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We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.
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Antivirais/química , Tratamento Farmacológico da COVID-19 , SARS-CoV-2/efeitos dos fármacos , Proteínas não Estruturais Virais/química , Inteligência Artificial , Sítios de Ligação , Simulação por Computador , Bases de Dados de Compostos Químicos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Simulação de Acoplamento Molecular , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Relação Estrutura-AtividadeRESUMO
HIV and sexuality stigma impede HIV prevention and care efforts. HealthMpowerment.org (HMP) is an interactive mobile phone- and web-based HIV prevention and care intervention for young Black men who have sex with men (YBMSM; ages 18-30) in the United States. HMP included three forums where participants could share their experiences. In this study, we explored whether engaging in stigma-related discussions was associated with changes in YBMSM's stigma-related scores throughout the trial. YBMSM (ages 18-30; N = 238) participating in HMP completed surveys at baseline, and 3 and 6 month follow-ups that included a series of scales focused on HIV and sexuality (internalized homophobia; sexual prejudice) stigma. Sixty-two participants contributed to the forums (1497 posts). We coded instances where YBMSM's conversations were stigma related (915 posts, 61.1%), including discussions of anticipated (74/915, 8.1%), experienced (125/915, 13.7%), internalized (410/915, 44.8%), and/or challenged (639/915, 69.8%) stigma regarding sexuality and HIV. Using a mixed methods approach, we examined whether changes in YBMSM's stigma scores were associated with stigma-related discussions within the forum. We controlled for age, HIV status, income, and educational attainment in these multivariable models. YBMSM who discussed experiencing HIV stigma in the forums reported decreases in perceived HIV stigma over time (b = - 0.37, p ≤ 0.05). YBMSM whose forum posts indicated anticipated HIV stigma reported increases in HIV stigma over time (b = 0.46, p ≤ 0.01). Participants who challenged sexuality-related stigma in forums had lower internalized homophobia (b = - 0.68, p ≤ 0.01) at baseline. YBMSM whose discussions focused on experiencing sexuality-related stigma reported increases in internalized homophobia (b = 0.39, p ≤ 0.01) and sexual prejudice (b = 0.87, p ≤ 0.05) over time. Developing strategies to combat stigma remains a key priority. HMP created an online space where YBMSM could discuss HIV and sexuality stigma. Although a limited number of HMP participants authored the majority of these forum discussions, the discussions were associated with changes in the sample's stigma scores over time. Online interventions (e.g., social media, apps) should consider the inclusion of forums to address stigma and test the efficacy of forums to improve YBMSM's HIV prevention and care continuum outcomes.
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Negro ou Afro-Americano/psicologia , Infecções por HIV/psicologia , Homofobia , Homossexualidade Masculina/psicologia , Estigma Social , Telemedicina , Adolescente , Adulto , Telefone Celular , Continuidade da Assistência ao Paciente , Infecções por HIV/etnologia , Homofobia/etnologia , Homofobia/psicologia , Homossexualidade Masculina/etnologia , Humanos , Masculino , Comportamento Sexual , Minorias Sexuais e de Gênero , Inquéritos e Questionários , Estados Unidos , Adulto JovemRESUMO
We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.
