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1.
N Engl J Med ; 388(8): 694-705, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36812433

RESUMO

BACKGROUND: Valoctocogene roxaparvovec delivers a B-domain-deleted factor VIII coding sequence with an adeno-associated virus vector to prevent bleeding in persons with severe hemophilia A. The findings of a phase 3 study of the efficacy and safety of valoctocogene roxaparvovec therapy evaluated after 52 weeks in men with severe hemophilia A have been published previously. METHODS: We conducted an open-label, single-group, multicenter, phase 3 trial in which 134 men with severe hemophilia A who were receiving factor VIII prophylaxis received a single infusion of 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight. The primary end point was the change from baseline in the annualized rate of treated bleeding events at week 104 after receipt of the infusion. The pharmacokinetics of valoctocogene roxaparvovec were modeled to estimate the bleeding risk relative to the activity of transgene-derived factor VIII. RESULTS: At week 104, a total of 132 participants, including 112 with data that were prospectively collected at baseline, remained in the study. The mean annualized treated bleeding rate decreased by 84.5% from baseline (P<0.001) among the participants. From week 76 onward, the trajectory of the transgene-derived factor VIII activity showed first-order elimination kinetics; the model-estimated typical half-life of the transgene-derived factor VIII production system was 123 weeks (95% confidence interval, 84 to 232). The risk of joint bleeding was estimated among the trial participants; at a transgene-derived factor VIII level of 5 IU per deciliter measured with chromogenic assay, we expected that participants would have 1.0 episode of joint bleeding per year. At 2 years postinfusion, no new safety signals had emerged and no new serious adverse events related to treatment had occurred. CONCLUSIONS: The study data show the durability of factor VIII activity and bleeding reduction and the safety profile of valoctocogene roxaparvovec at least 2 years after the gene transfer. Models of the risk of joint bleeding suggest that the relationship between transgene-derived factor VIII activity and bleeding episodes is similar to that reported with the use of epidemiologic data for persons with mild-to-moderate hemophilia A. (Funded by BioMarin Pharmaceutical; GENEr8-1 ClinicalTrials.gov number, NCT03370913.).


Assuntos
Fator VIII , Hemofilia A , Humanos , Masculino , Fator VIII/uso terapêutico , Técnicas de Transferência de Genes , Meia-Vida , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/prevenção & controle , Proteínas Recombinantes de Fusão/uso terapêutico
2.
N Engl J Med ; 387(3): 237-247, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35857660

RESUMO

BACKGROUND: FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B. METHODS: In this multicenter, open-label, phase 1-2 trial, we assessed the safety and efficacy of varying doses of FLT180a in patients with severe or moderately severe hemophilia B (factor IX level, ≤2% of normal value). All the patients received glucocorticoids with or without tacrolimus for immunosuppression to decrease the risk of vector-related immune responses. After 26 weeks, patients were enrolled in a long-term follow-up study. The primary end points were safety and efficacy, as assessed by factor IX levels at week 26. RESULTS: Ten patients received one of four FLT180a doses of vector genomes (vg) per kilogram of body weight: 3.84×1011 vg, 6.40×1011 vg, 8.32×1011 vg, or 1.28×1012 vg. After receiving the infusion, all the patients had dose-dependent increases in factor IX levels. At a median follow-up of 27.2 months (range, 19.1 to 42.4), sustained factor IX activity was observed in all the patients except one, who resumed factor IX prophylaxis. As of the data-cutoff date (September 20, 2021), five patients had normal factor IX levels (range, 51 to 78%), three patients had levels from 23 to 43%, and one had a level of 260%. Of the reported adverse events, approximately 10% were related to FLT180a and 24% to immunosuppression. Increases in liver aminotransferase levels were the most common FLT180a-related adverse events. Late increases in aminotransferase levels occurred in patients who had received prolonged tacrolimus beyond the glucocorticoid taper. A serious adverse event of arteriovenous fistula thrombosis occurred in the patient with high factor IX levels. CONCLUSIONS: Sustained factor IX levels in the normal range were observed with low doses of FLT180a but necessitated immunosuppression with glucocorticoids with or without tacrolimus. (Funded by Freeline Therapeutics; ClinicalTrials.gov numbers, NCT03369444 and NCT03641703; EudraCT numbers, 2017-000852-24 and 2017-005080-40.).


