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1.
Pediatr Rheumatol Online J ; 19(1): 127, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404425

RESUMO

BACKGROUND: High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing. METHODS: We retrospectively reviewed the records at a single tertiary-care children's hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis, and complications from treatment. RESULTS: Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (IQR 3-7.5). Myositis control was achieved in a median of 7.1 months (IQR 0.9-63.4). Cutaneous disease control was achieved in a median of 16.7 months (IQR 4.3-89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (IQR 0.5-1.74). The median duration of steroid treatment was 9.1 months, (IQR 4.7-17.4), while the median duration of any pharmacotherapy was 29.2 months (IQR 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%). CONCLUSION: Current accepted treatment paradigms for Juvenile Dermatomyositis include oral glucocorticoids beginning at 2 mg/kg/day and reduced over a prolonged time period. However, our results suggest that treatment using reduced doses and duration with early use of steroid-sparing agents is comparably effective in achieving favorable outcomes in Juvenile Dermatomyositis.


Assuntos
Calcinose , Dermatomiosite , Redução da Medicação/métodos , Duração da Terapia , Glucocorticoides , Administração Oral , Terapia Biológica/métodos , Calcinose/etiologia , Calcinose/prevenção & controle , Criança , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Indução de Remissão/métodos , Avaliação de Sintomas/métodos , Estados Unidos/epidemiologia
2.
Biomed Pharmacother ; 138: 111403, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33714782

RESUMO

Gu-Ben-Fang-Xiao decoction (GBFXD), derived from the traditional Chinese medicine Yu-Ping-Feng-San, is widely used in clinical settings and has obvious curative effects in respiratory diseases. GBFXD regulates cholesterol transport and lipid metabolism in chronic persistent asthma. There is evidence for its beneficial effects in the remission stage of asthma; however, its metabolic regulatory effects and underlying mechanisms during asthma remission are unclear. In the present study, we used liquid chromatography-mass spectrometry (LC-MS) to analyse the metabolic profile of mouse serum during asthma remission. The acquired LC-MS data were subjected to a multivariate analysis for identification of significantly altered metabolites. In total, 42 metabolites were significantly differentially expressed among the control, model, and GBFXD groups. In particular, levels of fatty acids, acylcarnitines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, triglycerides, and diacylglycerols were altered during asthma remission. GBFXD may maintain lipid homeostasis on the lung surface by modulating lipid metabolism and may thereby alleviate asthma. We further quantified hypogeic acid (FA 16:1) based on targeted metabolomics and found that GBFXD may regulate fatty acid metabolism by activating the AMP-activated protein kinase (AMPK) pathway. These results support the use of GBFXD in patients with asthma remission.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Asma/tratamento farmacológico , Asma/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Ativadores de Enzimas/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Ativadores de Enzimas/farmacologia , Feminino , Metabolismo dos Lipídeos/fisiologia , Metabolômica/métodos , Camundongos , Indução de Remissão/métodos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
3.
PLoS One ; 16(2): e0246871, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571293

RESUMO

BACKGROUND: Cannabis is often used by patients with ulcerative colitis, but controlled studies are few. We aimed to assess the effect of cannabis in improving clinical and inflammatory outcomes in ulcerative colitis patients. METHODS: In a double-blind, randomized, placebo-controlled trial, patients received either cigarettes containing 0.5 g of dried cannabis flowers with80mgTetrahydrocannabinol (THC)or placebo cigarettes for 8 weeks. Parameters of disease including Lichtiger disease activity index, C reactive protein (CRP), calprotectin, Mayo endoscopic score and quality of life (QOL) were assessed before, during and after treatment. RESULTS: The study included 32 patients. Mean age was 30 years, 14 (43%) females. Lichtiger index improved in the cannabis group from 10.9 (IQR 9-14) to5 (IQR 1-7), (p<0.000), and in the placebo group from 11 (IQR 9-13) to 8 (IQR 7-10)(p = 0.15, p between groups 0.001). QOL improved in the cannabis group from 77±4 to 98±20 (p = 0.000) but not in the placebo group (78±3 at week 0 and 78±17 at week 8;p = 0.459; p between groups 0.007). Mayo endoscopic score changed in the cannabis group from 2.13±1 to 1.25±2 (p = 0.015) and in the placebo group from 2.15±1to 1.69±1 (p = 0.367, p between groups 0.17). CONCLUSION: Short term treatment with THC rich cannabis induced clinical remission and improved quality of life in patients with mild to moderately active ulcerative colitis. However, these beneficial clinical effects were not associated with significant anti-inflammatory improvement in the Mayo endoscopic score or laboratory markers for inflammation.(clinicaltrials.gov NCT01040910).


