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1.
N Engl J Med ; 384(14): 1323-1334, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33826820

RESUMO

BACKGROUND: Cold agglutinin disease is a rare autoimmune hemolytic anemia characterized by hemolysis that is caused by activation of the classic complement pathway. Sutimlimab, a humanized monoclonal antibody, selectively targets the C1s protein, a C1 complex serine protease responsible for activating this pathway. METHODS: We conducted a 26-week multicenter, open-label, single-group study to assess the efficacy and safety of intravenous sutimlimab in patients with cold agglutinin disease and a recent history of transfusion. The composite primary end point was a normalization of the hemoglobin level to 12 g or more per deciliter or an increase in the hemoglobin level of 2 g or more per deciliter from baseline, without red-cell transfusion or medications prohibited by the protocol. RESULTS: A total of 24 patients were enrolled and received at least one dose of sutimlimab; 13 patients (54%) met the criteria for the composite primary end point. The least-squares mean increase in hemoglobin level was 2.6 g per deciliter at the time of treatment assessment (weeks 23, 25, and 26). A mean hemoglobin level of more than 11 g per deciliter was maintained in patients from week 3 through the end of the study period. The mean bilirubin levels normalized by week 3. A total of 17 patients (71%) did not receive a transfusion from week 5 through week 26. Clinically meaningful reductions in fatigue were observed by week 1 and were maintained throughout the study. Activity in the classic complement pathway was rapidly inhibited, as assessed by a functional assay. Increased hemoglobin levels, reduced bilirubin levels, and reduced fatigue coincided with inhibition of the classic complement pathway. At least one adverse event occurred during the treatment period in 22 patients (92%). Seven patients (29%) had at least one serious adverse event, none of which were determined by the investigators to be related to sutimlimab. No meningococcal infections occurred. CONCLUSIONS: In patients with cold agglutinin disease who received sutimlimab, selective upstream inhibition of activity in the classic complement pathway rapidly halted hemolysis, increased hemoglobin levels, and reduced fatigue. (Funded by Sanofi; CARDINAL ClinicalTrials.gov number, NCT03347396.).


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Complemento C1s/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/terapia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Transfusão de Sangue , Fadiga/tratamento farmacológico , Fadiga/etiologia , Feminino , Hemoglobinas/análise , Hemólise/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
2.
Biofactors ; 47(2): 232-241, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33847020

RESUMO

COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.


Assuntos
/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Fadiga/tratamento farmacológico , Luteolina/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Encéfalo/virologia , /fisiopatologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/virologia , Citocinas/genética , Fadiga/complicações , Fadiga/fisiopatologia , Fadiga/virologia , Humanos , Mastócitos/efeitos dos fármacos , Mastócitos/virologia , /patogenicidade
3.
Adv Ther ; 38(3): 1536-1551, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33528792

RESUMO

INTRODUCTION: The efficacy of prolonged-release fampridine (PR-FAM) may extend in multiple sclerosis (MS) beyond walking ability. The objective of this study was to evaluate the effect of PR-FAM treatment on cognition, fatigue, depression, and quality of life (QoL) in adult patients with MS in a real-world setting. METHODS: FAMILY was a multi-center, prospective, observational, real-world cohort study of MS patients receiving PR-FAM in the outpatient setting. Patients were treated as per PR-FAM's local prescribing information for 6 months. Standardized protocols and questionnaires were used to evaluate changes in cognition (PASAT; Paced Auditory Serial Addition Test), fatigue (MFIS; Modified Fatigue Impact Scale), depression (BDI-II; Beck Depression Inventory-II) and QoL (MusiQoL; MS International Quality-of-Life questionnaire, MSIS-29; Multiple Sclerosis Impact Scale: PHYS and PSYCH subscales) at 3 and 6 months compared to baseline. RESULTS: In total, 102 eligible patients from 8 sites in Greece were analysed, of whom 92 completed the study and 10 discontinued. At 6 months, PR-FAM treatment resulted in improvements from baseline in PASAT-3'' (p = 0.044), MFIS (p < 0.001), BDI-II (p < 0.001), MusiQoL (p < 0.001) and MSIS-29-PHYS (p = 0.012) and MSIS-PSYCH (p < 0.001). A positive effect was evident already at 3 months in PASAT-3'' (ns), MFIS (p = 0.020), BDI-II (p = 0.034), MusiQoL (p = 0.001), MSIS-29-PHYS (ns) and MSIS-29-PSYCH (p < 0.001). CONCLUSIONS: This observational study provides new data to the current literature in support of PR-FAM's positive effects in cognition, fatigue, depression, and QoL in a large, heterogeneous group of Greek MS patients in the real-world setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03164018.


