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1.
Medicina (B Aires) ; 79(4): 315-321, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487255

RESUMO

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.


Assuntos
Aspirina/administração & dosagem , Benzodiazepinas/administração & dosagem , Clopidogrel/administração & dosagem , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Poliaminas/administração & dosagem , Quimioterapia Combinada , Humanos , Recidiva , Prevenção Secundária
2.
Anticancer Res ; 39(8): 4305-4314, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366522

RESUMO

BACKGROUND/AIM: Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated. PATIENTS AND METHODS: Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses. RESULTS: In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant. CONCLUSION: BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Náusea/epidemiologia , Vômito/epidemiologia , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/patologia , Fatores de Risco , Vômito/induzido quimicamente , Vômito/patologia
4.
Braz J Med Biol Res ; 52(8): e8519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389490

RESUMO

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.


Assuntos
Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Transplante de Fígado/efeitos adversos , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral
5.
Mem Inst Oswaldo Cruz ; 114: e190062, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389521

RESUMO

BACKGROUND: Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted. OBJECTIVES: This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection. METHODS: One hundred male Swiss albino mice were divided equally into five groups: healthy uninfected control (group I), infected control (group II), PZQ treated (group III), rimonabant (RIM) (SR141716, a CB1 receptor antagonist)-treated (group IV) and group V was treated with combined PZQ and RIM. Liver sections were obtained for histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining and assessment of CB1 receptor expression using real-time polymerase chain reaction (RT-PCR). FINDINGS: The most effective reduction in fibrotic marker levels and granuloma load was achieved by combined treatment with PZQ+RIM (group V): CB1 receptor expression (H = 26.612, p < 0.001), number of α-SMA-positive cells (F = 57.086, p < 0.001), % hepatic portal fibrosis (F = 42.849, p < 0.001) and number of granulomata (F = 69.088, p < 0.001). MAIN CONCLUSIONS: Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.


Assuntos
Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/parasitologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Rimonabanto/farmacologia , Esquistossomose/tratamento farmacológico , Actinas/análise , Animais , Anti-Helmínticos/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Quimioterapia Combinada , Granuloma/parasitologia , Granuloma/patologia , Imuno-Histoquímica , Cirrose Hepática/patologia , Masculino , Camundongos , Miofibroblastos/parasitologia , Miofibroblastos/patologia , Praziquantel/farmacologia , Reprodutibilidade dos Testes , Esquistossomose/patologia , Resultado do Tratamento
6.
Medicine (Baltimore) ; 98(32): e16357, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393344

RESUMO

Achieving and maintaining viral suppression in young adults (18-24 years) living with HIV is challenging. Overall HIV viral suppression rates are lower in young as compared to older adults. Longitudinal data provide valuable insight on dynamics of viral suppression and variables of potential influence on HIV virological failure (VF), but is scarce in young adults living with HIV on combination antiretroviral therapy (cART). We evaluated longitudinal virological outcomes of behaviorally young adults (18-24 years) living with HIV in the Netherlands over a period of 15 years.We analyzed data from the Dutch national HIV database of 816 young adults living with HIV on cART in the Netherlands from 2000 to 2015. VF was defined as 2 consecutive detectable plasma HIV-1 viral load (VL) measurements > 200 copies/ml. Generalized linear mixed model analyses were used to assess HIV VF over time and identify risk factors associated with VF.VF during the study follow-up occurred at least once in 26% of cases. The probability of experiencing VF decreased over the study period per calendar year (OR 0.78, 95% confidence interval [CI];0.72; 0.85). Factors significantly associated with VF were being infected through heterosexual contact (OR 5.20, CI 1.39;19.38) and originating from Latin America or the Caribbean (OR 6.59, CI 2.08;20.92). Smaller, yet significant risk factors for VF were being infected through a blood transfusion or a needle accident (OR9.93, CI 1.34;73.84, and having started with cART with a nadir CD4 count >500 cells/µl (OR 11.36, CI 2.03;63.48).In our large cohort of young adults, the risk of VF has diminished over 15 years. Specific subgroups were identified to be at risk for suboptimal treatment.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Antirretrovirais/administração & dosagem , Contagem de Linfócito CD4 , Grupos de Populações Continentais , Quimioterapia Combinada , Feminino , Infecções por HIV/etiologia , HIV-1 , Humanos , Estudos Longitudinais , Masculino , Países Baixos , Fatores de Risco , Comportamento Sexual , Falha de Tratamento , Carga Viral , Adulto Jovem
7.
Medicine (Baltimore) ; 98(32): e16813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393412