Assuntos
Colite Ulcerativa/tratamento farmacológico , Maconha Medicinal/uso terapêutico , Qualidade de Vida , Indução de Remissão/métodos , Adulto , Colite Ulcerativa/diagnóstico por imagem , Método Duplo-Cego , Endoscopia , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Br J Haematol ; 193(2): 346-355, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33368155

RESUMO

Targeted therapy for chronic myeloid leukaemia (CML) has allowed for a near-normal patient life-expectancy; however, quality of life and aggravation of existing co-morbidities have posed new treatment challenges. In clinical practice, TKI dose reduction occurs frequently, often on multiple occasions, because of intolerance. We conducted a retrospective 'real-world practice' review of 246 patients receiving lower than standard dose (LD) TKI after the achievement of major molecular response (MR3), because of intolerable adverse events. In 274 of 298 cases of dose reduction (91·9%), MR3 was maintained at median follow-up of 27·3 months. One patient progressed to blast crisis while on LD TKI. Two patients developed two new ABL kinase domain mutations (T315I and V299L), of whom one had achieved deep molecular response on an alternative LD TKI at last follow-up. Seventy-six patients eventually discontinued LD TKI and the two-year treatment-free remission (TFR) rate in these patients was 74·1%. The majority of patients with CML in at least MR3 appear to be safely managed with LD TKI, although three of 246 patients had new events (progression and new mutation), indicating that this approach requires vigilance. TKI LD does not prevent the achievement of TFR in this patient population.


Assuntos
Redução da Medicação/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Indução de Remissão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Compostos de Anilina/uso terapêutico , Comorbidade , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Dasatinibe/uso terapêutico , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Mutação , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Qualidade de Vida , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Estudos Retrospectivos , Segurança , Resultado do Tratamento
6.
Nat Commun ; 11(1): 4458, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895383

RESUMO

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Hipotálamo/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteína Relacionada com Agouti/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicemia/análise , Comunicação Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/administração & dosagem , Sacarose Alimentar/efeitos adversos , Humanos , Hipotálamo/citologia , Hipotálamo/patologia , Injeções Intraventriculares , Leptina/genética , Masculino , Melanocortinas/metabolismo , Hormônios Estimuladores de Melanócitos/administração & dosagem , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , RNA-Seq , Receptor Tipo 4 de Melanocortina/genética , Receptores de Melanocortina/antagonistas & inibidores , Receptores de Melanocortina/metabolismo , Indução de Remissão/métodos , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Técnicas Estereotáxicas , Transcriptoma/efeitos dos fármacos
7.
Integr Cancer Ther ; 19: 1534735419895591, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32070148