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PURPOSE: To determine the incidence of myelodysplasia (MDS) and/or acute leukemia (AL) in breast cancer patients after high-dose chemotherapy (HDC) with a single conditioning regimen and autologous bone marrow transplant (ABMT), and analyze the cytogenetic abnormalities that arise after HDC. PATIENTS AND METHODS: We retrospectively reviewed the records of 864 breast cancer patients who underwent ABMT at Duke University Medical Center, Durham, NC, from 1985 through 1996 who received the same preparative regimen of cyclophosphamide 1,875 mg/m2 for 3 days, cisplatin 55 mg/m2 for 3 days, and BCNU 600 mg/m2 for 1 day (CPB). Pretransplant cytogenetics were analyzed in all patients and posttransplant cytogenetics were evaluated in four of five patients who developed MDS/AL. RESULTS: Five of 864 patients developed MDS/AL after HDC with CPB and ABMT. The crude cumulative incidence of MDS/AL was 0.58%. The Kaplan-Meier curve shows a 4-year probability of developing MDS/AL of 1.6%. Pretransplant cytogenetics performed on these five patients were all normal. Posttransplant cytogenetics were performed on four of five patients and they were abnormal in all four, although only one patient had the most common cytogenetic abnormality associated with secondary MDS/AL (chromosome 5 and/or 7 abnormality). CONCLUSION: Whereas MDS/AL is a potential complication of HDC with CPB and ABMT, the incidence in this series of patients with breast cancer was relatively low compared with that reported in patients with non-Hodgkin's lymphoma who underwent ABMT. The cytogenetic abnormalities reported in this group of breast cancer patients were not typical of those seen in prior reports of secondary MDS/AL and appear to have occurred after HDC.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Neoplasias da Mama/terapia , Leucemia/etiologia , Síndromes Mielodisplásicas/etiologia , Doença Aguda , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/administração & dosagem , Aberrações Cromossômicas , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Cariotipagem , Leucemia/genética , Síndromes Mielodisplásicas/genética , Estudos Retrospectivos , Análise de Sobrevida , Transplante AutólogoRESUMO
INTRODUCTION: Despite the improvement of diagnostic methods and chemotherapeutic regimens in breast cancer, overall 5-year survival significantly depends on the stage of the disease. Over expression of tumor suppressor gene p53 and the marker for cellular proliferation Ki67 in breast cancer may have prognostic significance. METHODS: We evaluated 675 patients diagnosed with breast cancer at UF Health Jacksonville between January 2000 and June 2007 with up to 5-year follow up. The aim of the study was to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 may predict outcome, the 'hazard' of dying. Cox's proportional hazards models were used to control for age (< 50 vs. ≥ 50), race (white vs. other), lymph node group (negative vs. positive), ER (estrogen receptor) group (negative vs. positive), PR (progesterone receptor) group (negative vs. positive), and tumor type. RESULTS: When only p53 was considered in the model, the hazard of dying was significantly higher for p53 positive compared to p53 negative (HR = 1.32, 95% CI 1.02, 1.70, p = 0.036). When only ki67 was considered in the model, the hazard of dying was significantly higher for ki67 positive compared to ki67 negative (Hazard ratio = 1.64, 95% CI 1.08, 2.49, p = 0.021). Neither of the two markers, nor their interaction was significant when all variables were considered in the model. DISCUSSION: This study confirms the expression of p53 and Ki67 as strong individual indicators of patient outcome. However, when controlling for the other variables, the two markers are not independent predictors. Future studies that will include these markers might help design targeted therapy.
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Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Antígeno Ki-67/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma/mortalidade , Carcinoma/terapia , Feminino , Florida/epidemiologia , Seguimentos , Humanos , Pessoa de Meia-Idade , Medicina de Precisão , Estudos RetrospectivosRESUMO
While much attention has been devoted to cytotoxic drugs and radiation therapy in the pregnant cancer patient, the drugs used for management of symptoms and complications related to cancer during pregnancy have been overlooked. There is substantial overlap between the symptoms of cancer and cancer management and the symptoms related to pregnancy. The mainstay of symptom management is drug therapy and the potential for a drug to be embryotoxic or teratogenic depends on when it is given. In general, drugs not proven safe in pregnancy should be withheld, especially during the first trimester. The few drugs that have been proven to be teratogenic are alcohol, thalidomide, the folic acid antagonists (which includes methotrexate), diethylstilbestrol, and the vitamin A isomers, but there is a good deal of uncertainty about many other therapeutic agents. Placental transport of drugs from mother to fetus must be taken into consideration from the fifth week of gestation to parturition. Although the first trimester is the time of most organ development in the fetus, the brain continues to develop throughout pregnancy and may be damaged later in pregnancy, resulting in diminished intelligence or behavioral problems. This review will focus on the treatment of the most common symptoms of cancer in a pregnant patient and the potential for fetal damage.
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Cuidados Paliativos , Preparações Farmacêuticas , Complicações Neoplásicas na Gravidez , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/fisiopatologia , Estados Unidos , United States Food and Drug AdministrationRESUMO
Complications due to cancer and its treatment are common and increase in incidence and severity as the disease progresses. Central nervous system complications affect 15% to 20% of patients, and up to 75% have bone metastases at some point during the disease process. Endocrine abnormalities include hypercalcemia, adrenal insufficiency, and inappropriate antidiuretic syndrome. Hematologic disorders, malignant effusions, and gastrointestinal (GI) problems may cause significant morbidity.
