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2.
J Med Internet Res ; 25: e46773, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37490327

RESUMO

In 2021, Canada Health Infoway and the University of Victoria's Gender, Sex, and Sexual Orientation Research Team hosted a series of discussions to successfully and safely modernize gender, sex, and sexual orientation information practices within digital health systems. Five main topic areas were covered: (1) terminology standards; (2) digital health and electronic health record functions; (3) policy and practice implications; (4) primary care settings; and (5) acute and tertiary care settings. In this viewpoint paper, we provide priorities for future research and implementation projects and recommendations that emerged from these discussions.


Assuntos
Registros Eletrônicos de Saúde , Sistemas de Informação em Saúde , Políticas , Feminino , Humanos , Masculino , Canadá , Comportamento Sexual , Identidade de Gênero
3.
Artigo em Inglês | MEDLINE | ID: mdl-37068924

RESUMO

OBJECTIVES: Haematology patients are more likely to receive high intensity care near end of life (EOL) than patients with solid malignancy. Previous authors have suggested indicators of quality EOL for haematology patients, based on a solid oncology model. We conducted a retrospective chart review with the objectives of (1) determining our performance on these quality EOL indicators, (2) describing the timing of level of intervention (LOI) discussion and palliative care (PC) consultation prior to death and (3) evaluating whether goals of therapy (GOT), PC consultation and earlier LOI discussion are predictors of quality EOL. METHODS: We identified patients who died from haematological malignancies between April 2014 and March 2016 (n=319) at four participating McGill University hospitals and performed retrospective chart reviews. RESULTS: We found that 17% of patients were administered chemotherapy less than 14 days prior to death, 20% of patients were admitted to intensive care, 14% were intubated and 5% were resuscitated less than 30 days prior to death, 18% of patients received blood transfusion less than 7 days prior to death and 67% of patients died in an acute care setting. LOI discussion and PC consultation occurred a median of 22 days (IQR 7-103) and 9 days (IQR 3-19) before death. Patients with non-curative GOT, PC consultation or discussed LOI were significantly less likely to have high intensity EOL outcomes. CONCLUSIONS: In this study, we demonstrate that LOI discussions, PC consults and physician established GOT are associated with quality EOL outcomes for patients with haematological malignancies.

4.
Blood ; 140(21): 2248-2260, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-35839452

RESUMO

Here, we report the first comparative analysis of patient-reported outcomes (PROs) with chimeric antigen receptor T-cell therapy vs standard-of-care (SOC) therapy in second-line relapsed/refractory large B-cell lymphoma (R/R LBCL) from the pivotal randomized phase 3 ZUMA-7 study of axicabtagene ciloleucel (axi-cel) vs SOC. PRO instruments were administered at baseline, day 50, day 100, day 150, month 9, and every 3 months from randomization until 24 months or an event-free survival event. The quality of life (QoL) analysis set comprised patients with a baseline and ≥1 follow-up PRO completion. Prespecified hypotheses for Quality of Life Questionnaire-Core 30 (QLQ-C30) physical functioning, global health status/QoL, and EQ-5D-5L visual analog scale (VAS) were tested using mixed-effects models with repeated measures. Clinically meaningful changes were defined as 10 points for QLQ-C30 and 7 for EQ-5D-5L VAS. Among 359 patients, 296 (165 axi-cel, 131 SOC) met inclusion criteria for QoL analysis. At day 100, statistically significant and clinically meaningful differences in mean change of scores from baseline were observed favoring axi-cel over SOC for QLQ-C30 global health status/QoL (estimated difference 18.1 [95% confidence interval (CI), 12.3-23.9]), physical functioning (13.1 [95% CI, 8.0-18.2]), and EQ-5D-5L VAS (13.7 [95% CI, 8.5-18.8]; P < .0001 for all). At day 150, scores significantly favored axi-cel vs SOC for global health status/QoL (9.8 [95% CI, 2.6-17.0]; P = .0124) and EQ-5D-5L VAS (11.3 [95% CI, 5.4-17.1]; P = .0004). Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03391466.