RESUMO

Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/µL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/µL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/µL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/economia , Contagem de Linfócito CD4 , Análise Custo-Benefício , Quimioterapia Combinada , Farmacoeconomia , Honorários Farmacêuticos/estatística & dados numéricos , Feminino , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/economia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
8.
Medicine (Baltimore) ; 98(33): e16878, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415429

RESUMO

BACKGROUND: Guizhi Fuling pill, a famous traditional Chinese herbal formula, has been widely used for treatment of gynecological diseases. This meta-analysis sought to evaluate the add-on effect of Guizhi Fuling capsule (GZFL) to mifepristone in women with endometriosis. METHODS: A comprehensively literature search was conducted using Pubed, Embase, Cochrane Library, Wanfang, CNKI, VIP databases from their inceptions to January 25, 2019. Randomized controlled trials that compared GZFL plus mifepristone to mifepristone alone for treatment of endometriosis were eligible. Main outcomes were pregnancy, reduction of the recurrence, and serum level of follicle-stimulating hormone, luteinizing hormone, estradiol or progesterone. RESULTS: A total of 1052 women with endometriosis from 10 trials were identified and analyzed. Meta-analyses showed that GZFL plus mifepristone was superior to mifepristone in reducing the recurrence of endometriosis (RR 0.40; 95% CI 0.27-0.59) and improving the pregnancy (risk ratio [RR] 1.74; 95% confidence intervals [CI] 1.40-2.17). Moreover, adjuvant treatment with GZFL also significantly reduced serum level of estradiol (mean difference [MD] -20.83 pmol/L; 95% CI -34.01 to -7.65) and progesterone (MD -0.18 mmol/L; 95% CI -0.23 to -0.12). However, there were no significant differences in serum level of follicle-stimulating hormone (MD -0.42 U/L; 95% CI -1.16 to 0.31) and luteinizing hormone (MD -0.04 U/L; 95% CI -0.43 to 0.34). CONCLUSION: GZFL as adjuvant therapy to mifepristone appears to have additional benefits in preventing recurrence of endometriosis and improving pregnancy among women with endometriosis. However, these conclusions should be interpreted with caution due to the methodological flaws of the included trials.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Endometriose/tratamento farmacológico , Mifepristona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Arch Endocrinol Metab ; 63(4): 328-336, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365632

RESUMO

OBJECTIVE: Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. SUBJECTS AND METHODS: Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. RESULTS: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. CONCLUSIONS: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.


Assuntos
Acromegalia/tratamento farmacológico , Cabergolina/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Receptores de Somatostatina/uso terapêutico , Adenoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Brasil , Cabergolina/administração & dosagem , Criança , Quimioterapia Combinada , Feminino , Hormônio do Crescimento/sangue , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptores de Somatostatina/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Arch Endocrinol Metab ; 63(4): 320-327, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31460622

RESUMO

OBJECTIVE: To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. SUBJECTS AND METHODS: We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. RESULTS: Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). CONCLUSION: this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7.


Assuntos
Acromegalia/tratamento farmacológico , Cabergolina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Somatostatina/análogos & derivados , Adulto , Idoso , Argentina , Cabergolina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
11.
JAMA ; 322(7): 622-631, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429896

RESUMO

Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent. Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017. Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline. Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c). Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016). Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Olanzapina/uso terapêutico , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/efeitos adversos , Modelos de Riscos Proporcionais , Prevenção Secundária , Sertralina/uso terapêutico , Adulto Jovem
12.
Arq Gastroenterol ; 56(2): 184-190, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31460584

RESUMO

BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.