Assuntos
Esclerose Múltipla , Qualidade de Vida , Adulto , Cognição , Estudos de Coortes , Depressão/tratamento farmacológico , Fadiga/tratamento farmacológico , Grécia , Humanos , Esclerose Múltipla/tratamento farmacológico , Estudos Prospectivos
4.
JAMA Netw Open ; 4(2): e210369, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33576820

RESUMO

Importance: There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. Objective: To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. Design, Setting, and Participants: This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Intervention: Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. Outcomes: The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. Results: A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. Conclusions and Relevance: In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342728.


Assuntos
Ácido Ascórbico/uso terapêutico , Suplementos Nutricionais , Zinco/uso terapêutico , Adulto , Assistência Ambulatorial , Antioxidantes/uso terapêutico , Tosse/tratamento farmacológico , Tosse/etiologia , Dispneia/tratamento farmacológico , Dispneia/etiologia , Fadiga/tratamento farmacológico , Fadiga/etiologia , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Gluconatos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Padrão de Cuidado , Oligoelementos/uso terapêutico , Resultado do Tratamento
5.
Am J Clin Oncol ; 44(4): 137-142, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33512910

RESUMO

BACKGROUND: Fatigue is one of the most common adverse events of systemic therapy in patients with metastatic renal cell carcinoma (RCC). The aim of multicenter randomized phase 2 study was to determine the efficacy and safety of testosterone in patients with fatigue developed during targeted therapy. PATIENTS AND METHODS: Male patients with metastatic clear-cell RCC, normal prostate-specific antigen level, low testosterone level, and no evidence of hypothyroidism receiving first-line sunitinib or pazopanib with fatigue were randomly assigned (1:1) to either testosterone undecanoate (1000 mg) and targeted therapy or targeted therapy alone. The primary endpoint was the mean change of fatigue from baseline to 28 days according to the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary endpoints were safety, Functional Assessment of Cancer Therapy-Kidney Symptom Index 19, testosterone serum concentrations, red blood cell count, and hemoglobin level. RESULTS: Sixty patients were assigned to receive testosterone and targeted therapy (N=30) or targeted therapy alone (N=30). As of the data cutoff on December 30, 2019, median follow-up was 18.2 months. The study achieved its primary endpoint based on the significant differences at day 28 favoring testosterone over targeted therapy alone regarding the decreased level of fatigue (difference between groups, 22.5 points; 95% confidence interval, 18.4-26.6; P=0.012). Significant changes in scores demonstrating the enhanced quality of life with testosterone compared with targeted therapy were also observed for Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 disease-related symptoms (P=0.01). There were nonsignificant differences in red blood cell count and hemoglobin level between the 2 groups (all P>0.05). CONCLUSION: Male patients with metastatic RCC and hypogonadism receiving testosterone had less fatigue and better symptom control during targeted therapy.


Assuntos
Carcinoma de Células Renais/secundário , Fadiga/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Testosterona/análogos & derivados , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/tratamento farmacológico , Fadiga/etiologia , Fadiga/psicologia , Seguimentos , Humanos , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Qualidade de Vida , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico , Testosterona/efeitos adversos , Testosterona/uso terapêutico
6.
J Neurovirol ; 27(1): 12-25, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33367960

RESUMO

With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2," "COVID-19," and "meningoencephalitis." All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.


Assuntos
/fisiopatologia , Tosse/fisiopatologia , Fadiga/fisiopatologia , Febre/fisiopatologia , Meningoencefalite/fisiopatologia , /patogenicidade , Adulto , Idoso , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , /tratamento farmacológico , Confusão/diagnóstico por imagem , Confusão/tratamento farmacológico , Confusão/fisiopatologia , Confusão/virologia , Tosse/diagnóstico por imagem , Tosse/tratamento farmacológico , Tosse/virologia , Dispneia/diagnóstico por imagem , Dispneia/tratamento farmacológico , Dispneia/fisiopatologia , Dispneia/virologia , Eletroencefalografia , Fadiga/diagnóstico por imagem , Fadiga/tratamento farmacológico , Fadiga/virologia , Feminino , Febre/diagnóstico por imagem , Febre/tratamento farmacológico , Febre/virologia , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Meningoencefalite/diagnóstico por imagem , Meningoencefalite/tratamento farmacológico , Meningoencefalite/virologia , Pessoa de Meia-Idade , Neuroimagem , /efeitos dos fármacos
8.
J Stroke Cerebrovasc Dis ; 29(11): 105213, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066879