RESUMO

Background: This is a retrospective study to examine the effect of chemotherapy with or without intravenous vitamin C (IVC) on women with advanced triple-negative breast cancer (TNBC). Methods: From 2008 to 2016, a total of 113 patients with pathologically confirmed TNBC at Clifford Hospital were evaluated, and 70 patients were matched and divided into IVC (treatment group) and non-IVC groups (control group). The match was according to age, menopausal status, and metastatic sites. In the control group, 35 patients received gemcitabine and carboplatin. In the treatment group, 35 patients received the same chemotherapy plus IVC. Results: Baseline characteristics were not significantly different between the 2 groups. According to the criteria of RECIST 1.1 (Response Evaluation Criteria in Solid Tumors), enhanced computed tomography scan was compared after 2 cycles of chemotherapy. In the treatment group, 2/35 cases had a complete remission (CR), 15/35 cases had partial remission (PR), and 13/35 cases had stable disease (SD). The response rate was 48.6%. In the control group, there were no CR cases, 14/35 cases had PR, 14/35 cases had SD, and the response rate was 40.0% (P > .05). The median progression-free survival time and median overall survival time was 7 months (95% confidence interval [CI] =1.5-28.5 months) and 27 months (95% CI = 4-40 months) in the treatment group compared with 4.5 months (95% CI = 1.5-8 months) and 18 months (95% CI = 3-26 months) in the control group (P < .05). All patients experienced diverse reactions in the gastrointestinal tract and myelosuppression. The incidence of adverse reactions in the treatment group was significantly lower than that of the control group (P < .05). Conclusion: IVC may have an effect on improving the prognosis of patients with advanced TNBC.


Assuntos
Ácido Ascórbico/administração & dosagem , Mama , Carboplatina , Desoxicitidina/análogos & derivados , Neoplasias de Mama Triplo Negativas , Fatores Etários , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Mama/diagnóstico por imagem , Mama/patologia , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão/métodos , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Vitaminas/administração & dosagem , Gencitabina
8.
Support Care Cancer ; 28(9): 4381-4393, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31916008

RESUMO

PURPOSE: Differences in body weight changes and serum liver tests (LTs) in acute myeloid leukemia (AML) patients receiving parenteral nutrition (PN) versus no PN during remission induction (RI) treatment were assessed. METHODS: Retrospectively, differences in body weight changes and serum LTs in AML patients (n = 213) who received PN versus no PN during RI treatment in one of three Dutch hospitals between 2004 and 2015 were assessed. Weekly body weight and serum LT registrations were collected from medical records. Patients' body weight changes were compared between the hospitals where PN is applied upon first indication of inadequate oral intake (PN hospitals) and the hospital where use of PN is limited to severe cases only (no-PN hospital) using repeated measures mixed model analysis. Differences in severity of serum LT elevations, according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, were assessed between patients who did and did not receive PN using chi-square or Fisher's exact tests, and multiple logistic regression analysis. RESULTS: Compared with patients of the PN hospitals, patients of the no-PN hospital experienced significantly more body weight loss during RI treatment (between-group difference 7.2%, 95% CI 4.0-10.3%). Furthermore, PN was associated with transient mild to moderate elevations of liver enzymes, but not with raised median total bilirubin levels nor with occurrence of CTCAE grade 3-4 LT elevations. CONCLUSION: Frequent compared with exceptional use of PN in AML patients during RI treatment better preserved body weight, without clinically relevant (CTCAE grade 3-4) elevations in serum LTs.


Assuntos
Peso Corporal/efeitos dos fármacos , Leucemia Mieloide Aguda/terapia , Fígado/metabolismo , Nutrição Parenteral/métodos , Indução de Remissão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Trials ; 21(1): 7, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898521

RESUMO

BACKGROUND: Acute promyelocytic leukemia (APL) is a highly curable disease when treated with all-trans retinoid acid (ATRA) and arsenic trioxide (ATO). The combination of ATO and ATRA has become the standard therapeutic protocol for induction therapy in non-high-risk APL. An oral arsenic realgar-indigo naturalis formula (RIF) has also showed high efficacy and it has a more convenient route of administration than the standard intravenous regimen. Unlike in previous trials, the arsenical agent was used simultaneously with ATRA during post-remission therapy in this trial. METHODS: This study was designed as a multicenter, randomized controlled trial. The trial has a non-inferiority design with superiority being explored if non-inferiority is identified. All patients receive ATRA-ATO during the induction therapy. After achieving hematologic complete remission (HCR), patients were randomly assigned (1:1) to receive treatment with ATRA-RIF (experimental group) or ATRA-ATO (control group) as the consolidation therapy. During the consolidation therapy, the two groups receive ATRA plus RIF or intravenous ATO 2 weeks on and 2 to ~ 4 weeks off until molecular complete remission (MCR), then ATRA and oral RIF 2 weeks on and 2 to ~ 4 weeks off giving a total of six courses. DISCUSSION: This trial aims to compare the efficacy of ATRA-ATO versus ATRA-RIF in non-high-risk patients with APL, to demonstrate that oral RIF application reduces the total hospitalization days and medical costs. The simple schedule was studied in this trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02899169. Registered on 14 September 2016.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Indução de Remissão/métodos , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Terapia Neoadjuvante , Resultado do Tratamento
10.
Clin Transl Gastroenterol ; 12(1): e00287, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33464732