Assuntos
Dependovirus , Terapia Genética , Glucocorticoides , Hemofilia B , Dependovirus/genética , Fator IX/análise , Fator IX/genética , Seguimentos , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Vetores Genéticos/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Hemofilia B/genética , Hemofilia B/metabolismo , Hemofilia B/terapia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Transaminases/análise
3.
Haemophilia ; 29(3): 743-752, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36811304

RESUMO

INTRODUCTION: The UK National Haemophilia Database (NHD) collects data from all UK persons with haemophilia A with inhibitors (PwHA-I). It is well-placed to investigate patient selection, clinical outcomes, drug safety and other issues not addressed in clinical trials of emicizumab. AIMS: To determine safety, bleeding outcomes and early effects on joint health of emicizumab prophylaxis in a large, unselected cohort using national registry and patient reported Haemtrack (HT) data between 01 January 2018 and 30 September 2021. METHODS: Prospectively collected bleeding outcomes were analysed in people with ≥6 months emicizumab HT data and compared with previous treatment if available. Change in paired Haemophilia Joint Health Scores (HJHS) were analysed in a subgroup. Adverse events (AEs) reports were collected and adjudicated centrally. RESULTS: This analysis includes 117 PwHA-I. Mean annualised bleeding rate (ABR) was .32 (95% CI, .18; .39) over a median 42 months treatment with emicizumab. Within-person comparison (n = 74) demonstrated an 89% reduction in ABR after switching to emicizumab and an increase in zero treated bleed rate from 45 to 88% (p < .01). In a subgroup of 37 people, total HJHS improved in 36%, remained stable in 46% and deteriorated in 18%, with a median (IQR) within-person change of -2.0 (-9, 1.5) (p = .04). Three arterial thrombotic events were reported, two possibly drug related. Other AEs were generally non-severe and usually limited to early treatment, included cutaneous reactions (3.6%), headaches (1.4%), nausea (2.8%) and arthralgia (1.4%). CONCLUSIONS: Emicizumab prophylaxis is associated with sustained low bleeding rates and was generally well-tolerated in people with haemophilia A and inhibitors.


Assuntos
Anticorpos Biespecíficos , Hemofilia A , Humanos , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Seguimentos , Anticorpos Biespecíficos/efeitos adversos , Hemorragia/complicações , Reino Unido , Fator VIII/uso terapêutico
4.
Platelets ; 34(1): 2264940, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37822056

RESUMO

Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.


What is the context?Multiple myeloma is associated with increased risk of thrombosis, although the potential role of platelets in this has not been evaluated.What is new?We show in this pilot study that multiple myeloma and its precursor states of smoldering myeloma and monoclonal gammopathy of undetermined significance are associated with increased levels of platelet responses. This is further exacerbated by treatment with the immunomodulatory drug lenalidomide.What is the impact?This study suggests that more detailed studies are warranted to explore the mechanisms that cause these effects in a larger population of patients, since this may reveal new approaches to prevent myeloma-associated thrombotic complications.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Trombose , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/complicações , Lenalidomida/farmacologia , Lenalidomida/uso terapêutico , Projetos Piloto , Trombose/complicações , Gamopatia Monoclonal de Significância Indeterminada/complicações
5.
Br J Haematol ; 197(4): 397-406, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35191019

RESUMO

The development of effective and safe treatments has significantly increased the life expectancy of persons with haemophilia (PWH). This has been accompanied by an increase in the comorbidities of ageing including cardiovascular disease, which poses particular challenges due to the opposing risks of bleeding from haemophilia and antithrombotic treatments versus thrombosis. Although mortality secondary to coronary artery disease in PWH is less than in the general population, the rate of atherosclerosis appears similar. The prevalence of atrial fibrillation in PWH and risk of secondary thromboembolic stroke are not well established. PWH can be safely supported through acute coronary interventions but data on the safety and efficacy of long-term antithrombotics are scarce. Increased awareness and research on cardiovascular disease in PWH will be crucial to improve primary prevention, acute management, secondary prevention and to best support ageing PWH.