RESUMO

BACKGROUND: In stroke survivors, post-stroke fatigue predicts dependency in daily living and failure to return to work. Modafinil shows promise as a pharmacotherapy to reduce post-stroke fatigue and related sequelae, e.g., poorer functional and clinical outcomes. AIMS: This study explored the cost-effectiveness of modafinil in treating post-stroke fatigue in the Australian context, by determining its incremental cost-effectiveness ratio (ICER) and by simulating the potential cost-savings on a national scale, through a re-analysis of MIDAS trial data. METHODS: A post hoc cost-effectiveness analysis was undertaken. Part A: patient-level cost and health effect data (Multidimensional Fatigue Inventory (MFI) scores) were derived from the MIDAS trial and analysis undertaken from a health-system perspective. Part B: a secondary analysis simulated the societal impact of modafinil therapy in terms of national productivity costs. RESULTS: Part A: Mean cost of modafinil treatment was AUD$3.60/day/patient for a minimally clinically important change (10 points) in total MFI fatigue score, i.e., AUD$0.36/day/unit change in fatigue score per patient. For the base case scenario, the ICER of using modafinil (versus placebo) was AUD$131.73 ($90.17 - 248.15, for minimum and maximum costs, respectively). Part B: The potential productivity cost-savings to society were calculated as nearly AUD$467 million over 1 year, and up to $383,471,991,248 over 10 years, from the widespread use of modafinil treatment in the Australian population of working-age stroke-survivors, representing a significant societal benefit. CONCLUSIONS: Modafinil is a highly cost-effective treatment for post-stroke fatigue, offering significant productivity gains and potential cost-savings to society from the widespread use of modafinil treatment in the Australian population of working-age stroke-survivors.


Assuntos
Estimulantes do Sistema Nervoso Central/economia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Custos de Medicamentos , Fadiga/tratamento farmacológico , Fadiga/economia , Modafinila/economia , Modafinila/uso terapêutico , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/terapia , Idoso , Austrália , Estimulantes do Sistema Nervoso Central/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Redução de Custos , Análise Custo-Benefício , Fadiga/diagnóstico , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/efeitos adversos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
9.
Nat Commun ; 11(1): 3737, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32719355

RESUMO

Glucocorticoids (GC) are a controversial yet commonly used intervention in the clinical management of acute inflammatory conditions, including sepsis or traumatic injury. In the context of major trauma such as surgery, concerns have been raised regarding adverse effects from GC, thereby necessitating a better understanding of how GCs modulate the immune response. Here we report the results of a randomized controlled trial (NCT02542592) in which we employ a high-dimensional mass cytometry approach to characterize innate and adaptive cell signaling dynamics after a major surgery (primary outcome) in patients treated with placebo or methylprednisolone (MP). A robust, unsupervised bootstrap clustering of immune cell subsets coupled with random forest analysis shows profound (AUC = 0.92, p-value = 3.16E-8) MP-induced alterations of immune cell signaling trajectories, particularly in the adaptive compartments. By contrast, key innate signaling responses previously associated with pain and functional recovery after surgery, including STAT3 and CREB phosphorylation, are not affected by MP. These results imply cell-specific and pathway-specific effects of GCs, and also prompt future studies to examine GCs' effects on clinical outcomes likely dependent on functional adaptive immune responses.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Artroplastia de Quadril/efeitos adversos , Glucocorticoides/farmacologia , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/imunologia , Doença Aguda , Idoso , Estudos de Casos e Controles , Método Duplo-Cego , Fadiga/tratamento farmacológico , Feminino , Humanos , Masculino , Metilprednisolona/farmacologia , Metilprednisolona/uso terapêutico , Inibidor de NF-kappaB alfa/metabolismo , Dor/tratamento farmacológico , Fenótipo , Fosforilação , Fator de Transcrição STAT3/metabolismo , Resultado do Tratamento
10.
J Cancer Res Clin Oncol ; 146(10): 2479-2487, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32617701