RESUMO

INTRODUCTION: Thetanix (gastroresistant capsules containing lyophilized Bacteroides thetaiotaomicron) is a live biotherapeutic, under development for Crohn's disease, that antagonizes transcription factor nuclear factor kappa B, reducing proinflammatory cytokines, particularly tumor necrosis factor alpha. We aimed to assess safety and tolerability in adolescents with Crohn's disease in remission. METHODS: Subjects who were 16-18 years with Crohn's in remission (weighted pediatric Crohn's disease activity index <12.5) were recruited. Each active dose comprised ∼108.2±1.4 colony forming units of B. thetaiotaomicron (randomized 4:1 active:placebo). Part A was single dose. Part B involved 7.5 days twice daily dosing. Serial stools were analyzed for calprotectin, 16S rRNA sequencing, and B. thetaiotaomicron real-time polymerase chain reaction. Bloods were taken serially. Subjects reported adverse events and recorded temperature twice daily. RESULTS: Fifteen subjects were treated-8 in part A (75% men, median 17.1 years) and 10 in part B, including 3 from part A (80% men, median 17.1 years); all 18 completed. Seventy percent took concurrent immunosuppression. Reported compliance was >99% in part B. Two subjects reported adverse events deemed related-one in part A with eructation, flatulence, and reflux; one in part B with dizziness, abdominal pain, and headache. No serious adverse events were reported. There was no significant change in median calprotectin across part B (87.8 [4.4-447] to 50.5 [5.3-572], P = 0.44 by the Fisher exact test in the active group). No significant differences were found in microbiota profiles, but diversity seemed to increase in treated subjects. DISCUSSION: Thetanix, after single and multiple doses, was well tolerated. Although the numbers in this study were small, the safety profile seems good. Future studies should explore efficacy.


Assuntos
Terapia Biológica/efeitos adversos , Doença de Crohn/terapia , Adolescente , Bacteroides thetaiotaomicron , Terapia Biológica/métodos , Doença de Crohn/imunologia , DNA Bacteriano/isolamento & purificação , Método Duplo-Cego , Feminino , Seguimentos , Liofilização , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Humanos , Masculino , Placebos/administração & dosagem , Placebos/efeitos adversos , RNA Ribossômico 16S/genética , Indução de Remissão/métodos , Resultado do Tratamento
11.
Cancer ; 126(2): 344-353, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31580501