Assuntos
Linfoma Difuso de Grandes Células B , Qualidade de Vida , Humanos , Antígenos CD19/uso terapêutico , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente
5.
J Am Med Inform Assoc ; 29(2): 379-384, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34605910

RESUMO

Most digital health systems (DHS) are unable to capture gender, sex, and sexual orientation (GSSO) data beyond a single binary attribute with female and male options. This binary system discourages access to preventative screening and gender-affirming care for sexual and gender minority (SGM) people. We conducted this 1-year multi-method project and cocreated an action plan to modernize GSSO information practices in Canadian DHS. The proposed actions are to: (1) Envisage an equity- and SGM-oriented health system; (2) Engage communities and organizations to modernize GSSO information practices in DHS; (3) Establish an inclusive GSSO terminology; (4) Enable DHS to collect, use, exchange, and reuse standardized GSSO data; (5) Integrate GSSO data collection and use within organizations; (6) Educate staff to provide culturally competent care and inform patients on the need for GSSO data; and (7) Establish a central hub to coordinate efforts.


Assuntos
Minorias Sexuais e de Gênero , Canadá , Assistência à Saúde Culturalmente Competente , Feminino , Identidade de Gênero , Humanos , Masculino , Comportamento Sexual
6.
J Am Med Inform Assoc ; 29(2): 354-363, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34613410

RESUMO

OBJECTIVE: Accurate representation of clinical sex and gender identity in interoperable clinical systems is a major challenge for organizations intent on improving outcomes for sex- and gender-marginalized people. Improved data collection has been hindered by the historical approach that presumed a single, often binary, datum was sufficient. We describe the Health Level Seven International (HL7) Gender Harmony logical model that proposes an improved approach. MATERIALS AND METHODS: The proposed solution was developed via an American National Standards Institute (ANSI)-certified collaborative balloted process. As an HL7 Informative Document, it is an HL7 International-balloted consensus on the subject of representing sex and representing gender in clinical systems based on work of the gender harmony project led by the HL7 Vocabulary Work Group. RESULTS: The Gender Harmony Model is a logical model that provides a standardized approach that is both backwards-compatible and an improvement to the meaningful capture of gender identity, recorded sex or recorded gender, a sex for clinical use, the name to use, and pronouns that are affirmative and inclusive of gender-marginalized people. CONCLUSION: Most clinical systems and current standards in health care do not meaningfully address, nor do they consistently represent, sex and gender diversity, which has impeded interoperability and led to suboptimal health care. The Gender Harmony Project was formed to create more inclusive health information exchange standards to enable a safer, higher-quality, and embracing healthcare experience. The Gender Harmony Model provides the informative guidance for standards developers to implement a more thorough technical design that improves the narrow binary design used in many legacy clinical systems.


Assuntos
Identidade de Gênero , Troca de Informação em Saúde , Atenção à Saúde , Feminino , Nível Sete de Saúde , Humanos , Masculino
8.
J Med Internet Res ; 23(6): e30764, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34086590

RESUMO

[This corrects the article DOI: 10.2196/20050.].