RESUMO

PURPOSE: Fatigue is a distressing symptom in head & neck cancer patients before during and at the end of curative therapy. Pharmacologic and not pharmacologic treatments have been proposed with scarce or no evidence of efficacy. The aim of the study is to evaluate the efficacy of American ginseng in respect to placebo in reducing fatigue in patients treated for head and neck cancer with curative intent. METHODS: Thirty-two patients who had completed oncological treatment for a primary Head & neck tumor for at least 1 year and had a global fatigue score > 4 by means of Brief Fatigue Inventory (BFI) were randomized to receive 1000 mg of American ginseng or placebo per day for 8 weeks with the aim to assess their efficacy. Changes in fatigue scores in the 2 subgroups of patients before and after the treatment with American ginseng or placebo, were assessed by the BFI at baseline and at the end of week 8. RESULTS: The mean of the mean values of the BFI measured at 8 weeks (end of treatment) was 4.6 in the Ginseng arm and 3.4 in the Placebo arm (p = ns). Mean comparison showed a tendency to statistical significance only for the single item on interference with general activity (p = 0.06), with better performance for placebo. The mean of the differences between baseline values and 8 weeks values was not significantly different between treatment arms considering the entire questionnaire. CONCLUSION: The present data shows that American ginseng has insufficient evidence to be recommended for Cancer Related Fatigue (CRF) in post treatment HNC survivors.


Assuntos
Fadiga/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/terapia , Panax , Adulto , Idoso , Fadiga/diagnóstico , Fadiga/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fitoterapia/métodos
11.
J Food Sci ; 85(6): 1897-1906, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32449949

RESUMO

The anshenyizhi compound (AC), a mixture from Chinese medicine herbs, has numerous biological effects. In the present study, the acute exercise-treated mice model was established to explore the antifatigue properties of AC and its underlying mechanisms. AC increased exercise endurance in the weight-loaded forced swimming test and rota-rod test. The antifatigue properties of AC were closely correlated with enhancing the body's exercise endurance by increasing the levels of cyanmethemoglobin, testosterone/corticosterone, and creatine kinase, while decreasing the levels of lactic acid, lactate dehydrogenase, and blood urea nitrogen in serum. Moreover, our results confirmed the antioxidant ability of AC by improving the activities of superoxide dismutase while reducing reactive oxygen species and malondialdehyde levels in serum. The AC also improved the storage of glycogen by increasing the levels of succinate dehydrogenase, and malate dehydrogenase in liver and muscle. Additionally, AC displayed the antifatigue and antiapoptosis effects via regulating Nrf2-mediated oxidative stress, AMPK-related glucose metabolism, and p53 pathways. Our experimental results first provided a support that AC had effects on antifatigue through regulating AMPK/PGC-1α-related energy metabolism and Nrf2/ARE-mediated oxidative stress. Consequently, AC could be developed into a new functional food supplement for the prevention and treatment of diseases related to fatigue in the future.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Fadiga/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transativadores/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Antioxidantes/metabolismo , Metabolismo Energético , Fadiga/genética , Fadiga/metabolismo , Glicogênio/metabolismo , Humanos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Natação , Transativadores/genética
12.
Eur J Cancer ; 130: 51-62, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32172198

RESUMO

BACKGROUND: Cancer-related fatigue (CRF) is a common symptom and has a negative impact on prognosis in cancer patients. CRF could be improved by Korean red ginseng (KRG). PATIENTS AND METHODS: For this randomised and double-blinded trial, colorectal cancer patients who received mFOLFOX-6 were randomly assigned to either KRG 2000 mg/day (n = 219) or placebo (n = 219) for 16 weeks. CRF was evaluated using the mean area under the curve (AUC) change from baseline of brief fatigue inventory (BFI) as the primary endpoint. Fatigue-related quality of life, stress, and adverse events were evaluated as secondary endpoints. RESULTS: In the full analysis group, KRG up to 16 weeks improved CRF by the mean AUC change from baseline of BFI compared to placebo, particularly in "Mood" and "Walking ability" (P = 0.038, P = 0.023, respectively). In the per-protocol group, KRG led to improved CRF in the global BFI score compared with the placebo (P = 0.019). Specifically, there were improvements in "Fatigue right now," "Mood," "Relations with others," "Walking ability," and "Enjoyment of life" at 16 weeks (P = 0.045, P = 0.006, P = 0.028, P = 0.003, P = 0.036, respectively). In subgroups of female patients, ≥60 years old, with high compliance (≥80%) or more baseline fatigue, the beneficial effects of KRG were more enhanced than that of placebo. Although neutropenia was more frequent in KRG than placebo, the incidence of all adverse events was similar. CONCLUSIONS: KRG could be safely combined with mFOLFOX-6 chemotherapy in colorectal cancer patients, and reduced CRF compared with placebo.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Fadiga/tratamento farmacológico , Panax/química , Qualidade de Vida/psicologia , Neoplasias Colorretais/complicações , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
13.
Leukemia ; 34(9): 2430-2440, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32094461