RESUMO

BACKGROUND: Omacetaxine mepesuccinate (OME) has antileukemic effects against acute myeloid leukemia (AML) carrying an internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3-ITD). A phase 2 clinical trial was conducted to evaluate a combination treatment of sorafenib and omacetaxine mepesuccinate (SOME). METHODS: Relapsed or refractory (R/R) or newly diagnosed patients were treated with sorafenib (200-400 mg twice daily) and OME (2 mg daily) for 7 (first course) or 5 days (second course onward) every 21 days until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). The primary endpoint was composite complete remission, which was defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi). Secondary endpoints were leukemia-free survival (LFS) and overall survival (OS). RESULTS: Thirty-nine R/R patients and 5 newly diagnosed patients were recruited. Among the R/R patients, 28 achieved CR or CRi. Two patients showed partial remission, and 9 patients did not respond. Among the 5 newly diagnosed patients, 4 achieved CR, and 1 achieved CRi. The median LFS and OS were 5.6 and 10.9 months, respectively. Prior Fms-like tyrosine kinase 3 (FLT3) inhibitor exposure (P = .007), 2 or more inductions (P = .001), and coexisting IDH2 (P = .008) and RUNX1 mutations (P = .003) were associated with lower CR/CRi rates. HSCT consolidation and deep molecular responses (defined as an FLT3-ITD variant allelic frequency [VAF] ≤ 0.1% or a nucleophosmin 1 [NPM1] mutant VAF ≤ 0.01%) were associated with better OS and LFS. Prior FLT3 inhibitor exposure and 2 or more inductions were associated with inferior LFS. CONCLUSIONS: SOME was safe and effective for R/R and newly diagnosed FLT3-ITD AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mepesuccinato de Omacetaxina/administração & dosagem , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Sorafenibe/administração & dosagem , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Éxons/genética , Feminino , Duplicação Gênica , Transplante de Células-Tronco Hematopoéticas , Mepesuccinato de Omacetaxina/efeitos adversos , Mepesuccinato de Omacetaxina/farmacocinética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Nucleofosmina , Indução de Remissão/métodos , Sorafenibe/efeitos adversos , Sorafenibe/farmacocinética , Transplante Homólogo , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/farmacocinética
12.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31665485

RESUMO

CONTEXT: The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. OBJECTIVE: To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. METHODS: Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. RESULTS: A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. CONCLUSIONS: In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.


Assuntos
Procedimentos Clínicos/normas , Agonistas de Dopamina/uso terapêutico , Hipofisectomia/métodos , Microcirurgia/métodos , Neoplasias Hipofisárias/terapia , Prolactinoma/terapia , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/normas , Feminino , Humanos , Hipofisectomia/efeitos adversos , Hipofisectomia/normas , Microcirurgia/efeitos adversos , Microcirurgia/normas , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/patologia , Guias de Prática Clínica como Assunto , Prolactina/metabolismo , Prolactinoma/patologia , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do Tratamento
13.
Lancet Gastroenterol Hepatol ; 5(1): 63-79, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31818473

RESUMO

Treatment strategies for inflammatory bowel disease (IBD) focus on the induction and long-term maintenance of deep remission to avoid complications of active disease and improve long-term outcomes. Medical therapies for IBD, notably the increasingly widespread use of biological therapy, are often effective at controlling disease, but these drugs are associated with substantial adverse events, which together with other factors-including increasing treatment costs and patient preferences-leads to concerns regarding indefinite use of medical therapy. Consequently, the need to consider the safety and feasibility of drug de-escalation once IBD remission has been achieved is clear. Here, we review the current evidence surrounding de-escalation of immunomodulator and biological therapy in Crohn's disease and ulcerative colitis. We discuss strategies for de-escalation, including the selection of patients who are appropriate for treatment de-escalation and the use of proactive drug monitoring, and review the evidence on subsequent optimal follow-up. We conclude by proposing an algorithm to guide de-escalation decisions, and highlight future perspectives, including the potential effect of emerging medication and personalised medicine for these diseases.


Assuntos
Terapia Biológica/métodos , Monitoramento de Medicamentos/métodos , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Indução de Remissão/métodos , Humanos
14.
World J Gastroenterol ; 25(39): 6025-6040, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660038