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Neoplasias/complicações , Neoplasias/terapia , Cuidados Paliativos , Progressão da Doença , Doenças do Sistema Endócrino/etiologia , Doenças do Sistema Endócrino/terapia , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Doenças Hematológicas/etiologia , Doenças Hematológicas/terapia , Humanos , Doenças Musculares/etiologia , Doenças Musculares/terapia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Doenças Vasculares/etiologia , Doenças Vasculares/terapiaRESUMO
There has been growing interest in the United States in postgraduate training in palliative medicine. In order for this to proceed in an organized fashion, educational standards need to be developed. We must define what our knowledge base is and what we require of a specialty-trained individual. This article reports the development of the first fellowship program in the United States, with the goal of encouraging further discussion and ultimately obtaining specialty recognition.
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Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Cuidados Paliativos , Desenvolvimento de Programas , Definição da Elegibilidade , Objetivos , Humanos , Pesquisa , Estados UnidosRESUMO
A method is presented for radioimmunological determination of 3alpha, 5beta-tetrahydroaldosterone. It is based upon the reactivity of this steroid with an antiserum induced by the 3-carboxymethyloxime of 18, 21-aldosterone diacetate conjugated with bovine serum albumin. One hundred microliters of urine enzymatically hydrolyzed with an helix pomatia preparation, containing tritiated tetrahydroaldosterone for the yield calculation, were extracted with dichloromethane and chromatographed on a small celite column. The yield after extraction and chromatography was 64 +/- 17%. The radioimmunological determination was carried out in a conventional manner. The method is specific, sensitive (10 pg/tube), exact, reproducible, very simple and extremely rapid. The results showed good agreement with values given by a colorimetric method (p less than 0.001). The median value measured in 45 healthy adult subjects under standard sodium diet was 53.3 microgram/24h (95 % of the population within a 16.6 to 131.1 microgram/24h range). In 78 cases of adrenocortical insufficiency, 60 cases of obesity and 28 cases of hypokalemia, the median values (and the ranges : microgram/24h) were respectively 7.7 (1.0 - 51.0), 80.9 (17.0 - 503.0) and 64.3 (8.0 - 181.0). In 330 hypertensive patients the excretion of tetrahydroaldosterone exceeded the normal range in 115 cases (35%) with a median of 199.7 microgram/24h (131 to 620 microgram/24h).
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Aldosterona/análogos & derivados , Aldosterona/imunologia , Aldosterona/urina , Reações Cruzadas , Humanos , Oximas , Radioimunoensaio/métodosRESUMO
The vascular endothelium is a biologically active monolayer of cells provided an interface between blood and tissues. Vascular endothelial cells (ECs) have two functional states, which are allowed by their different properties: (i) vaso regulating properties: ECs releases vasomotor components, as endothelin (vaso constriction), prostacyclin and nitrite oxide (vaso dilatation); (ii) antithrombotic and hemostatic properties; and (iii) anti-adhesion properties. The endothelium is normally antithrombotic and anti-adhesive to ensure blood fluidity. During many cardio-vascular diseases, these properties may be reversed. Thus, the ECs have a determinant role in hemodynamic control through these various metabolic activities. Otherwise, many studies have demonstrated that local blood flow conditions have a crucial role on the EC properties (mechanotransduction concept). The knowledge of the properties of ECs and the control of the phenomena which define their functions is a key element in the cardiovascular diseases understanding.
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Fenômenos Fisiológicos Sanguíneos , Endotélio Vascular/fisiologia , Hemorreologia , Animais , HumanosRESUMO
The adhesion of polymorphonuclear leukocytes (PMNs) on the vascular endothelium is a complex process that occurs during biological and pathological events and involves a large family of molecules. This phenomenom could be approached by a modelisation study of the adhesion of PMNs on a biological substrate, fibrinogen. Two different physiological conditions were tested such as the activated state of PMNs with a synthetic pro-inflammatory activator (N-Formyl-Methionyl-Leucyl-Phenylalanine, FMLP). The activated state of PMNs was both quantified by flow cytometry and controlled by fluorescence microscopy. The results suggest that quiescent PMNs deposit in accordance with the ballistic deposition model. The preliminary results obtained with FMLP-stimulated PMNs show a different deposit process compared to quiescent PMNs but do not allow to determine exactly a deposition model.