RESUMO

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1-2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.


Assuntos
Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Hidrazinas/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Triazóis/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Apetite/efeitos dos fármacos , Diarreia/induzido quimicamente , Fadiga/induzido quimicamente , Fadiga/tratamento farmacológico , Feminino , Humanos , Hidrazinas/uso terapêutico , Hiponatremia/induzido quimicamente , Hiponatremia/terapia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Triazóis/uso terapêutico
14.
J Clin Oncol ; 38(9): 905-914, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32023162

RESUMO

Good symptom management in oncology is associated with improved patient and family quality of life, greater treatment compliance, and may even offer survival advantages. With population growth and aging, the proportion of patients with multiple symptoms-both related and unrelated to their cancer-is anticipated to increase, supporting calls for a more routine and integrated approach to symptom management. This article presents a summary of the literature for the use of symptom assessment tools and reviews the management of four common and distressing symptoms commonly experienced by people with advanced cancer: pain, breathlessness, nausea and vomiting, and fatigue. We also discuss the role of palliative care in supporting a holistic approach to symptom management throughout the cancer trajectory.


Assuntos
Dispneia/tratamento farmacológico , Fadiga/tratamento farmacológico , Náusea/tratamento farmacológico , Neoplasias/complicações , Dor/tratamento farmacológico , Cuidados Paliativos/normas , Vômito/tratamento farmacológico , Gerenciamento Clínico , Dispneia/etiologia , Fadiga/etiologia , Humanos , Náusea/etiologia , Dor/etiologia , Vômito/etiologia
15.
Medicine (Baltimore) ; 99(5): e18968, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000424

RESUMO

BACKGROUND: Lung cancer is one of the most common cancers worldwide, and approximately half of the patients with lung cancer receiving chemotherapy suffer from cancer-related fatigue (CRF). Herbal medicines (HMs) have been used in Oriental countries for centuries as tonics. Various beneficial effects of HM on fatigue and cancer have been reported. However, the effectiveness and safety of HM for CRF in lung cancer patients have not been synthesized. The purpose of this systematic review is to evaluate the effectiveness and safety of HM for CRF in patients with lung cancer, regardless of their cancer type or stage. METHODS AND ANALYSIS: A comprehensive search will be conducted in 12 electronic medical databases including 5 English-language databases (Medline via PubMed, EMBASE via Elsevier, the Cochrane Central Register of Controlled Trials [CENTRAL], the Allied and Complementary Medicine Database [AMED] via EBSCO, and the Cumulative Index to Nursing and Allied Health Literature [CINAHL] via EBSCO), 4 Korean-language databases (Oriental Medicine Advanced Searching Integrated System [OASIS], Koreanstudies Information Service System [KISS], Research Information Service System [RISS], and Korea Citation Index [KCI]), 2 Chinese-language databases (China National Knowledge Infrastructure [CNKI] and Wanfang Data), and 1 Japanese-language database (CiNii). Only randomized controlled trials (RCTs) and quasi-RCTs on HM for CRF will be allowed. The severity of fatigue assessed using a validated tool will be considered as theprimary outcome. The secondary outcomes will include the patients' quality of life, activities of daily life, incidence of adverse events, and total effective rate. Two independent researchers will perform the study selection, data extraction, and quality assessment. RevMan version 5.3 will be used for data synthesis. The methodological quality of the included RCTs will be assessed using the Cochrane Collaboration's risk of bias tool. In the meta-analysis, for dichotomous data and continuous data, risk ratio and mean difference, respectively, will be estimated with their 95% confidence intervals. According to the heterogeneity, either a fixed-effects or a random-effects model will be used. ETHICS AND DISSEMINATION: Ethical approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through a peer-reviewed publication or conference presentation. PROSPERO REGISTRATION NUMBER: CRD42019141660.