Assuntos
Doenças Cardiovasculares , Hemofilia A , Envelhecimento , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Comorbidade , Hemofilia A/complicações , Hemofilia A/epidemiologia , Hemofilia A/genética , Humanos , Longevidade/genética
6.
Br J Haematol ; 193(2): 397-400, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33715149

RESUMO

This retrospective cohort study investigated the association between factor 8 (F8) genotype severity and factor VIII (FVIII) levels during pregnancy for 52 women (64 pregnancies) who were heterozygous carriers of mild, moderate or severe haemophilia A. There were no significant differences in FVIII levels for carriers of mild, moderate or severe haemophilia A at baseline [mean (SD) level: mild, 0·78 (0·22); moderate, 0·83 (0·33); severe, 0·70 (0·25) iu/ml; P = 0·81] or in the third trimester [mean (SD) level: mild, 1·42 (0·28); moderate, 1·47 (0·41); severe, 1·37 (0·49) iu/ml; P = 0·80). Post-partum haemorrhage rates were higher for carriers of severe haemophilia A (13/24; 54·2%) compared to carriers of mild haemophilia A (four of 14; 28·6%).


Assuntos
Fator VIII/genética , Hemofilia A/genética , Hemorragia Pós-Parto/genética , Terceiro Trimestre da Gravidez/sangue , Adolescente , Adulto , Fator VIII/análise , Feminino , Genótipo , Hemofilia A/complicações , Hemofilia A/diagnóstico , Heterozigoto , Humanos , Incidência , Mutação , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Gravidez , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
7.
J Nurs Care Qual ; 36(3): 217-222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33259466

RESUMO

BACKGROUND: Nursing policies and protocols exist to promote high-quality, safe, and effective nursing practice; however, there is little evidence demonstrating how nurses actually use them to inform their everyday, routine practice. PURPOSE: The purposes were to explore the extent to which nurses use nursing policies and protocols to guide their routine practice, and identify barriers and facilitators affecting the frequency with which nurses use nursing policies and protocols. METHODS: Licensed nurses (N = 235) providing direct care to inpatients and outpatients in a large medical center participated in an 18-question online survey. RESULTS: Most nurses access policies and protocols once a month or more; the greatest barrier to more frequent access was length of the policy or protocol. CONCLUSIONS: Organizations should make policies and protocols succinct, current, and easily accessible. Studies are needed to determine how policies and procedures can best meet the needs of stakeholders, including health care organizations, staff, and patients.


Assuntos
Hospitais , Enfermeiras e Enfermeiros , Humanos , Pacientes Internados , Políticas , Inquéritos e Questionários
8.
Haemophilia ; 26(2): 278-281, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32083769

RESUMO

INTRODUCTION: Extended half-life factor IX concentrates (EHL-FIX) can be administered weekly to prevent bleeding for persons with severe haemophilia B. We report the experience of a large UK haemophilia comprehensive care centre using low dose EHL-FIX for persons with severe haemophilia B. AIM: The low doses used in real world are approximately half of the doses used in clinical trials. We aim to assess the efficacy and safety of low dose EHL-FIX. METHODS: Data from a cohort of 13 patients who were switched from standard half-life factor IX (SHL-FIX) to Alprolix® (mean dose 31.5 IU/kg) and seven patients who switched from standard half-life factor IX to Idelvion® (mean dose 20.2 IU/kg) were included. RESULTS: The median annualized bleeding rate was similar for SHL-FIX (median 3, interquartile range [IQR] 1-5) and EHL-FIX (median 3, IQR 1-5.25). Quality of life scores, measured using the European Quality of Life 5 Dimensions assessment were similar for SHL-FIX (median 0.76, IQR: 0.63-0.84) and EHL-FIX (median 0.79, IQR: 0.58-0.88). CONCLUSION: This study shows that EHL-FIX given at low doses can be effective for prevention of bleeding for persons with severe haemophilia B.