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Fibrinogênio/metabolismo , Leucócitos/fisiologia , Modelos Biológicos , Molécula de Adesão de Leucócito Ativado/análise , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Fibrinogênio/farmacologia , Citometria de Fluxo , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Microscopia de Fluorescência , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Propriedades de Superfície/efeitos dos fármacosRESUMO
Plasma concentrations of atrial natriuretic factor (ANF), catecholamines (adrenaline, noradrenaline, dopamine) and aldosterone, and plasma renin activity (PRA) were measured in a group of 20 patients with moderate to medium heart failure (NYHA class II 7 patients, class III 13 patients), 24 hours after treatment was discontinued. Compared with a control group, plasma concentrations of ANF (p less than 0.01), noradrenaline (p less than 0.05), aldosterone (p less than 0.01) and PRA (p less than 0.01) were significantly increased. There was a significant difference between class II patients and class III patients in plasma ANF (p less than 0.01) and noradrenaline (p less than 0.02) concentrations, but not in PRA and aldosterone levels. A significant correlation was observed between plasma ANF concentration and left ventricular end-diastolic pressure (r = 0.68, p less than 0.001), pulmonary arterial pressure (r = 0.59, p less than 0.01), pulmonary capillary pressure (r = 0.51, p less than 0.02), cardiac index (r = 0.46, p less than 0.05) and left ventricular end-diastolic volume (r = 0.50, p less than 0.05). However, ANF concentration was not correlated with mean right atrial pressure. Plasma adrenaline concentration correlated with systemic arterial resistance (r = 0.80, p less than 0.001), pulmonary arterial pressure (r = 0.57, p less than 0.02), mean pulmonary capillary pressure (r = 0.62, p less than 0.001), cardiac index (r = 0.53, p less than 0.05) and left ventricular end-diastolic pressure (r = 0.58, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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Fator Natriurético Atrial/sangue , Catecolaminas/sangue , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Sistema Renina-Angiotensina , Adulto , Idoso , Aldosterona/sangue , Pressão Sanguínea , Débito Cardíaco , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Renina/sangueRESUMO
Psychostimulants such as methylphenidate have been used for depression in cancer patients. We report the successful use of methylphenidate to treat depression in 10 consecutive patients with advanced cancer. A rapid onset of effect was noted. Appetite, concentration, fatigue, and sedation also improved in some persons. No severe side effects were noted.
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Estimulantes do Sistema Nervoso Central/uso terapêutico , Depressão/tratamento farmacológico , Depressão/etiologia , Metilfenidato/uso terapêutico , Neoplasias/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Cuidados Paliativos na Terminalidade da Vida/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Islam holds life as sacred and belonging to God and that all creatures will die one day. Suicide is forbidden. Muslims believe death is only a transition between two different lives. The terminally ill Muslim desires to perform five ritual requirements. Do not resuscitate (DNR) orders are acceptable. A deceased Muslim must always be buried after being ritually washed and wrapped. There are different Muslim schools of thought, but they are united regarding their views on death and dying.
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Atitude Frente a Morte/etnologia , Atitude Frente a Saúde/etnologia , Diversidade Cultural , Islamismo/psicologia , Assistência Terminal/psicologia , Ética Médica , Rituais Fúnebres , Pesar , Humanos , Defesa do Paciente/legislação & jurisprudência , Ordens quanto à Conduta (Ética Médica) , Assistência Terminal/métodos , Estados UnidosRESUMO
Cough is a common symptom in advanced cancer. Hydrocodone is the antitussive of choice in our palliative medicine inpatient unit. We reviewed the pharmacy records for the use of hydrocodone for all cancer admissions to our unit from May 1996 to December 1998. Median treatment duration with hydrocodone was three days (range 1-18). Median maximum daily dose was 15 mg (range 5-100), and median total dose during the hospital stay was 32 mg (range 5-455). Lung cancer as a primary cancer site was strongly related to the use of hydrocodone. The highest median duration of treatment (five days) was for esophageal cancer and the highest median maximum daily dose (35 mg) and total dose (75 mg) were for treating kidney cancer. This retrospective review provides information regarding the use of hydrocodone on the palliative medicine unit of the Cleveland Clinic Foundation. Controlled trials are needed to evaluate the efficacy and safety of hydrocodone for cough in advanced cancer.
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Antitussígenos/administração & dosagem , Tosse/tratamento farmacológico , Hidrocodona/administração & dosagem , Neoplasias/complicações , Idoso , Tosse/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
We conducted a prospective assessment of 50 consecutive admissions to an acute palliative medicine unit, using the bedside confusion scale (BSCS). Information including age, gender, diagnosis, and the presence or absence of brain metastasis was collected. Possible predisposing factors for delirium were recorded. Forty-one of 50 consecutive admissions were screened. There were 18 men and 23 women with a median age of 65 years (average: 60-75). The most common diagnoses among all were lung and breast cancer. Thirteen patients were delirious (BSCS score of > or = 2), 10 borderline (BSCS score = 1), and 21 normal (BSCS score = 0). Brain metastases and drugs appeared to be the most common predisposing factors of delirium. Forty percent of those that were delirious received haloperidol as symptomatic treatment. The BSCS is simple, portable, valid, quick, and easy to use by any medical team member. Delirium is common in hospitalized patients with advanced cancer.