9.
JMIR Med Inform ; 9(2): e25467, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33455901

RESUMO

BACKGROUND: Outdated gender, sex, and sexual orientation (GSSO) information practices in health care contribute to health inequities for sexual and gender minorities (SGMs). Governments, statistics agencies, and health care organizations are developing and implementing modernized practices that support health equity for SGMs. Extending our work, we conducted a rapid review of grey literature to explore information practices that support quality health care for SGMs. OBJECTIVE: The aim of this rapid review of grey literature was to elucidate modern GSSO information practices from leading agencies for adaptation, adoption, and application by health care providers and organizations seeking to modernize outdated GSSO information practices that contribute to health inequities among SGMs. METHODS: We searched MEDLINE and Google from 2015 to 2020 with terms related to gender, sex, sexual orientation, and electronic health/medical records for English-language grey literature resources including government and nongovernment organization publications, whitepapers, data standards, toolkits, health care organization and health quality practice and policy guides, conference proceedings, unpublished academic work, and statistical papers. Peer-reviewed journal articles were excluded, as were resources irrelevant to information practices. We also screened the reference sections of included articles for additional resources, and canvassed a working group of international topic experts for additional relevant resources. Duplicates were eliminated. ATLAS.ti was used to support analysis. Themes and codes were developed through an iterative process of writing and discussion with the research team. RESULTS: Twenty-six grey literature resources met the inclusion criteria. The overarching themes that emerged from the literature were the interrelated behaviors, attitudes, and policies that constitute SGM cultural competence as follows: shared language with unambiguous definitions of GSSO concepts; welcoming and inclusive care environments and affirming practices to reduce barriers to access; health care policy that supports competent health care; and adoption of modernized GSSO information practices and electronic health record design requirements that address invisibility in health data. CONCLUSIONS: Health equity for SGMs requires systemic change. Binary representation of sex and gender in electronic health records (EHRs) obfuscates natural and cultural diversity and, in the context of health care, places SGM patients at risk of clinical harm because it leads to clinical assumptions. Agencies and agents in health care need to be equipped with the knowledge and tools needed to cultivate modern attitudes, policies, and practices that enable health equity for SGMs. Adopting small but important changes in the language and terminology used in technical and social health care systems is essential for institutionalizing SGM competency. Modern GSSO information practices depend on and reinforce SGM competency in health care.

10.
J Med Internet Res ; 22(11): e20050, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174858

RESUMO

BACKGROUND: Historically, the terms sex and gender have been used interchangeably as a binary attribute to describe a person as male or female, even though there is growing recognition that sex and gender are distinct concepts. The lack of sex and gender delineation in electronic health records (EHRs) may be perpetuating the inequities experienced by the transgender and gender nonbinary (TGNB) populations. OBJECTIVE: This study aims to conduct an environmental scan to understand how sex and gender are defined and implemented in existing Canadian EHRs and current international health information standards. METHODS: We examined public information sources on sex and gender definitions in existing Canadian EHRs and international standards communities. Definitions refer to data element names, code systems, and value sets in the descriptions of EHRs and standards. The study was built on an earlier environment scan by Canada Health Infoway, supplemented with sex and gender definitions from international standards communities. For the analysis, we examined the definitions for clarity, consistency, and accuracy. We also received feedback from a virtual community interested in sex-gender EHR issues. RESULTS: The information sources consisted of public website descriptions of 52 databases and 55 data standards from 12 Canadian entities and 10 standards communities. There are variations in the definition and implementation of sex and gender in Canadian EHRs and international health information standards. There is a lack of clarity in some sex and gender concepts. There is inconsistency in the data element names, code systems, and value sets used to represent sex and gender concepts across EHRs. The appropriateness and adequacy of some value options are questioned as our societal understanding of sexual health evolves. Outdated value options raise concerns about current EHRs supporting the provision of culturally competent, safe, and affirmative health care. The limited options also perpetuate the inequities faced by the TGNB populations. The expanded sex and gender definitions from leading Canadian organizations and international standards communities have brought challenges in how to migrate these definitions into existing EHRs. We proposed 6 high-level actions, which are to articulate the need for this work, reach consensus on sex and gender concepts, reach consensus on expanded sex and gender definitions in EHRs, develop a coordinated action plan, embrace EHR change from socio-organizational and technical aspects to ensure success, and demonstrate the benefits in tangible terms. CONCLUSIONS: There are variations in sex and gender concepts across Canadian EHRs and the health information standards that support them. Although there are efforts to modernize sex and gender concept definitions, we need decisive and coordinated actions to ensure clarity, consistency, and competency in the definition and implementation of sex and gender concepts in EHRs. This work has implications for addressing the inequities of TGNB populations in Canada.


