readmission from the nursing home setting.

15.
Am J Med Qual ; 28(1): 8-15, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22684011

RESUMO

Rehospitalizations may indicate care quality problems. The authors conducted a retrospective cohort study of adults aged 65 years and older, comparing 30-day rehospitalization rates. Rates were compared for comprehensive geriatrics practice patients and for patients receiving usual general medical care. The unadjusted 30-day rehospitalization rate was 18% overall, 21% for geriatrics patients cared for on the geriatrics inpatient service, 22% for geriatrics practice patients on general medical services (GMSs), and 17% for older patients on GMS. Compared with older adults discharged from a GMS, geriatrics patients on the geriatrics service had an adjusted odds ratio for readmission of 1.00 (95% confidence interval = 0.88-1.13). Despite greater frailty, patients cared for in an interdisciplinary geriatrics practice were no more likely to be rehospitalized than adults receiving "usual care," when adjusted for age and disease burden. Incomplete adjustment may account for this finding, which did not confirm the hypothesis that comprehensive geriatrics care would yield fewer rehospitalizations.


Assuntos
Readmissão do Paciente , Idoso , Idoso de 80 Anos ou mais , Boston , Feminino , Serviços de Saúde para Idosos/normas , Humanos , Masculino , Modelos Organizacionais , Readmissão do Paciente/normas , Guias de Prática Clínica como Assunto/normas , Qualidade da Assistência à Saúde/normas , Estudos Retrospectivos
16.
J Am Geriatr Soc ; 56(6): 1140-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18410320

RESUMO

Chief residents (CRs) play a crucial role in training residents and students but may have limited geriatrics training or formal preparation for their CR role. A 2-day off-site chief resident immersion training (CRIT) addressed these challenges. Objectives were to foster collaboration between disciplines in the management of complex older patients, increase knowledge of geriatrics principles to incorporate into teaching, enhance leadership skills, and help CRs develop an achievable project for implementation in their CR year. Three cohorts totaling 47 trainees and 18 faculty mentors from 13 medical and surgical disciplines participated over 3 successive years. The curriculum, developed and taught by a multidisciplinary team, featured an interactive surgical case, mini-lectures on geriatrics topics, seminars to enhance teaching and leadership skills, and one-on-one mentoring to develop a project in geriatric care or education. Evaluation included pre- and postprogram tests and self-report surveys and two follow-up surveys or interviews. In 2006 and 2007, scores on a 12-item objective knowledge test increased significantly (P<.001) from before to immediately after CRIT. Self-report knowledge and confidence in teaching geriatrics also increased significantly (P<.05) in all formally covered topics. Mean enhancement of CR skills was 4.3 (1=not at all, 5=very much). Eleven months after CRIT, all but five CRs had implemented at least part of their action projects. CRs reported improved care of older patients, better leadership skills, more and better geriatrics teaching, and more collaboration between disciplines. A 2-day interactive program for CRs can increase institutional capacity regarding geriatrics teaching and care of elderly patients across medical specialties.


Assuntos
Geriatria/educação , Internato e Residência , Liderança , Mentores , Idoso , Boston , Avaliação Educacional , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Relações Interprofissionais , Avaliação de Programas e Projetos de Saúde
17.
J Am Geriatr Soc ; 55(10): 1656-62, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17714460

RESUMO

The management of older patients with chronic medical conditions dominates medical practice. Cardiovascular disease (CVD) and diabetes mellitus type 2 (DM) in patients aged 65 and older have reached epidemic proportions. Using elements of the Chronic Care Model (CCM), a quality improvement project was undertaken to restructure the Geriatric Ambulatory Practice at Boston Medical Center, Boston's safety net hospital, to improve the quality of care for CVD and diabetes mellitus. Two hundred eighty-three eligible patients who had CVD, DM, or both were identified. The 39-month project period was divided into a 12-month baseline period and three follow-up periods. The multifaceted intervention consisted of development of a disease registry that centralized clinical information, implementation of an electronic medical record, patient education, physician education regarding evidence-based guidelines, feedback of provider-specific and practice data to physicians, and implementation of a foot examination protocol. Clinical measures included glycosylated hemoglobin, a diabetic foot examination, lipid profile, and blood pressure measurement. These were collected at baseline and at each patient visit for the entire project period. The average age of all patients was 76; 64% were female, 64% were African American, 72% had Medicare, and 22% had state subsidized medical insurance. Patients in all disease groups showed significant improvement in all clinical measures over time, independent of the frequency of visits. Using the CCM as a quality improvement framework can improve clinical measures for older urban minority populations with CVD and DM.


Assuntos
Doenças Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/terapia , Serviços de Saúde para Idosos/estatística & dados numéricos , Qualidade da Assistência à Saúde , Idoso , Idoso de 80 Anos ou mais , Boston , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Serviços de Saúde para Idosos/organização & administração , Humanos , Masculino , Pessoa de Meia-Idade , População Urbana
18.
J Am Geriatr Soc ; 53(3): 516-21, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15743299

RESUMO

As the size of the aged American population increases, so too does the shortage of trained providers in geriatrics. Educational strategies to train physicians at all levels of experience within adult medical and surgical disciplines are needed to complement fellowship training, given the small size of most academic faculties in geriatrics. This article describes a unique faculty development program that creates geriatrically oriented faculty in multiple disciplines. The Boston University Center of Excellence in Geriatrics (COE), funded by the John A. Hartford Foundation, has trained 25 faculty members. Four to six scholars enter the program each year and participate in the COE 1 day per week. Nine months are spent in four content modules-Geriatrics Content, Clinical Teaching, Evidence-based Medicine, and Health Care Systems; 3 months are spent in supervised scholarly activities and clinical settings. A self-report questionnaire and a structured interview were used to evaluate the outcomes of participation in the COE. The results from the first 4 years of the program are reported. The response rate was 83% for the self-report questionnaire and 75% for the structured interview. The results indicate that the COE is effective in improving scholars' assessment and management of older patients. The structured interview revealed that the COE program promotes the integration of geriatrics into clinical teaching at the medical student and resident level. Participants also completed scholarly projects in geriatrics. This program effectively trains faculty scholars to better care for older adults and to teach others to do likewise.


Assuntos
Atitude do Pessoal de Saúde , Mobilidade Ocupacional , Currículo , Geriatria/educação , Docentes de Medicina , Relações Médico-Paciente , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários
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