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Confusão/classificação , Confusão/diagnóstico , Delírio/classificação , Delírio/diagnóstico , Neoplasias/complicações , Exame Neurológico/métodos , Quartos de Pacientes , Índice de Gravidade de Doença , Idoso , Estudos de Casos e Controles , Causalidade , Confusão/etiologia , Delírio/etiologia , Feminino , Avaliação Geriátrica , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Estudos Prospectivos , Fatores de TempoRESUMO
For any palliative medicine inpatient unit to be economically viable, certain management metrics need to be followed. Palliative medicine can provide both a compassionate and economical service within the current acute inpatient hospital environment. In this article, we will review the administrative and financial factors we have identified that influence the business of acute palliative medicine.
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Administração Financeira de Hospitais/organização & administração , Cuidados Paliativos na Terminalidade da Vida/organização & administração , Unidades Hospitalares/organização & administração , Cuidados Paliativos/organização & administração , Comércio , Grupos Diagnósticos Relacionados/economia , Custos Diretos de Serviços/estatística & dados numéricos , Custos Hospitalares/estatística & dados numéricos , Hospitais de Ensino , Humanos , Tempo de Internação/economia , Ohio , Planejamento de Assistência ao Paciente/organização & administração , Alta do Paciente , Admissão e Escalonamento de Pessoal/economiaRESUMO
Psychostimulants such as methylphenidate are used for fatigue in cancer patients. We report a prospective, open-label, pilot study of the successful use of methylphenidate to treat fatigue in nine of 11 consecutive patients with advanced cancer. Seven had received radiation or chemotherapy, a median of three weeks (range from one to 30 weeks) prior to methylphenidate. A rapid onset of benefit was noted, even in the presence of mild anemia. Sedation and pain also improved in some. Only one patient had side effects severe enough to stop the medication.
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Estimulantes do Sistema Nervoso Central/uso terapêutico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Metilfenidato/uso terapêutico , Neoplasias/complicações , Assistência Terminal/métodos , Idoso , Estimulantes do Sistema Nervoso Central/farmacologia , Evolução Fatal , Fadiga/diagnóstico , Feminino , Humanos , Masculino , Metilfenidato/farmacologia , Pessoa de Meia-Idade , Neoplasias/terapia , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
This article discusses the use of a medication kit at home for terminal symptoms. This innovation has been in place for more than two years at the Hospice of the Cleveland Clinic. There is no previously published information on this innovation in the literature.
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Tratamento Farmacológico/métodos , Emergências , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Assistência Terminal/métodos , Analgésicos Opioides/uso terapêutico , Ansiolíticos/uso terapêutico , Antieméticos/uso terapêutico , Atropina/uso terapêutico , Clorpromazina/uso terapêutico , Diazepam/uso terapêutico , Humanos , Morfina/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Ohio , Cuidados PaliativosRESUMO
UNLABELLED: This study evaluated the use of methylphenidate for depression in advanced cancer DESIGN: Phase II open-label prospective study. ELIGIBILITY CRITERIA: No previous use of methylphenidate or current use of other antidepressants. EVALUATION: Depression and response to treatment were determined by asking the patient: "are you depressed?" Patients were assessed at baseline and at days 3, 5, and 7. TREATMENT: Starting dose was 5 mg at 8:00 a.m. and 12:00 noon. The dose was titrated for lack of response on any of the assessment days. RESPONSE CRITERIA: A negative response to the question: "are you depressed?" RESULTS: Some 41 patients were enrolled and 30 (15 men, 15 women) completed the study. Median age was 68 years (range: 30-90). Methylphenidate was stopped for six patients because of side effects and five were not evaluable; 21 responded to 10 mg/day on day 3; the other nine responded to 20 mg/day on day 5, 29 maintained their positive response through day 7. Anorexia, fatigue, concentration, and sedation also improved in some. All who completed the study had tolerable side effects, none of which caused treatment to stop. CONCLUSIONS: Methylphenidate is effective for depression in advanced cancer A starting dose of 10 mg in divided doses is effective in most patients. Dose escalation may be needed. Improvement occurs within three days. Close monitoring of side effects is recommended.