Assuntos
Registros Eletrônicos de Saúde/normas , Informática Médica/métodos , Feminino , Identidade de Gênero , Humanos , Masculino , Caracteres Sexuais
11.
J Am Med Inform Assoc ; 27(11): 1774-1783, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32935124

RESUMO

OBJECTIVE: The lack of precise and inclusive gender, sex, and sexual orientation (GSSO) data in electronic health records (EHRs) is perpetuating inequities of sexual and gender minorities (SGM). We conducted a rapid review on how GSSO documentation in EHRs should be modernized to improve the health of SGM. MATERIALS AND METHODS: We searched MEDLINE from 2015 to 2020 with terms for gender, sex, sexual orientation, and electronic health/medical records. Only literature reviews, primary studies, and commentaries from peer-reviewed journals in English were included. Two researchers screened citations and reviewed articles with help from a third to reach consensus. Covidence, Excel, and Atlas-TI were used to track articles, extract data, and synthesize findings, respectively. RESULTS: Thirty-five articles were included. The 5 themes to modernize GSSO documentation in EHRs were (1) creating an inclusive, culturally competent environment with precise terminology and standardized data collection; (2) refining guidelines for identifying and matching SGM patients with their care needs; (3) improving patient-provider relationships by addressing patient rights and provider competencies; (4) recognizing techno-socio-organizational aspects when implementing GSSO in EHRs; and (5) addressing invisibility of SGM by expanding GSSO research. CONCLUSIONS: The literature on GSSO documentation in EHRs is expanding. While this trend is encouraging, there are still knowledge gaps and practical challenges to enabling meaningful changes, such as organizational commitments to ensure affirming environments, and coordinated efforts to address technical, organizational, and social aspects of modernizing GSSO documentation. The adoption of an inclusive EHR to meet SGM needs is a journey that will evolve over time.


Assuntos
Registros Eletrônicos de Saúde , Identidade de Gênero , Sexo , Comportamento Sexual , Minorias Sexuais e de Gênero , Registros Eletrônicos de Saúde/normas , Feminino , Humanos , Masculino , Política Organizacional
12.
Toxicol Lett ; 160(2): 158-70, 2006 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-16112521

RESUMO

Very little is known concerning the toxicity of antimony, despite its commercial use as a flame retardant and medical use as a treatment for parasitic infections. Our previous studies show that antimony trioxide (Sb(2)O(3)) induces growth inhibition in patient-derived acute promyelocytic leukemia (APL) cell lines, a disease in which a related metal, arsenic trioxide (As(2)O(3)), is used clinically. However, signaling pathways initiated by Sb(2)O(3) treatment remain undefined. Here, we show that Sb(2)O(3) treatment of APL cells is associated with increased apoptosis as well as differentiation markers. Sb(2)O(3)-induced reactive oxygen species (ROS) correlated with increased apoptosis. In addition, when we decreased the buffering capacity of the cell by depleting glutathione, ROS production and apoptosis was enhanced. Arsenic-resistant APL cells with increased glutathione levels exhibited increased cross-resistance to Sb(2)O(3). Based on studies implicating c-jun kinase (JNK) in the mediation of the response to As(2)O(3), we investigated the role for JNK in Sb(2)O(3)-induced apoptosis. Sb(2)O(3) activates JNK and its downstream target, AP-1. In fibroblasts with a genetic deletion in SEK1, an upstream regulator of JNK, Sb(2)O(3)-induced growth inhibition as well as JNK activation was decreased. These data suggest roles for ROS and the SEK1/JNK pathway in the cytotoxicity associated with Sb(2)O(3) exposure.