Assuntos
Sobreviventes de Câncer , Medicamentos de Ervas Chinesas/uso terapêutico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Medicina Herbária/métodos , Neoplasias Pulmonares/complicações , Medicina Tradicional do Leste Asiático/métodos , Revisões Sistemáticas como Assunto , Humanos , Projetos de Pesquisa
16.
Curr Gastroenterol Rep ; 22(2): 8, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002666

RESUMO

PURPOSE OF REVIEW: The bidirectional relationship between sleep disorders and inflammatory bowel disease (IBD) has gained considerable attention in recent years. It has been suggested that poor sleep and fatigue are extra-intestinal manifestations of IBD. This review reports recent studies exploring subjective and objective assessments of sleep in the adult IBD population. RECENT FINDINGS: In ulcerative colitis patients, poor sleep has been independently linked to depression and poorer IBD-related quality of life. Using home polysomnography, IBD patients were shown to have less rapid eye movement sleep and Crohn's patient had increased lighter sleep. A study utilizing surveys assessing circadian rhythms described circadian misalignment in IBD patients and reported that circadian misalignment in Crohn's disease was associated with a more aggressive disease phenotype. The use of biologics may improve sleep disturbances in patients with IBD. Translational and clinical studies have reported that disturbances in sleep quality are linked to intestinal inflammation and a heighted systemic immune response. IBD patients appear to have disturbed sleep. Poor sleep is also suggested as a marker for subclinical disease activity. Recent studies have suggested circadian misalignment in IBD patients, and future studies are needed to assess these clinical implications.


Assuntos
Fadiga/etiologia , Doenças Inflamatórias Intestinais/complicações , Transtornos do Sono-Vigília/etiologia , Produtos Biológicos/uso terapêutico , Ritmo Circadiano/fisiologia , Disbiose/fisiopatologia , Fadiga/tratamento farmacológico , Fadiga/fisiopatologia , Humanos , Inflamação/fisiopatologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/fisiopatologia , Polissonografia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/fisiopatologia
17.
Neth J Med ; 78(1): 34-36, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32043476

RESUMO

Iron deficiency, without anaemia, is common in the general population and induces various symptoms. Its management consists of oral and intravenous supplementation for cases of inefficacy of or intolerance to oral iron. We assessed the efficacy of intravenous iron therapy in non-anaemic iron-deficient patients with fatigue. We prospectively evaluated the level of fatigue, using the Fatigue Severity Scale (FSS), in patients suffering from iron deficiency without anaemia, treated by intravenous iron at the moment of the perfusion (W0), after 4 weeks (W4), and 12 weeks (W12). Of 25 patients, at W0, the mean FFS was 49.3+/-13.7. There was a significant improvement in FSS at W4 (44+/-15; p = 0.01) and a sustained response at W12 with an FFS of 35.8+/-17.1 (p < 0,0001). There was no correlation between FSS and serum ferritin level at W12 (p=0.54) or between serum ferritin at W12 and difference between FSS at W0 and W12 (p=0.58). There were six mild adverse events (24%): asthenia (8%), nausea (8%), headache (4%), local pain (4%); and no serious adverse events. Our results suggest the rapid efficacy of intravenous iron in improving fatigue in iron deficiency without anaemia with a good profile of tolerance.


Assuntos
Fadiga/tratamento farmacológico , Ferro/deficiência , Ferro/farmacologia , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Fadiga/complicações , Feminino , Humanos , Ferro/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
18.
BMC Cancer ; 20(1): 158, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106832

