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1.
Omega (Westport) ; : 302228221116513, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35857485

RESUMO

The life-limiting and unpredictable nature of sickle cell disease (SCD) is well-established, yet there is limited literature on end-of-life planning. The purpose of this study was to describe perspectives about preparing for death for older adults with SCD. We enrolled 19 older adults with SCD (age ≥ 50 years) into this qualitative descriptive study. Theme 1 was "anticipation of early death," with sub-themes: (a) informed of early death and (b) making plans for death. Theme 2 was "near death experiences." Theme 3 was "differences in level of comfort with death" with subthemes: (a) death as a part of life and (b) differences in level of comfort discussing death. Theme 4 was "influence of spirituality" with subthemes: (a) God controls the timing of death and (b) belief in the afterlife. These results will inform interventions to improve the quality of patient-provider communication to provide goal-concordant end-of-life care for adults with SCD.

2.
Pediatr Blood Cancer ; 68(8): e29066, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33855784

RESUMO

BACKGROUND: Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)-identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts. METHODS: We conducted a retrospective study of patients ≤18 years old consecutively diagnosed with SAA between 2000 and 2018. Patients received either standard immunosuppressive therapy (IST-Std) or IST with eltrombopag (IST-Epag). The primary outcome was the objective response (OR), including partial and complete response (CR), at 6 and 12 months after starting therapy. RESULTS: We identified 16 patients receiving IST-Std and nine IST-Epag treatment (seven of nine as upfront therapy and two of seven after previously failed IST). The OR at 6 and 12 months in IST-Std arm was 71% and 100%, with CR in 29% and 58%, respectively. Seven patients receiving upfront IST-Epag had OR at 6 and 12 months, with two of seven (29%) achieving CR at 6 and 12 months. Two patients who previously failed standard IST did not respond to eltrombopag. No significant differences were observed in both cohorts with regard to infections. One IST-Epag-treated patient developed transient grade 3 transaminitis. Finally, no changes in paroxysmal nocturnal hemoglobinuria (PNH) clone size and cytogenetic abnormalities were seen in either cohort. CONCLUSION: The addition of eltrombopag to standard IST was well tolerated and resulted in satisfactory hematological response at 6 and 12 months in this single-institution experience. A larger cohort with longer follow-up is required to assess response durability.


Assuntos
Anemia Aplástica , Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Imunossupressores/uso terapêutico , Pirazóis/uso terapêutico , Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário , Criança , Ciclosporina , Humanos , Estudos Retrospectivos , Resultado do Tratamento
4.
Lit Med ; 42(1): 39-51, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39219520
5.
Eur J Neurosci ; 43(9): 1190-202, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26833814

RESUMO

Brain reward circuits are implicated in stress-related psychiatric disorders. Exercise reduces the incidence of stress-related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise-induced stress resistance is independent of exercise controllability; both voluntary running (VR) and forced running (FR) protect rats against the anxiety-like and depression-like behavioural consequences of stress. Voluntary exercise is a natural reward, but whether rats find FR rewarding is unknown. Moreover, the contribution of dopamine (DA) and striatal reward circuits to exercise reward is not well characterized. Adult, male rats were assigned to locked wheels, VR, or FR groups. FR rats were forced to run in a pattern resembling the natural wheel running behavior of rats. Both VR and FR increased the reward-related plasticity marker ΔFosB in the dorsal striatum and nucleus accumbens, and increased the activity of DA neurons in the lateral ventral tegmental area, as revealed by immunohistochemistry for tyrosine hydroxylase and pCREB. Both VR and FR rats developed conditioned place preference (CPP) to the side of a CPP chamber paired with exercise. Re-exposure to the exercise-paired side of the CPP chamber elicited conditioned increases in cfos mRNA in direct-pathway (dynorphin-positive) neurons in the dorsal striatum and nucleus accumbens in both VR and FR rats, and in tyrosine hydroxylase-positive neurons in the lateral ventral tegmental area of VR rats only. The results suggest that the rewarding effects of exercise are independent of exercise controllability and provide insight into the DA and striatal circuitries involved in exercise reward and exercise-induced stress resistance.


Assuntos
Condicionamento Físico Animal , Recompensa , Estresse Psicológico/fisiopatologia , Animais , Corpo Estriado/citologia , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/fisiologia , Masculino , Plasticidade Neuronal , Núcleo Accumbens/citologia , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Endogâmicos F344 , Corrida , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
6.
7.
Ann Intern Med ; 165(3): W5, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27479228
8.
Ann Intern Med ; 164(7): W12, 2016 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-27043993
9.
J Palliat Med ; 25(2): 307-311, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34788574