Assuntos
Fator IX/uso terapêutico , Hemofilia B/tratamento farmacológico , Qualidade de Vida/psicologia , Adolescente , Adulto , Fator IX/farmacologia , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
Crit Care ; 24(1): 561, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948243

RESUMO

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.


Assuntos
Infecções por Coronavirus/complicações , Estado Terminal , Hemorragia/etiologia , Pneumonia Viral/complicações , Trombose/etiologia , Betacoronavirus , COVID-19 , Infecções por Coronavirus/terapia , Feminino , Hemorragia/terapia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , SARS-CoV-2 , Tromboelastografia , Trombose/terapia , Reino Unido
10.
Br J Haematol ; 184(5): 712-720, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30592034

RESUMO

Advances in the development of effective and safe treatments for haemophilia over the last 50 years have resulted in a significant increase in the life expectancy of persons with haemophilia (PWH). The management of this new cohort of middle-aged and elderly PWH is challenging because of the opposing risks of haemophilia and age-related cardiovascular disease and malignancy. Furthermore, this cohort of ageing PWH has the additional comorbidities of human immunodeficiency virus/hepatitis C and chronic haemophilic arthropathy. This article reviews the prevalence, underlying mechanisms and treatment strategies for managing these comorbidities. International collaboration is essential for registry data and further prospective trials to inform optimal evidence-based management for this rare disorder in the future.


Assuntos
Envelhecimento , Doenças Cardiovasculares/terapia , Infecções por HIV/terapia , Hemofilia A/terapia , Hepatite C/terapia , Neoplasias/terapia , Idoso , Idoso de 80 Anos ou mais , HIV-1 , Humanos , Pessoa de Meia-Idade
11.
BMC Pregnancy Childbirth ; 19(1): 364, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638940

RESUMO

BACKGROUND: In population level studies, the conventional practice of categorizing women into low and high maternal risk samples relies upon ascertaining the presence of various comorbid conditions in administrative data. Two problems with the conventional method include variability in the recommended comorbidities to consider and inability to distinguish between maternal and fetal risks. High maternal risk sample selection may be improved by using the Obstetric Comorbidity Index (OCI), a system of risk scoring based on weighting comorbidities associated with maternal end organ damage. The purpose of this study was to compare the net benefit of using OCI risk scoring vs the conventional risk identification method to identify a sample of women at high maternal risk in administrative data. METHODS: This was a net benefit analysis using linked delivery hospitalization discharge and vital records data for women experiencing singleton births in Georgia from 2008 to 2012. We compared the value identifying a sample of women at high maternal risk using the OCI score to the conventional method of dichotomous identification of any comorbidities. Value was measured by the ability to select a sample of women designated as high maternal risk who experienced severe maternal morbidity or mortality. RESULTS: The high maternal risk sample created with the OCI had a small but positive net benefit (+ 0.6), while the conventionally derived sample had a negative net benefit indicating the sample selection performed worse than identifying no woman as high maternal risk. CONCLUSIONS: The OCI can be used to select women at high maternal risk in administrative data. The OCI provides a consistent method of identification for women at risk of maternal morbidity and mortality and avoids confounding all obstetric risk factors with specific maternal risk factors. Using the OCI may help reduce misclassification as high maternal risk and improve the consistency in identifying women at high maternal risk in administrative data.