RESUMO

BACKGROUND: Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate) extracted from garlic, has proven activity against Helicobacter pylori (H. Pylori) infection. In recent years, clinical trials have explored its utility as an add-on therapy with variable outcomes reported. AIM: To perform a systemic review of allicin as an add-on treatment for H. Pylori infection and assess its efficacy in randomized controlled trials (RCTs). METHODS: Electronic databases including MEDLINE, EMBASE, the Web of Science, the Cochrane Database, the China National Knowledge Infrastructure Database, Chinese VIP Information Databases, Chinese Medical Databases, and the Wan-Fang Database were searched for keywords including "allicin", "Helicobacter pylori", "randomized clinical trials", and their synonyms. A meta-analysis was performed using the fixed-effects model for low heterogeneity and the random-effects model for high heterogeneity with sensitivity analysis. Bias was evaluated using Egger's tests. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the level of quality, and studies were classed as "high quality", "moderate quality", "low quality", and "very low quality". RESULTS: A total of eight RCTs consisting of 867 participants (435 from the allicin group and 432 from the control group) were included. Eradication rate in the allicin group (93.33%, 406/435) was significantly higher than that of the control group (83.56%, 361/432) [I 2 = 0%, odds ratio (OR) = 2.75, 95% confidence interval (CI): 1.74-4.35, P < 0.001]. The healing rate of ulcers following H. pylori therapy in the allicin group (86.17%, 349/405) was significantly higher than that of the control group (75.87%, 305/402) [I 2 = 0%, OR = 2.05, 95%CI: 1.39-3.03, P < 0.001]. The total remission rate of peptic ulcers across all allicin groups was 97.16%, which was significantly higher than that of controls [96.05% (389/405) vs 86.55% (360/402), I 2 = 0, OR = 3.04, 95%CI: 1.51-6.12, P = 0.015]. No significant differences in side effects were observed. TSA suggested that the trials were of sufficient standard to draw reliable conclusions. The quality of outcomes including eradication rates and side effects was graded as "very low" due to downgrades for "risk of bias" and "indirectness". Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as "low" due to downgrades for "risk of bias". CONCLUSION: Allicin as an add-on therapy improves H. pylori eradication, healing of ulcers, and remission of symptoms. These results are suggested to be treated with caution due to limited quality.


Assuntos
Anti-Infecciosos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Úlcera Gástrica/tratamento farmacológico , Ácidos Sulfínicos/administração & dosagem , Antiácidos/administração & dosagem , Antiácidos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Ensaios Clínicos como Assunto , Dissulfetos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Indução de Remissão/métodos , Úlcera Gástrica/microbiologia , Úlcera Gástrica/patologia , Ácidos Sulfínicos/efeitos adversos , Resultado do Tratamento
15.
Clin Cardiol ; 42(10): 899-907, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31339594

RESUMO

BACKGROUND: Vasospastic angina (VSA) is characterized by coronary spasm, which can be aggravated by vasoactive substances such as serotonin. Hypothesis Sarpogrelate, a selective serotonin receptor antagonist, and high-dose statin have some effects on the reduction of coronary spasm in patients with VSA. METHODS: We recruited 100 patients with angiographically confirmed VSA, and randomly assigned them into four groups: sarpogrelate with high-dose statin (Group A, n = 25), sarpogrelate with low-dose or no statin (Group B, n = 25), placebo with high-dose statin (Group C, n = 25), and placebo with low-dose or no statin (Group D, n = 25). The primary endpoint was the remission of coronary spasm on 1-year follow-up provocation test. RESULTS: The most common site of coronary spasm was left anterior descending artery (42%). Most patients (96%) took calcium channel blockers, and 46% were treated with vasodilators. Overall, 40% of patients reported no chest pain at 1 year, and 23% showed complete remission of coronary spasm on 1-year follow-up provocation test. No difference was observed in symptomatic and angiographically complete remission rate between the sarpogrelate and the placebo group. Although the apolipoprotein B level at the 1-year follow-up was significantly lower in the high-dose statin group, symptomatic and angiographic outcomes were not different according to statin intensity. Distal thrombolysis in myocardial infarction (TIMI) flow on initial provocation test was independently associated with angiographically complete remission. CONCLUSIONS: Sarpogrelate or high-dose statin did not significantly improve the angiographic remission rate in patients with VSA. Distal TIMI flow on initial provocation test could predict the complete remission of coronary spasm at follow-up.