Assuntos
Acetilcisteína/administração & dosagem , Metformina/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ácido Ursodesoxicólico/administração & dosagem , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
13.
Zhonghua Nei Ke Za Zhi ; 58(8): 596-598, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31365982

RESUMO

To explore how to diagnose and treat brucellosis accurately and timely in patients with fever of unkown origin in non-pastoral areas. The epidemiological history, clinical symptoms, complete blood counts, procalcitonin and treatment efficacy of 7 patients with brucellosis were analyzed retrospectively. Some characteristic manifestations should be differentiated from tuberculosis. The clinical symptoms were relieved after combination of doxycycline, rifampicin, levofloxacin and amikacin for 6 weeks, only one patient with bone destruction needed orthopedic surgery. The overall response rate was 6/7. No relapse occurred during half year follow-up.


Assuntos
Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Brucelose/diagnóstico , Brucelose/tratamento farmacológico , Doxiciclina/uso terapêutico , Levofloxacino/uso terapêutico , Rifampina/uso terapêutico , Doença Aguda , Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Humanos , Levofloxacino/administração & dosagem , Pró-Calcitonina , Estudos Retrospectivos , Rifampina/administração & dosagem , Resultado do Tratamento
14.
Asia Pac J Ophthalmol (Phila) ; 8(4): 280-284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31369405

RESUMO

PURPOSE: The aim of this study was to provide a retrospective analysis of the presentation, demographics, and treatment regimens for ocular toxoplasmosis at a large tertiary referral uveitis center. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 48 patients with ocular toxoplasmosis who presented to Sydney Eye Hospital participated in this study. METHODS: This is a retrospective review of patient files who presented to Sydney Eye Hospital between 2007 and 2016 with clinical features consistent with ocular toxoplasmosis. Baseline risk factors and treatment details were recorded and analyzed. Main outcome measures were visual acuity and relapse rate compared with other studies in ocular toxoplasmosis. RESULTS: The median age was 35.5 (interquartile range 21-50) with 30 (60%) patients having no previous symptomatic episodes or evidence of chorioretinal scarring. Visual acuity at presentation was 0.51 or 6/19 (SE 0.096) and at follow-up 0.31 or 6/12 (SE 0.094). Nine patients experienced a recurrence during the period of observation with median time to recurrence 2.2 years (SE 0.45) and the relapse rate was 0.09/person-years. Location of lesion was predominantly within the vascular arcades (n = 44) with macular involvement in 9 patients. Most patients received clindamycin therapy (n = 34) with pyrimethamine and sulfadiazine was used for those with macula involvement. CONCLUSIONS: Patients with ocular toxoplasmosis had fewer recurrences compared with other published series and had better visual recovery. The majority of patients received clindamycin and oral prednisolone which were well tolerated with pyrimethazine and sulfadiazine reserved for those with macula-involving disease.


Assuntos
Anti-Infecciosos/administração & dosagem , Infecções Oculares Parasitárias/diagnóstico , Glucocorticoides/administração & dosagem , Centros de Atenção Terciária , Toxoplasmose Ocular/diagnóstico , Acuidade Visual , Administração Oral , Adulto , Anticorpos Antiprotozoários/análise , Austrália/epidemiologia , DNA de Protozoário/análise , Quimioterapia Combinada , Infecções Oculares Parasitárias/tratamento farmacológico , Infecções Oculares Parasitárias/epidemiologia , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/tratamento farmacológico , Toxoplasmose Ocular/epidemiologia , Adulto Jovem
15.
Medicine (Baltimore) ; 98(32): e16682, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393368