RESUMO

Background: National Consensus Project for quality palliative care guidelines emphasizes the importance of a comprehensive assessment of all care domains, including physical, psychosocial, and spiritual aspects of care, for seriously ill patients. However, less is known about how real-world practice compares with this guideline. Objective: To describe clinicians' assessment practices and factors influencing their approach. Design: This is a two-part web-based survey of palliative care clinicians from five academic groups in the United States. Results: Nineteen out of 25 invited clinicians (physicians, nurse practitioners, and physician assistants) completed the survey. A majority (62%) reported that, although some elements of assessment were mandatory, their usual practice was to tailor the focus of the consultation. Time limitations and workload received the highest mean scores as reasons for tailored assessment (6.1 on a 0-9 importance scale), followed by beliefs that comprehensive assessment is unnecessary (4.8) and absence of the full interdisciplinary team (4.4). All participants cited symptom acuity, and 91% cited reason for consult as factors influencing a tailored approach. Among domains "always" assessed, physical symptoms were reported most commonly (81%) and spiritual and cultural factors least commonly (24% and 19%, respectively). Although a majority of clinicians reported usually tailoring their consultations, mean importance scores for almost all assessment elements were high (range 3.9-8.8, mean 7.1); however, there was some variation based on reason for consult. Spiritual elements received lower importance scores relative to other elements (5.0 vs. 7.4 mean score for all others). Conclusion: Although clinicians placed high importance on most elements included in comprehensive palliative care, in practice they often tailored their consultations, and the perceived relative importance of domains shifted depending upon the type of consultation.


Assuntos
Profissionais de Enfermagem , Cuidados Paliativos , Humanos , Qualidade da Assistência à Saúde , Encaminhamento e Consulta , Espiritualidade , Inquéritos e Questionários , Estados Unidos
10.
Am J Gastroenterol ; 106(11): 1899-908; quiz 1909, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21826111

RESUMO

OBJECTIVES: Endoscopic ablation of Barrett's esophagus can bury metaplastic glands under a layer of neosquamous epithelium. To explore the frequency and importance of buried metaplasia, we have conducted a systematic review of reports on endoscopic ablation. METHODS: We performed computerized and manual searches for articles on the results of photodynamic therapy (PDT) and radiofrequency ablation (RFA) for Barrett's esophagus. We extracted information on the number of patients treated, biopsy protocol, biopsy depth, and frequency of buried metaplasia. RESULTS: We found 9 articles describing 34 patients with neoplasia appearing in buried metaplasia (31 after PDT). We found five articles describing a baseline prevalence of buried metaplasia (before ablation) ranging from 0% to 28%. In 22 reports on PDT for 953 patients, buried metaplasia was found in 135 (14.2%); in 18 reports on RFA for 1,004 patients, buried metaplasia was found in only 9 (0.9%). A major problem limiting the conclusions that can be drawn from these reports is that they do not describe specifically how frequently biopsy specimens contained sufficient subepithelial lamina propria to be informative for buried metaplasia. CONCLUSIONS: Endoscopic ablation can bury metaplastic glands with neoplastic potential but, even without ablation, buried metaplasia often is found in areas where Barrett's epithelium abuts squamous epithelium. Buried metaplasia is reported less frequently after RFA than after PDT. However, available reports do not provide crucial information on the adequacy of biopsy specimens and, therefore, the frequency and importance of buried metaplasia after endoscopic ablation remain unclear.


Assuntos
Adenocarcinoma/patologia , Esôfago de Barrett/tratamento farmacológico , Esôfago de Barrett/cirurgia , Ablação por Cateter/efeitos adversos , Neoplasias Esofágicas/patologia , Fotoquimioterapia/efeitos adversos , Adenocarcinoma/diagnóstico , Esôfago de Barrett/patologia , Neoplasias Esofágicas/diagnóstico , Esofagoscopia , Humanos , Metaplasia
11.
J Palliat Med ; 24(8): 1167-1173, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33351728

RESUMO

Objectives: To characterize clinician experiences of hospice access and scope of services for undocumented immigrants. Background: The 10.5 million undocumented immigrants in the United States are not covered by Medicare's hospice benefit and are at high risk for being uninsured. Limited data are available regarding hospice services for this population. Setting/Subjects: Two hundred ninety-four interdisciplinary palliative care clinicians from across the United States. Measurements: Participants completed a web-based survey regarding hospice access and scope of services for undocumented immigrants in their location. We used simple frequencies to report clinician responses and chi-square analysis to evaluate associations between response and location. We performed rapid qualitative analysis of free-text responses to identify common limitations in scope of services. Results: A majority of clinicians (68%) perceived that access to hospice was limited or unavailable for undocumented immigrants in their location, and among respondents who provided data regarding hospice scope, 38% reported that services provided to undocumented immigrants were limited compared to those provided to other patients. Reports of restricted access and scope varied by region, and those in large metropolitan areas were more likely to report restricted scope of care than those in smaller towns (43% vs. 28%; p = 0.03). In our qualitative analysis of free-text responses, common limitations in hospice scope included reduced access to medications and equipment, inability to access inpatient hospice, inadequate translation services, reduced staffing, and restricted duration of services. Conclusions: Undocumented immigrants may face barriers in accessing comprehensive hospice services. Public policy changes that improve access to hospice may improve end-of-life care for undocumented immigrants.