RESUMO

BACKGROUND AND OBJECTIVES: Cancer-related fatigue (CRF) is one of the most prevalent complications experienced by cancer patients during and after the process of treatment. Despite conducting a lot of studies, there is no approved therapy to help manage CRF. This study aims to investigate the efficacy of bupropion on CRF. MATERIALS AND METHODS: In this double-blind randomized placebo-controlled clinical trial, a total of 30 eligible cancer patients suffering from fatigue were randomly divided into two groups (15 patients in each group). Bupropion was administered 75 mg/day for the first three days and 150 mg/day (divided in two doses) till the end of the study at week 6. Fatigue as the primary outcome was measured by BFI (Brief Fatigue Inventory) and FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy) scales. Secondary outcomes included HADS (Hospital Anxiety and Depression Scale) and performance status (PS) measured by Karnofsky and ECOG (Eastern Cooperative Oncology Group) scales. Assessments were done at baseline, end of the second and sixth week. RESULTS: There was no significant difference between placebo and bupropion at baseline and the end of second week. Significant difference was seen between two groups at the end of week six (P = 0.006 based on BFI) in favor of bupropion. In-group assessment showed improvement in fatigue levels in both groups during study time (P = 0.000 based on BFI for both bupropion and placebo). Secondary outcomes (e.g., HADS and PS) were not different at baseline and the end of second week. However, at the end of week six, the difference was significant in favor of bupropion. CONCLUSION: A six-week trial of bupropion reduces the CRF and improves the PS of cancer patients. TRIAL REGISTRATION: Current Controlled Trials IRCT20090613002027N12, registration date: 2018-06-01.


Assuntos
Bupropiona/administração & dosagem , Fadiga/tratamento farmacológico , Neoplasias/complicações , Adulto , Idoso , Bupropiona/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Nutrients ; 12(1)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963141

RESUMO

Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Fadiga/tratamento farmacológico , Minerais/administração & dosagem , Vitaminas/administração & dosagem , Afeto/efeitos dos fármacos , Animais , Ácido Ascórbico/administração & dosagem , Deficiência de Ácido Ascórbico/metabolismo , Deficiência de Ácido Ascórbico/fisiopatologia , Deficiência de Ácido Ascórbico/prevenção & controle , Deficiência de Ácido Ascórbico/psicologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Fadiga/metabolismo , Fadiga/fisiopatologia , Fadiga/psicologia , Humanos , Ferro/administração & dosagem , Magnésio/administração & dosagem , Minerais/efeitos adversos , Estado Nutricional , Complexo Vitamínico B/administração & dosagem , Deficiência de Vitaminas do Complexo B/metabolismo , Deficiência de Vitaminas do Complexo B/fisiopatologia , Deficiência de Vitaminas do Complexo B/prevenção & controle , Deficiência de Vitaminas do Complexo B/psicologia , Vitaminas/metabolismo , Zinco/administração & dosagem
20.
J Urol ; 203(6): 1184-1190, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31928462

RESUMO

PURPOSE: We explored the Medicare database (1999 to 2014) to provide a comprehensive assessment of testosterone therapy patterns in the older U.S. male population. MATERIALS AND METHODS: We estimated annual age-standardized incidence (new users) and prevalence (existing users) of testosterone therapy according to demographic characteristics, comorbidities and potential indications. RESULTS: There were 392,698 incident testosterone therapy users during 88 million person-years. Testosterone therapy users were predominantly younger, white nonHispanic, and located in South and West U.S. Census regions. On average testosterone therapy use increased dramatically during 2007 to 2014 (average annual percent change 15.5%), despite a decrease in 2014. In 2014 the most common recorded potential indications for any testosterone therapy were hypogonadism (48%), fatigue (18%), erectile dysfunction (15%), depression (4%) and psychosexual dysfunction (1%). Laboratory tests to measure circulating testosterone concentrations for testosterone therapy were infrequent with 35% having had at least 1 testosterone test in the 120 days preceding testosterone therapy, 4% the recommended 2 pre-testosterone therapy tests, and 16% at least 1 pre-testosterone therapy test and at least 1 post-testosterone therapy test. CONCLUSIONS: Testosterone therapy remains common in the older U.S. male population, despite a recent decrease. Although testosterone therapy prescriptions are predominantly for hypogonadism, a substantial proportion appear to be for less specific conditions. Testosterone tests among men prescribed testosterone therapy appear to be infrequent.


Assuntos
Androgênios/uso terapêutico , Uso de Medicamentos/tendências , Terapia de Reposição Hormonal/tendências , Padrões de Prática Médica/tendências , Testosterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Depressão/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Fadiga/tratamento farmacológico , Humanos , Hipogonadismo/tratamento farmacológico , Estudos Longitudinais , Masculino , Medicare , Estudos Retrospectivos , Estados Unidos
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