Assuntos
Angina Pectoris/tratamento farmacológico , Vasoespasmo Coronário/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Succinatos/administração & dosagem , Adulto , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/etiologia , Angiografia Coronária , Vasoespasmo Coronário/complicações , Vasoespasmo Coronário/diagnóstico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Indução de Remissão/métodos , Antagonistas da Serotonina/administração & dosagem , Resultado do Tratamento , Adulto Jovem
16.
Intern Med ; 58(16): 2299-2304, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31118381

RESUMO

Objective Indigo naturalis (IN) is a traditional Chinese medicine that has recently been reported to be effective for ulcerative colitis (UC). The aim of this study was to evaluate the efficacy and safety of IN. Methods We performed a retrospective observational study for 14 patients with UC treated with IN from October 2015 to December 2016. Results After 8 weeks of oral administration of IN, the partial Mayo score decreased from 4 (2-5) to 1.5 (0-4) [median, interquartile range (IQR), p=0.015]. Among 10 active UC patients, 5 (50%) showed a clinical response, and 4 (40%) achieved clinical remission. Serial changes of endoscopic activity were evaluated in nine patients using the Mayo endoscopic subscore (MES), Rachmilewitz endoscopic index (REI), and UC endoscopy index of severity (UCEIS). The MES decreased from 2 (2-3) to 1 (1-2) [median (IQR), p=0.005], the REI decreased from 7 (5.5-11) to 3 (1-7) [median (IQR), p=0.008], and the UCEIS decreased from 3 (3-4.5) to 1 (0.5-3.5) [median (IQR), p=0.039]. One patient developed acute right-sided colitis with wall thickening and edematous change, and the remaining 13 showed no adverse events. Conclusion We conclude that IN is effective for patients with UC as a therapy for inducing remission.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Índigo Carmim/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
17.
J Med Case Rep ; 13(1): 80, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30846003

RESUMO

BACKGROUND: A case is reported of innocuous intestinal obstruction requiring surgical intervention that was confirmed to be Crohn's disease histopathologically in a resource-constrained rural mission hospital in Cameroon. CASE PRESENTATION: A 70-year man of Kumbo origin from Northwest region of Cameroon with a history of crampy right lower-quadrant abdominal pain, non-bloody, non-mucoid diarrhea alternating with constipation presented to my institution. Abdominal examination of the patient revealed an ill-defined mass in the right iliac fossa and visible peristalsis. An abdominal computed tomographic scan and barium enema study confirmed a complex ascending colonic and cecal tumor. The patient underwent exploratory laparotomy. The intraoperative finding was a huge complex inflammatory mass involving the cecum, terminal ileum, and sigmoid colon. He subsequently had sigmoidectomy with end-to-end sigmoidorectal anastomosis and a cecal resection, and the proximal ascending colon was exteriorized because end mucoid fistula and terminal ileostomy were performed. The histopathological diagnosis confirmed Crohn's disease. The patient subsequently received five courses of adjuvant chemotherapy consisting of azathioprine, methotrexate, mesalamine, and methylprednisolone. He had complete disease remission and subsequently had closure of ileostomy with satisfactory postoperative status. The most recent follow-up abdominal computed tomographic scan and colonoscopy revealed disease-free status. The patient is also currently receiving a maintenance dose of rectal mesalamine and oral omeprazole treatment. He has been followed every 2 months in the surgical outpatient clinic over the last 16 months with satisfactory clinical outcome. CONCLUSIONS: Crohn's disease is uncommon in Africa, and this entity is encountered sparingly. The signs and symptoms of Crohn's disease overlap with many other abdominal disorders, such as tuberculosis, ulcerative colitis, irritable bowel syndrome, and others. Several publications in the literature describe that it is difficult to make an accurate diagnosis of this disease, despite the fact that many diagnostic armamentaria are available to suggest its presence. Most of the patients with Crohn's disease are treated conservatively, and a few may require surgical intervention, especially those presenting with complications such as intestinal obstruction, perforations, and abscess as well as fistula formations, as seen in this index patient. Crohn's disease is considered by many to be a very rare disease in Africa. It is interesting to know that Crohn's disease, which affects mainly young adults, may debut at any age. The rarity and clinical curiosity of this entity suggested reporting of my patient's case. Evidence-based up-to-date information on Crohn's disease is also documented.