Assuntos
Emigrantes e Imigrantes , Hospitais para Doentes Terminais , Imigrantes Indocumentados , Idoso , Acessibilidade aos Serviços de Saúde , Humanos , Medicare , Inquéritos e Questionários , Estados Unidos
13.
AMA J Ethics ; 20(8): E778-779, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30118430

RESUMO

In this graphic narrative, a clinician illustrates an experience of caring for an undocumented patient suffering from end-stage renal disease (ESRD). Cruel Carousel tells one of the stories that most profoundly shaped the author's own views on health care for undocumented immigrants. Graphic narrative was chosen to tell this story because words alone couldn't capture the patient's experience or the author's distress about what happened to him.


Assuntos
Emigrantes e Imigrantes/psicologia , Empatia , Romances Gráficos como Assunto , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Diálise Renal/ética , Diálise Renal/psicologia , Adulto , Evolução Fatal , Humanos , Masculino , México , Estados Unidos
14.
Mol Cell Endocrinol ; 478: 97-105, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30063946

RESUMO

Obesity is a risk factor for infertility, but mechanisms underlying this risk are unclear. Fertility is regulated by hypothalamic gonadotropin-releasing hormone, encoded by the Gnrh1 gene. Because obesity promotes endoplasmic reticulum (ER) stress, we sought to determine how tunicamycin-induced ER stress affected Gnrh1 gene expression in the mouse hypothalamic cell line GT1-7. Tunicamycin repressed expression of Gnrh1 in a PKC- and JNK-dependent manner, while upregulating expression of a known Gnrh1 repressor, Fos. Obesity is associated with increased circulating free fatty acids, and exposure to palmitate promoted ER stress and inflammation. Fos expression increased with palmitate dose, but Gnrh1 expression was upregulated with low-dose palmitate and repressed with high-dose palmitate. Using a small molecule inhibitor, we determined that AP-1 was required for Gnrh1 repression by high-dose palmitate or tunicamycin-induced ER stress. These findings suggest that hypogonadism driven by decreased hypothalamic GnRH may be a component of obesity-related infertility.


Assuntos
Regulação da Expressão Gênica , Hormônio Liberador de Gonadotropina/genética , Obesidade/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Estresse Fisiológico , Fator de Transcrição AP-1/metabolismo , Animais , Linhagem Celular , Estresse do Retículo Endoplasmático/genética , Hormônio Liberador de Gonadotropina/metabolismo , Inflamação/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Ácido Palmítico , Proteína Quinase C/metabolismo , Proteínas Repressoras/metabolismo , Estresse Fisiológico/genética , Resposta a Proteínas não Dobradas/genética
15.
Neuropsychopharmacology ; 43(3): 665-672, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28976945

RESUMO

Manipulations that increase dopamine (DA) signaling can enhance fear extinction, but the circuits involved remain unknown. DA neurons originating in the substantia nigra (SN) projecting to the dorsal striatum (DS) are traditionally viewed in the context of motor behavior, but growing data implicate this nigrostriatal circuit in emotion. Here we investigated the role of nigrostriatal DA in fear extinction. Activation of SN DA neurons with designer Gq-coupled receptors exclusively activated by designer drugs (Gq-DREADD) during fear extinction had no effect on fear extinction acquisition, but enhanced fear extinction memory and blocked the renewal of fear in a novel context; a pattern of data paralleled by cFos expression in the central amygdala. D1 receptors in the DS are a likely target mediating the effects of SN DA activation. D1-expressing neurons in the medial DS (DMS) were recruited during fear extinction, and Gq-DREADD-induced DA potentiated activity of D1-expressing neurons in both the DMS and the lateral DS (DLS). Pharmacological activation of D1 receptors in the DS did not impact fear extinction acquisition or memory, but blocked fear renewal in a novel context. These data suggest that activation of SN DA neurons and DS D1 receptors during fear extinction render fear extinction memory resistant to the disrupting effects of changes in contextual contingencies, perhaps by recruiting habitual learning strategies involving the DLS. Nigrostriatal DA thus represents a novel target to enhance long-term efficacy of extinction-based therapies for anxiety and trauma-related disorders.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Substância Negra/fisiologia , Animais , Percepção Auditiva/efeitos dos fármacos , Percepção Auditiva/fisiologia , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Núcleo Accumbens/citologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismo , Ratos Long-Evans , Ratos Transgênicos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Substância Negra/citologia , Substância Negra/efeitos dos fármacos
18.
J Palliat Med ; 19(5): 559-65, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27046735

RESUMO

BACKGROUND/OBJECTIVE: The goal of this update in hospice and palliative care is to summarize and critique research published between January 1 and December 31, 2014 that has a high potential for impact on clinical practice. DESIGN: To identify articles we hand searched 22 leading journals, the Cochrane Database of Systematic Reviews, and Fast Article Critical Summaries for Clinicians in Palliative Care. We also performed a PubMed keyword search using the terms "hospice" and "palliative care." MEASUREMENTS: We ranked candidate articles based on study quality, appeal to a breadth of palliative care clinicians, and potential for impact on clinical practice. RESULTS: In this manuscript we have summarized the findings of eight articles with the highest ratings and make recommendations for clinical practice based on the strength of the resulting evidence.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Hospitais para Doentes Terminais
19.
BMJ ; 370: m2630, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651171
20.
BMJ ; 370: m3005, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32819922
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