Assuntos
Antimônio/toxicidade , Apoptose/efeitos dos fármacos , MAP Quinase Quinase 4/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Células HeLa , Humanos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo
13.
Blood ; 103(9): 3496-502, 2004 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-14701702

RESUMO

Arsenic trioxide induces c-jun N-terminal kinase (JNK) activation and apoptosis in acute promyelocytic leukemia (APL), where it has major clinical activity, but whether JNK is necessary to induce apoptosis is unknown. To clarify this necessity, we established 2 arsenic trioxide (As(2)O(3))-resistant subclones of the APL cell line, NB4. Both resistant lines showed little activation of JNK1 following treatment with As(2)O(3), even at doses sufficient to elicit robust activation in NB4 cells. One mechanism of resistance in these cells is up-regulated glutathione (GSH) content, and GSH depletion by l-buthionine-[S,R]-sulfoximine (BSO) restores JNK activation and As(2)O(3) sensitivity. This correlation between JNK activation and apoptosis led us to test whether inhibition of JNK would protect cells from As(2)O(3)-induced apoptosis. SEK1(-/-) mouse embryo fibroblasts (MEFs) showed diminished JNK activation following As(2)O(3) treatment and were protected from As(2)O(3)-induced but not doxorubicin-induced apoptosis. Furthermore, treatment of arsenic trioxide-sensitive APL cells with the JNK inhibitor, dicumarol, significantly increased growth and survival in response to As(2)O(3) but did not protect cells from doxorubicin. Together, these data support an essential role for JNK signaling in the induction of growth inhibition and apoptosis by As(2)O(3) and suggest that activating JNK may provide a therapeutic advantage in the treatment of cancers that do not respond to arsenic alone.


Assuntos
Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Leucemia Promielocítica Aguda/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxidos/farmacologia , Animais , Trióxido de Arsênio , Linhagem Celular Tumoral , Células Cultivadas , Células Clonais/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática/efeitos dos fármacos , Glutationa/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno , Camundongos , Camundongos Knockout , Proteína Quinase 8 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Receptor EphA4/genética
14.
Semin Hematol ; 39(2 Suppl 1): 3-7, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12012315

RESUMO

The chimeric protein encoded by the PML-RAR alpha gene that is pathognomonic of acute promyelocytic leukemia (APL) causes the arrest of myeloid cell development at the promyelocyte stage, leading to an accumulation of abnormal promyelocytes in the bone marrow. Differentiation therapy with all-trans retinoic acid (ATRA) is used routinely in patients with APL, but ATRA is not the only agent in clinical use that promotes differentiation of the abnormal clone. Arsenic trioxide (ATO) has been shown to cause degradation of PML-RAR alpha, promoting differentiation. APL cells are extremely sensitive to ATO, which has shown good clinical activity at low doses in patients with relapsed APL. However, degradation of PML-RAR alpha may not be wholly responsible for the great sensitivity of APL cells to ATO, which also acts through the intracellular environment to influence apoptosis, differentiation, growth arrest, and angiogenesis. ATO can act at several points in mitochondrially induced apoptosis, including degradation of peroxides and interaction with glutathione (GSH)-related enzymes. Subclones that are resistant to ATO have been used to demonstrate that sensitivity can be restored by reducing the cellular GSH content. GSH can be reduced using agents such as buthionine sulfoximine (BSO) and ascorbic acid. The key factors that determine the ATO sensitivity of cells and control ATO-induced apoptosis have not yet been defined. It has been proposed that ATO acts through activation of Jun N-terminal kinase (JNK), activator protein-1, and inhibition of dual-specificity phosphatases, and evidence is accumulating that JNK activation is an important event in arsenic-induced apoptosis. Further research is required to determine the exact pathways through which the cytotoxic actions of ATO are mediated.


Assuntos
Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Óxidos/uso terapêutico , Animais , Apoptose , Trióxido de Arsênio , Diferenciação Celular , Divisão Celular , Glutationa/metabolismo , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Proteínas de Neoplasias/genética , Neovascularização Patológica , Proteínas de Fusão Oncogênica/genética , Recidiva
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