Assuntos
Hospitalização/estatística & dados numéricos , Saúde Materna/estatística & dados numéricos , Mães/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Adulto , Comorbidade , Bases de Dados Factuais , Feminino , Seguimentos , Georgia/epidemiologia , Humanos , Idade Materna , Gravidez , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
13.
J Nurs Care Qual ; 33(2): 157-165, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28658191

RESUMO

This study explored the trajectory of patients who remained on a general unit after medical emergency team activation. Of those who had a second activation within 24 hours, 80% occurred within 12 hours of the baseline activation. Chest pain and recent intensive care unit discharge were associated with having a second activation. There were statistically, not clinically, significant associations between mean vital signs and second activations; however, the patterns of change may be clinically useful.


Assuntos
Equipe de Respostas Rápidas de Hospitais , Unidades de Terapia Intensiva , Admissão do Paciente , Dor no Peito/etiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Estudos Longitudinais , Masculino , Alta do Paciente , Estudos Prospectivos , Fatores de Tempo , Sinais Vitais/fisiologia
14.
Nurs Adm Q ; 42(4): 331-342, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30180079

RESUMO

Schools of nursing located within academic health centers have embraced expanded opportunities to lead in this era of rapid change and considerable uncertainty in US health care. These schools bear a unique responsibility to work with their clinical nursing partners to advance the care of patients, improve the health of communities and populations, and help steward the nation's health care resources. This article describes how the Emory University Nell Hodgson Woodruff School of Nursing has formed and sustained academic-practice partnerships in response to these imperatives. The structures and processes that have supported the partnerships are shared, as are the keys to success in a true partnership. The authors describe the work required to achieve mutually agreed-upon goals, along with the challenges that faculty and health care leaders have faced in their journey to system partnerships.


Assuntos
Centros Médicos Acadêmicos/métodos , Comportamento Cooperativo , Gerenciamento da Prática Profissional/tendências , Escolas de Enfermagem/tendências , Centros Médicos Acadêmicos/organização & administração , Humanos
16.
Nurs Adm Q ; 40(1): 14-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26636230

RESUMO

Accountable Care Units are a disruptive innovation that has moved care on acute care units from a traditional silo model, in which each discipline works separately from all others, to one in which multiple disciplines work together with patients and their families to move patients safely through their hospital stay. This article describes the "what," "how," and "why" of the Accountable Care Units model as it has evolved in different locations across a single health system and includes the lessons learned as different units and hospitals continue working to implement the model in their complex care environments.


Assuntos
Organizações de Assistência Responsáveis/organização & administração , Difusão de Inovações , Modelos Organizacionais , Enfermeiros Administradores , Humanos , Estados Unidos
19.
JAMA ; 323(19): 1975-1976, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427298
20.
J Health Polit Policy Law ; 40(3): 487-530, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25700372

RESUMO

Resolution of long-standing debates about the role and impact of advance directives - living wills and powers of attorney for health care - has been hampered by a dearth of appropriate data, in particular data that compare the process and outcomes of end-of-life decision making on behalf of patients with and without advance directives. Drawing on a large ethnographic study of patients in two intensive care units in a large urban teaching hospital, this article compares aspects of the medical decision-making process and outcomes by advance-directive status. Controlling for demographic characteristics and severity of illness, the study finds few significant differences between patients without advance directives and those who claim to have them. Surprisingly, these few differences hold only for those whose directives are in their hospital chart. There are no significant differences between those with no directive and those claiming to have a copy at home or elsewhere. The article considers the implications if directives seemingly must be in hand to show even modest effects. Do advance directives direct? The intensive care unit data provide far more support for the growing body of literature that casts doubt on their impact than studies that promote the use of them.


Assuntos
Diretivas Antecipadas/psicologia , Diretivas Antecipadas/estatística & dados numéricos , Tomada de Decisões , Unidades de Terapia Intensiva , Adulto , Diretivas Antecipadas/etnologia , Fatores Etários , Idoso , Antropologia Cultural , Atitude , Feminino , Hospitais de Ensino , Hospitais Urbanos , Humanos , Masculino , Pessoa de Meia-Idade , Autonomia Pessoal , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores Socioeconômicos , Assistência Terminal , Consentimento do Representante Legal
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