RESUMO

Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control.A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded.The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ±â€Š20.7 mg/day to 55.0 ±â€Š11.1 mg/day after 2-week treatment, and to 3.3 ±â€Š2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment.Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients' conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Metotrexato/administração & dosagem , Doença de Still de Início Tardio/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Antirreumáticos/farmacologia , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Resultado do Tratamento
17.
Anticancer Res ; 39(7): 3303-3309, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262850

RESUMO

Combination therapies are used in the clinic to achieve cure, better efficacy and to circumvent resistant disease in patients. Initial assessment of the effect of such combinations, usually of two agents, is frequently performed using in vitro assays. In this review, we give a short summary of the types of analyses that were presented during the Preclinical and Early-phase Clinical Pharmacology Course of the Pharmacology and Molecular Mechanisms Group, European Organization for Research and Treatment on Cancer, that can be used to determine the efficacy of drug combinations. The effect of a combination treatment can be calculated using mathematical equations based on either the Loewe additivity or Bliss independence model, or a combination of both, such as Chou and Talalay's median-drug effect model. Interactions can be additive, synergistic (more than additive), or antagonistic (less than additive). Software packages CalcuSyn (also available as CompuSyn) and Combenefit are designed to calculate the extent of the combined effects. Interestingly, the application of machine-learning methods in the prediction of combination treatments, which can include pharmacogenomic, genetic, metabolomic and proteomic profiles, might contribute to further refinement of combination regimens. However, more research is needed to apply appropriate rules of machine learning methods to ensure correct predictive models.


Assuntos
Combinação de Medicamentos , Quimioterapia Combinada , Animais , Interações de Medicamentos , Humanos , Farmacologia Clínica , Pesquisa Médica Translacional
19.
Medicine (Baltimore) ; 98(26): e16065, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261514

RESUMO

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Some clinical trials have demonstrated that apatinib is efficacious against advanced nonsquamous NSCLC. OBJECTIVE: This study aimed to probe efficacy and safety of apatinib plus docetaxel, as the second or above line treatment, in advanced nonsquamous NSCLC. DESIGN: Multicenter, prospective, single arm study. SETTING: Three teaching hospitals centers in the Sichuan. PARTICIPANTS: Fourteen patients with stage IVA/B nonsquamous NSCLC had previously received at least 1 platinum-based chemotherapy regimen. INTERVENTION: Patients who were enrolled between November 2016 and January 2018 were given docetaxel (75 mg/m, i.v., d1) plus oral apatinib (250 mg/d), 4 weeks as one cycle, until disease progression or intolerance to adverse events (AE). MAIN OUTCOME MEASURES: The primary endpoint was progression-free survival (PFS). The secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), overall survival (OS), and AE incidence rate. RESULTS: All patients carried adenocarcinoma by pathological type. The median follow-up duration was 9.76 months. Out of 14 cases, 12 were evaluable, showing ORR of 33.33%, DCR of 66.67%, DCR of 50% in cases with brain metastasis, median PFS of 2.92 months (95% CI: 1.38-4.48), and 6-month OS of 80%. Primary AEs encompassed: leukopenia in 7 cases (58.33%), hand-foot skin reaction in 5 cases (41.67%), and diarrhea in 4 cases (33.33%). Among them, grade 3 AEs were: leukopenia in 4 cases (33.33%), and hand-foot skin reaction in 1 case (8.33%). No grade 4/5 AEs were reported. Univariate and multivariate analysis were conducted respectively for PFS and OS. These factors encompassed: gender, age, gene mutations, clinical stage, ECOG scores, quantity of metastatic foci, brain metastasis, and hand-foot skin reaction. Results demonstrated zero risk factors for PFS or OS. CONCLUSION: Apatinib plus docetaxel, as the second or above line treatment, is effective and safe against advanced nonsquamous NSCLC, with good tolerance profile. TRIAL REGISTRATION: NCT03416231.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Progressão da Doença , Docetaxel/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/efeitos adversos , Retratamento , Análise de Sobrevida , Resultado do Tratamento , Moduladores de Tubulina/efeitos adversos , Moduladores de Tubulina/uso terapêutico
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