Assuntos
Doença de Crohn/diagnóstico , Obstrução Intestinal/patologia , Indução de Remissão/métodos , Dor Abdominal , Idoso , Camarões , Quimioterapia Adjuvante , Doença de Crohn/complicações , Doença de Crohn/terapia , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Laparotomia , Masculino , Resultado do Tratamento
18.
Community Ment Health J ; 55(4): 624-630, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30798451

RESUMO

The purpose of this cluster-randomized pilot effectiveness study was to compare two different group-based educational music therapy interventions with a control condition as measured by the stage model of recovery in adults on an acute care mental health unit. Participants (N = 69) were cluster-randomized to one of three single-session conditions: educational lyric analysis (ELA), educational songwriting (ESW), or control. ELA and ESW conditions targeted motivations for and factors contributing to recovery. Results indicated no significant between-group difference. However, ELA and ESW conditions tended to have slightly more favorable stage of recovery mean scores than the control condition. Generally, educational music therapy may be clinically relevant for impacting stage of recovery within the temporal parameters of a single session. As ELA and ESW conditions had similar results, the specific educational music therapy intervention did not affect results. Implications for clinical practice, limitations, and suggestions for future research are provided.


Assuntos
Transtornos Mentais/terapia , Musicoterapia , Adulto , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Musicoterapia/métodos , Unidade Hospitalar de Psiquiatria , Escalas de Graduação Psiquiátrica , Indução de Remissão/métodos , Resultado do Tratamento
19.
JAMA ; 321(2): 156-164, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644982

RESUMO

Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity. Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool. Design, Setting, and Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017. Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months. Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events. Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group. Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety. Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.


Assuntos
Colite Ulcerativa/terapia , Transplante de Microbiota Fecal , Adulto , Anaerobiose , Colonoscopia , Método Duplo-Cego , Enema , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Metaboloma , Pessoa de Meia-Idade , Indução de Remissão/métodos , Inquéritos e Questionários , Transplante Autólogo , Transplante Homólogo , Adulto Jovem
20.
Am J Med Sci ; 356(4): 350-356, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30360803

RESUMO

BACKGROUND: Ulcerative Colitis (UC) is characterized by chronic inflammation of the mucosal layers of the colon. Treatment of refractory UC is challenging and has a huge healthcare burden. Although there have been advancements in immunomodulatory therapies, these require a step-up financially, and these medications are also associated with significant adverse events. Curcumin, an active ingredient of turmeric, has been studied in the past and found to be useful in the treatment of UC when used as an adjuvant along with mesalamine. We did a systematic review and meta-analysis to explore the role curcumin plays in clinical and endoscopic remission in patients with UC. MATERIALS AND METHODS: A comprehensive literature review was conducted by first searching the MEDLINE, Pubmed, and Embase databases through December 2017 to identify all studies that compared the use of curcumin when used along with mesalamine with placebo for clinical and endoscopic improvement and remission. RESULTS: Three randomized controlled trials including 142 patients were included in the study. Use of curcumin along with mesalamine was associated with increased odds of clinical remission (pooled odds ratio of 6.78, 95% CI: 2.39-19.23, P = 0.042). Clinical improvement, endoscopic remission and improvement rate also trended higher in the curcumin group compared to placebo. CONCLUSIONS: This study demonstrates higher clinical remission rates when curcumin was used in combination with mesalamine to achieve remission in patients with UC. Curcumin, due to its cost effectiveness and safer side effect profile, can decrease the healthcare burden and morbidity associated with this relapsing and remitting disease.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Curcumina/uso terapêutico , Mesalamina/uso terapêutico , Indução de Remissão/métodos , Endoscopia , Humanos
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